Accumulation of scandium in plasma in patients with chronic renal failure.

Scandium (Sc) is an element with many industrial applications, but relatively little is known about its physiological and/or toxicological effects, and very little data are available concerning the role of Sc in chronic renal failure (CRF). This paper examines the changes in plasma levels of Sc in predialysis patients with CRF and the relationship with blood parameters. The participants in this trial were 48 patients with CRF in predialysis and 53 healthy controls. Erythrocyte, haemoglobin, and haematocrit counts in blood were determined, and levels of creatinine, urea, uric acid, albumin, total protein and Sc were measured in plasma. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients were found to have higher plasma levels of creatinine, urea, uric acid, albumin, total protein, and Sc and a lower GFR than that the controls. Scandium in plasma was positively correlated with creatinine and plasma urea and negatively correlated with GFR, haemoglobin, and haematocrit and was associated with the risk of lower levels of erythrocytes, haemoglobin, and haematocrit. CRF was associated with increases in the circulating levels of scandium.

Rationale and design of a randomized, double-blind, placebo controlled multicenter trial to study efficacy, security, and long term effects of intermittent repeated levosimendan administration in patients with advanced heart failure: LAICA study.

BACKGROUND Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation. METHODS The LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 μg/kg/min dose, without a loading dose, every 30 days, or placebo. RESULTS The main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events. CONCLUSIONS The LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Phlebotomine fauna, natural infection rate and feeding habits of Lutzomyia cruzi in Jaciara, state of Mato Grosso, Brazil

Visceral leishmaniasis (VL) in Brazil is transmitted by the phlebotomine Lutzomyia longipalpis and in some midwestern regions by Lutzomyia cruzi. Studies of the phlebotomine fauna, feeding habits and natural infection rate by Leishmania contribute to increased understanding of the epidemiological chain of leishmaniases and their vectorial capacity. Collections were performed in Jaciara, state of Mato Grosso from 2010-2013, during which time 2,011 phlebotomines (23 species) were captured (68.70% Lu. cruzi and 20.52% Lutzomyia whitmani). Lu. cruzi females were identified by observing the shapes of the cibarium (a portion of the mouthpart) and spermatheca, from which samples were obtained for polymerase chain reaction to determine the rates of natural infection. Engorged phlebotomines were assessed to identify the blood-meal host by ELISA. A moderate correlation was discovered between the number of Lu. cruzi and the temperature and the minimum rate of infection was 6.10%. Twenty-two females were reactive to the antisera of bird (28%), dog (3.30%) and skunk (1.60%). We conclude that Lu. cruzi and Lu. whitmani have adapted to the urban environment in this region and that Lu. cruzi is the most likely vector of VL in Jaciara. Moreover, maintenance of Leishmania in the environment is likely aided by the presence of birds and domestic and synanthropic animals.

Influence of gender on long-term prognosis of patients with chronic heart failure seen in heart failure clinics.

BACKGROUND Controversy exists concerning the influence of gender in the prognosis of patients with heart failure and no evidence is available from specific heart failure clinics. HYPOTHESIS Women with ambulatory heart failure are managed differently than men, although their prognosis might be better than men. METHODS AND RESULTS We analyzed the clinical characteristics, complementary test results, treatment, and prognosis in 4720 patients with chronic heart failure seen in 62 specialized clinics forming part of a multicenter registry during a mean follow-up of 40 months. The mean age was 65 +/- 12 years and 71% were men. The men were younger than the women and more often had a history of hyperlipidemia and ischemic heart disease. The men had a more advanced heart failure New York Heart Association (NYHA) functional class (III-IV) than the women and a greater frequency of systolic ventricular dysfunction. The men more often received treatment with beta-blockers, vasodilators, and antiplatelet aggregators as well as higher mean doses as compared with the women. The overall survival after the follow-up was similar for both genders, although the women had lower rates of survival free of admission for heart failure. CONCLUSIONS Despite the mortality of women and men with heart failure being similar, the rate of readmission for heart failure is greater in women in specialized heart failure clinics. These results may be associated with the pharmacological treatment differences observed.

Progression rate of self-propelled feeding tubes in critically ill patients.

