Outpatient parenteral antimicrobial therapy for infective endocarditis in patients over 80 years.

OBJECTIVE: The incidence of infective endocarditis is progressively increasing, especially in elderly patients. Outpatient parenteral antibiotic therapy (OPAT) is being an excellent alternative for treatment, but advanced age is one of the relative contraindications. The aim of this study is to compare the characteristics and prognosis of patients less or more than 80 years, treated with OPAT. METHODS: One hundred and ninety four patients were included between 1996 and 2015, 31 of them older than 80 years. RESULTS: The most frequently affected valve is the aortic one, mainly native valves. Most used antibiotics are ceftriaxone, ampicillin, cloxacillin and daptomycin. Differences in surgery (39.9% vs 9.7%, p=0.001) and use of infusion pump (55.2% vs 35.5%; p= 0.044) were observed, under 80 years and older respectively. No differences in readmissions and mortality were observed. CONCLUSIONS: OPAT could be considered an effective alternative for appropriately-selected elderly patients with infective endocarditis.

Influence of antiviral therapy in the long-term outcome of recurrent hepatitis C virus infection following liver transplantation.

INTRODUCTION: Severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients (LTR) is variable and the influence of different factors, including the administration of antiviral therapy in the long-term outcome is controversial. METHODS: We analyzed the outcome of a cohort of HCV-infected LTR who were transplanted in our institution. Patients were divided into 2 groups (severe and non-severe HCV disease) depending on the presence of a fibrosis score of F ≥ 2 in the Scheuer index and/or fibrosing cholestasic hepatitis (FCH) in a graft biopsy. Risk factors were studied using logistic regression analysis. Survival of patients was estimated using Kaplan-Meier plots. A total of 146 patients were followed for a mean of 58 months. RESULTS: Fifty-six (34%) patients developed severe HCV disease and showed shorter survival (P < 0.024). Donor age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06) and pre-transplant viral load (VL) >10(6) UI/mL (OR: 3.5; 95% CI: 1.42-10.61) were the only factors associated with severe HCV infection. Over-immunosuppression (OR: 2.3; 95% CI: 1.2-4.41) was specifically associated with the development of FCH. Overall, patient survival in recipients who received a full course of anti-HCV therapy was higher than in patients who did not complete antiviral therapy (P = 0.004) or received no treatment (P = 0.007). Patients with non-severe HCV infection have a higher probability of receiving a full course of antiviral therapy (P = 0.033). CONCLUSION: In conclusion, donor age, pre-transplant VL, and over-immunosuppression were associated with the long-term development of severe HCV recurrence in liver grafts. Administration of a full course of antiviral therapy was associated with better survival.

Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments in the Valencia region, Spain. The baseline characteristics of the ESOSVAL cohort.

UNLABELLED: This study provides information on the prevalence of the most important risk factors for osteoporosis and osteoporotic fracture in a large sample of women and men from the Valencia region and also provides the FRAX 10-year major and hip fracture risks for this population, as well as data about the use of diagnostic tests and antiosteoporotic treatments. INTRODUCTION: The purpose of this study was to describe demographic characteristics, osteoporosis risk factors, the 10-year risk of osteoporotic fracture, and the use of densitometry and antiosteoporotic treatments in the Valencia region, Spain. METHODS: A cross-sectional study using the ESOSVAL cohort baseline data was conducted. We analyze the data from 5,310 women and 5,725 men aged 50 and over who attended to 272 collaborating primary care centers in 2009-2010. We collected the demographic, anthropometric, clinical, and pharmacy data from the electronic medical record. RESULTS: The mean age of participants was 64.3 years old for women and 65.6 years old for men. The most frequent fracture risk factors were sedentary life (22.2 %) and previous fracture (15.8 %) in women and low calcium intake (21.4 %) and current smoker (20.9 %) in men. According to FRAX(®), the 10-year risk of presenting a major fracture was 5.5 % for the women and 2.8 % for the men. The 10-year risk for hip fracture was 1.9 and 1.1 % for the women and the men, respectively; 23.8 % of the women and 5.2 % of the men had a densitometry test, 27.7 % of the women and 3.5 % of the men were taking calcium and/or vitamin D supplements, and 28.2 % of the women (22.0 % in the 50-64 age group) and 2.3 % of the men were taking antiosteoporotic drugs. CONCLUSIONS: The prevalence of certain fracture risk factors not included in the FRAX tool (sedentary life, falls, low calcium intake) is high. In young women, their low risks estimated by FRAX contrast with the high figures for densitometry testing and treatment.