OBJECTIVE: Gaining postpyloric access in ventilated, sedated ICU patients usually requires time-consuming procedures such as endoscopy. Recently, a feeding tube has been introduced that migrates spontaneously into the jejunum in surgical patients. The study aimed at assessing the rate of migration of this tube in critically ill patients. DESIGN: Prospective descriptive trial. SETTING: Surgical ICU in a tertiary University Hospital. PATIENTS: One hundred and five consecutive surgical ICU patients requiring enteral feeding were enrolled, resulting in 128 feeding-tube placement attempts. METHODS: A self-propelled tube was used and followed up for 3 days: progression was assessed by daily contrast-injected X-ray. Severity of illness was assessed with SAPS II and organ failure assessed with SOFA score. RESULTS: The patients were aged 55+/-19 years (mean+/-SD) with SAPS II score of 45+/-18. Of the 128 tube placement attempts, 12 could not be placed in the stomach; eight were accidentally pulled out while in gastric position due to the necessity to avoid fixation during the progression phase. Among organ failures, respiratory failure predominated, followed by cardiovascular. By day 3, the postpyloric progression rate was 63/128 tubes (49%). There was no association between migration and age, or SAPS II score, but the progression rate was significantly poorer in patients with hemodynamic failure. Use of norepinephrine and morphine were negatively associated with tube progression (P<0.001), while abdominal surgery was not. In ten patients, jejunal tubes were placed by endoscopy. CONCLUSION: Self-propelled feeding tubes progressed from the stomach to the postpyloric position in 49% of patients, reducing the number of endoscopic placements: these tubes may facilitate enteral nutrient delivery in the ICU.

Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy.

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.

Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study.

BACKGROUND: The race- and sex-specific epidemiology of incident heart failure (HF) among a contemporary elderly cohort are not well described. METHODS: We studied 2934 participants without HF enrolled in the Health, Aging, and Body Composition Study (mean [SD] age, 73.6 [2.9] years; 47.9% men; 58.6% white; and 41.4% black) and assessed the incidence of HF, population-attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF. RESULTS: During a median follow-up of 7.1 years, 258 participants (8.8%) developed HF (13.6 cases per 1000 person-years; 95% confidence interval, 12.1-15.4). Men and black participants were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (PAR, 23.9% for white participants and 29.5% for black participants) and uncontrolled blood pressure (PAR, 21.3% for white participants and 30.1% for black participants) carried the highest PAR in both races. Among black participants, 6 of 8 risk factors assessed (smoking, increased heart rate, coronary heart disease, left ventricular hypertrophy, uncontrolled blood pressure, and reduced glomerular filtration rate) had more than 5% higher PAR compared with that among white participants, leading to a higher overall proportion of HF attributable to modifiable risk factors in black participants vs white participants (67.8% vs 48.9%). Participants who developed HF had higher annual mortality (18.0% vs 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher among black participants (62.1 vs 30.3 hospitalizations per 100 person-years, P < .001). CONCLUSIONS: Incident HF is common in older persons; a large proportion of HF risk is attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be considered in prevention and treatment efforts.

Hormonal, global, and regional haemodynamic responses to a vascular antagonist of vasopressin in patients with congestive heart failure with and without hyponatraemia.

The pathophysiological role of an increase in circulating vasopressin in sustaining global and regional vasoconstriction in patients with congestive heart failure has not been established, particularly in patients with hyponatraemia. To assess this further, 20 patients with congestive heart failure refractory to digoxin and diuretics were studied before and 60 minutes after the intravenous injection (5 micrograms/kg) of the vascular antagonist of vasopressin [1(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(0-methyl) tyrosine] arginine vasopressin. Ten patients were hyponatraemic (plasma sodium less than 135 mmol/l) and 10 were normonatraemic. In both groups of patients the vascular vasopressin antagonist did not alter systemic or pulmonary artery pressures, right atrial pressure, pulmonary capillary wedge pressure, cardiac index, or vascular resistances. Furthermore, there was no change in skin and hepatic blood flow in either group after the injection of the vascular antagonist. Only one patient in the hyponatraemic group showed considerable haemodynamic improvement. He had severe congestive heart failure and a high concentration of plasma vasopressin (51 pmol/l). Plasma renin activity, vasopressin, or catecholamine concentrations were not significantly changed in response to the administration of the vasopressin antagonist in either the hyponatraemic or the normonatraemic groups. Patients with hyponatraemia, however, had higher baseline plasma catecholamine concentrations, heart rate, pulmonary pressure and resistance, and lower hepatic blood flow than patients without hyponatraemia. Plasma vasopressin and plasma renin activity were slightly, though not significantly, higher in the hyponatraemic group. Thus the role of vasopressin in sustaining regional or global vasoconstriction seems limited in patients with congestive heart failure whether or not concomitant hyponatraemia is present. Vasopressin significantly increases the vascular tone only in rare patients with severe congestive heart failure and considerably increased vasopressin concentrations. Patients with hyponatraemia do, however, have raised baseline catecholamine concentrations, heart rate, pulmonary arterial pressure and resistance, and decreased hepatic blood flow.

Clinical characteristics and outcome of patients admitted to a medico-surgical ICU requiring non invasive ventilation (NIV) for hypercapnic respiratory failure

Introduction: Because it decreases intubation rate and mortality, NIV has become first-line treatment in case of hypercapnic respiratory failure (HRF). Whether this approach is equally successful for all categories of HRF patients is however debated. We assessed if any clinical characteristics of HRF patients were associated with NIV intensity, success, and outcome, in order to identify prognostic factors. Methods: Retrospective analysis of the clinical database (clinical information system and MDSi) of patients consecutively admitted to our medico-surgical ICU, presenting with HRF (defined as PaCO2 >50 mm Hg), and receiving NIV between January 2009 and December 2010. Demographic data, medical diagnoses (including documented chronic lung disease), reason for ICU hospitalization, recent surgical interventions, SAPS II and McCabe scores were extracted from the database. Total duration of NIV and the need for tracheal intubation during the 5 days following the first hypercapnia documentation, as well as ICU and hospital mortality were recorded. Results are reported as median [IQR]. Comparisons with Chi2 or Kruskal-Wallis tests, p <0.05 (*). Results: 164 patients were included, 45 (27.4%) of whom were intubated after 10 [2-34] hours, after having received 7 [2-19] hours of NIV. NIV successful patients received 15 [5-22] hours of NIV for up to 5 days. Intubation was correlated with increased ICU (20% vs. 3%, p <0.001) and hospital (46.7% vs. 30.2, p >0.05) mortality. Conclusions: A majority of patients requiring NIV for hypercapnic respiratory failure in our ICU have no diagnosed chronic pulmonary disease. These patients tend to have increased ICUand hospital mortality. The majority of patients were non-surgical, a feature correlated with increased hospital mortality. Beside usual predictors of severity such as age and SAPS II, absence of diagnosed chronic pulmonary disease and non-operative state appear to be associated with increased mortality. Further studies should explore whether these patients are indeed more prone to an adverse outcome and which therapeutic strategies might contribute to alter this course.

Analysis of past and future dam formation and failure in the Santa Cruz River (San Juan province, Argentina)

Around 11.5 * 106 m3 of rock detached from the eastern slope of the Santa Cruz valley (San Juan province, Argentina) in the first fortnight of January 2005. The rockslide?debris avalanche blocked the course, resulting in the development of a lake with maximum length of around 3.5 km. The increase in the inflow rate from 47,000?74,000 m3/d between April and October to 304,000 m3/d between late October and the first fortnight of November, accelerated the growing rate of the lake. On 12 November 2005 the dam failed, releasing 24.6 * 106 m3 of water. The resulting outburst flood caused damages mainly on infrastructure, and affected the facilities of a hydropower dam which was under construction 250 km downstream from the source area. In this work we describe causes and consequences of the natural dam formation and failure, and we dynamically model the 2005 rockslide?debris avalanche with DAN3D. Additionally, as a volume ~ 24 * 106 m3of rocks still remain unstable in the slope, we use the results of the back analysis to forecast the formation of a future natural dam. We analyzed two potential scenarios: a partial slope failure of 6.5 * 106 m3 and a worst case where all the unstable volume remaining in the slope fails. The spreading of those potential events shows that a new blockage of the Santa Cruz River is likely to occur. According to their modeled morphometry and the contributing watershed upstream the blockage area, as the one of 2005, the dams would also be unstable. This study shows the importance of back and forward analysis that can be carried out to obtain critical information for land use planning, hazards mitigation, and emergency management.

The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis.

The efficacy of treatments for osteoporosis does not become evident when evaluated by fracture incidence (FI). Vertebral FI decreased in all controlled studies on calcitonin, but not significantly. Small sample sizes and short periods of treatment may have masked a possible therapeutic benefit, but longer, controlled studies with sodium fluoride or etidronate in larger groups of patients also failed to show a decrease in FI. The present analysis of nine published, therapeutic studies which indicate the FI per year and the initial prevalence of vertebral fractures, examines the question of whether the initial prevalence of fractures has an effect on the subsequent incidence of new fractures and whether the therapeutic effects have to be evaluated as a function of the initial prevalence of fractures. Bearing in mind the differences in roentgenological evaluation and in the size and quality of the various studies, the analysis revealed (1) that in the control groups there was a higher FI in patients with more than three vertebral fractures at baseline (estimated odds ratio (OR) = 49, p = 0.011); (2) that a similar trend, although not statistically significant, was observed in treated patients; (3) that the groups of control patients treated for more than 1 year showed in general an increase in FI beyond the first year and that the reverse was true in treated patients. In conclusion, failure to allow for the initial prevalence of vertebral fractures at the individual level in therapeutic trials of calcitonin to treat osteoporosis and prevent new fractures might have contributed to the absence of a demonstrable benefit of the treatment in those studies.

Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula.

The most widely used formula for estimating glomerular filtration rate (eGFR) in children is the Schwartz formula. It was revised in 2009 using iohexol clearances with measured GFR (mGFR) ranging between 15 and 75 ml/min × 1.73 m(2). Here we assessed the accuracy of the Schwartz formula using the inulin clearance (iGFR) method to evaluate its accuracy for children with less renal impairment comparing 551 iGFRs of 392 children with their Schwartz eGFRs. Serum creatinine was measured using the compensated Jaffe method. In order to find the best relationship between iGFR and eGFR, a linear quadratic regression model was fitted and a more accurate formula was derived. This quadratic formula was: 0.68 × (Height (cm)/serum creatinine (mg/dl))-0.0008 × (height (cm)/serum creatinine (mg/dl))(2)+0.48 × age (years)-(21.53 in males or 25.68 in females). This formula was validated using a split-half cross-validation technique and also externally validated with a new cohort of 127 children. Results show that the Schwartz formula is accurate until a height (Ht)/serum creatinine value of 251, corresponding to an iGFR of 103 ml/min × 1.73 m(2), but significantly unreliable for higher values. For an accuracy of 20 percent, the quadratic formula was significantly better than the Schwartz formula for all patients and for patients with a Ht/serum creatinine of 251 or greater. Thus, the new quadratic formula could replace the revised Schwartz formula, which is accurate for children with moderate renal failure but not for those with less renal impairment or hyperfiltration.

Failure of the surgical treatment in 115 infected hip arthroplasties-­analysis of a 12-­year prosthetic joint cohort study (1999-­2010)

Background:¦Infection after total or partial hip arthroplasty (HA) leads to significant long-­term morbidity and high healthcare cost. We evaluated reasons for treatment failure of different surgical modalities in a 12-­year prosthetic hip joint infection cohort study.¦Method:¦All patients hospitalized at our institution with infected HA were included either retrospectively (1999-­‐2007) or prospectively¦(2008-­‐2010). HA infection was defined as growth of the same microorganism in ≥2 tissues or synovialfluid culture, visible purulence, sinus tract or acute inflammation on tissue histopathology. Outcome analysis was performed at outpatient visits, followed by contacting patients, their relatives and/or treating physicians afterwards.¦Results:¦During the study period, 117 patients with infected HA were identified. We excluded 2 patients due to missing data. The average age was 69 years (range, 33-­‐102 years); 42% were female. HA was mainly performed for osteoarthritis (n=84), followed by trauma (n=22), necrosis (n=4), dysplasia(n=2), rheumatoid arthritis (n=1), osteosarcoma (n=1) and tuberculosis (n=1). 28 infections occurred early(≤3 months), 25 delayed (3-­‐24 months) and 63 late (≥24 months after surgery). Infected HA were¦treated with (i) two-­‐stage exchange in 59 patients (51%, cure rate: 93%), (ii) one-­‐stage exchange in 5 (4.3%, cure rate: 100%), (iii) debridement with change of mobile parts in 18 (17%, cure rate: 83%), (iv) debridement without change of mobile¦parts in 17 (14%, cure rate : 53% ), (v) Girdlestone in 13 (11%, cure rate: 100%), and (vi) two-­‐stage exchange followed by¦removal in 3 (2.6%). Patients were followed for an average of 3.9 years (range, 0.1 to 9 years), 7 patients died unrelated to the infected HA. 15 patients (13%) needed additional operations, 1 for mechanical reasons(dislocation of spacer) and 14 for persistent infection: 11 treated with debridement and retention (8 without change; and 3 with change of mobile parts) and 3 with two-­‐stage exchange. The average number of surgery was 2.2 (range, 1 to 5). The infection was finally eradicated in all patients, but the functional outcome remained unsatisfactory in 20% (persistent pain or impaired mobility due to spacer or Girdlestone situation).¦Conclusions:¦Non-­‐respect of current treatment concept leads to treatment failure with subsequent operations. Precise analysis of each treatment failure can be used for improving the treatment algorithm leading to better results.

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Failure of surgical treatment in 115 infected total hip arthroplasties - analysis of a 12-year prosthetic joint cohort study (1999-2010)

Infection of total hip arthroplasties (THA) leads to significant long-termmorbidity and high healthcare costs. We evaluated the differentreasons for treatment failure using different surgical modalities in a12-year prosthetic joint infection cohort study.Method: All patients hospitalized at our institution with infected THAwere included either retrospectively (1999-2007) or prospectively(2008-2010). THA infection was defined as growth of the same microorganismin ≥2 tissue or synovial fluid culture, visible purulence, sinustract or acute inflammation on tissue histopathology. Outcome analysiswas performed at outpatient visits, followed by contacting patients,their relatives and/or treating physicians afterwards.Results: During the study period, 117 patients with THA were identified.We exclude 2 patients due to missing data. The median age was69 years (range, 33-102 years); 42% were women. THA was mainlyperformed for osteoarthritis (n = 84), followed by trauma (n = 22),necrosis (n = 4), dysplasia (n = 2), rheumatoid arthritis (n = 1), osteosarcoma(n = 1) and tuberculosis (n = 1). 28 infections occurred early(≤3 months), 25 delayed (3-24 months) and 63 late (≥24 months aftersurgery). Infected THA were treated with (i) two-stage exchange in59 patients (51%, cure rate: 93%), (ii) one-stage exchange in 5 (4.3%,cure rate: 100%), (iii) debridement with change of mobile parts in18 (17%, cure rate: 83%), (iv) debridement without change of mobileparts in 17 (14%, cure rate: 53% ), (v) Girdlestone in 13 (11%, curerate: 100%), and (vi) two-stage exchange followed by removal in 3(2.6%). Patients were followed for a mean of 3.9 years (range, 0.1 to 9years), 7 patients died unrelated to the infected THA. 15 patients (13%)needed additional operations, 1 for mechanical reasons (dislocationof spacer) and 14 for persistent infection: 11 treated with debridementand retention (8 without change and 3 with change of mobile parts)and 3 with two-stage exchange. The mean number of surgery was 2.2(range, 1 to 5). The infection was finally eradicated in all patients, butthe functional outcome remained unsatisfactory in 20% (persistentpain or impaired mobility due to spacer or Girdlestone situation).Conclusions: Non-respect of current treatment concept leads totreatment failure with subsequent operations. Precise analysis of eachtreatment failures can be used for improving the treatment algorithmleading to better results.