Development of a new predictive model for polypathological patients. The PROFUND index.

BACKGROUND: There is a concern about the accuracy of the available prognostic indexes when applying them to the emergent population of polypathological patients (PP). METHODS: To develop a 1-year mortality predictive index on PP, we developed a multicenter prospective cohort-study recruiting 1.632 PP after hospital discharge, outpatient clinics, or home hospitalization, from 33 hospitals. Potential risk factors were obtained in the 1.525 PP who completed follow-up. Each factor independently associated with mortality in the derivation cohort (757 PP from western hospitals) was assigned a weight, and risk scores were calculated by adding the points of each factor. Accuracy was assessed in the validation cohort (768 PP from eastern hospitals) by risk quartiles calibration, and discrimination power, by ROC curves. Finally, accuracy of the index was compared with that of the Charlson index. RESULTS: Mortality in the derivation/validation cohorts was 35%/39.5%, respectively. Nine independent mortality predictors were identified to create the index (age ≥85 years, 3 points; No caregiver or caregiver other than spouse, 2 points; active neoplasia, 6 points; dementia, 3 points; III-IV functional class on NYHA and/or MRC, 3 points; delirium during last hospital admission, 3 points; hemoglobinemia <10 g/dl, 3 points; Barthel index <60 points, 4 points; ≥4 hospital admissions in last 12 months, 3 points). Mortality in the derivation/validation cohorts was 12.1%/14.6% for patients with 0-2 points; 21.5%/31.5% for those with 3-6 points; 45%/50% for those with 7-10 points; and 68%/61.3% for those with ≥11 points, respectively. Calibration was good in derivation/validation cohorts, and discrimination power by area under the curve was 0.77/0.7. Calibration of the Charlson index was good, but discrimination power was suboptimal (area under the curve, 0.59). CONCLUSIONS: This prognostic index provides an accurate and transportable method of stratifying 1-year death risk in PP.

Solid-phase synthesis of graphitic carbon nanostructures from iron and cobalt gluconates and their utilization as electrocatalyst supports.

We present a novel and facile synthesis methodology for obtaining graphitic carbon structures from Fe(II) and Co(II) gluconates. The formation of graphitic carbon can be carried out in only one step by means of heat treatment of these organic salts at a temperature of 900 degrees C or 1000 degrees C under inert atmosphere. This process consists of the following steps: (a) pyrolysis of the organic gluconate and its transformation to amorphous carbon, (b) conversion of Fe(2+) and Co(2+) ions to Fe(2)O(3) and CoO and their subsequent reduction to metallic nanoparticles by the carbon and (c) conversion of a fraction of formed amorphous carbon to graphitic structures by Fe and Co nanoparticles that act as catalysts in the graphitization process. The removal of the amorphous carbon and metallic nanoparticles by means of oxidative treatment (KMnO(4) in an acid solution) allows graphitic carbon nanostructures (GCNs) to be selectively recovered. The GCNs thus obtained (i.e. nanocapsules and nanopipes) have a high crystallinity as evidenced by TEM/SAED, XRD and Raman analysis. In addition, we used these GCNs as supports for platinum nanoparticles, which were well dispersed (mean Pt size approximately 2.5-3.2 nm). Most electrocatalysts prepared in this way have a high electrocatalytical surface area, up to 90 m(2) g(-1) Pt, and exhibit high catalytic activities toward methanol electrooxidation.

Liver transplantation and hepatitis C virus. Results in a Spanish center since 1989.

BACKGROUND/AIMS: Hepatitis C-related liver disease is the main indication for liver transplantation in many centers. Viral RNA remains after transplantation in almost 100% of the patients, and more recent reports show a graft hepatitis rate of about 90%. The progression of this hepatitis seems to be quicker than in the nontransplant setting. METHODOLOGY: From June 1989 to October 2000, 197 adult patients had 213 for HCV-related liver disease at our institution. Basal immunosuppression consisted of a triple therapy with cyclosporine, azathioprine and steroids, or dual therapy with tacrolimus and steroids. None of the patients was treated with antivirals after liver transplantation. RESULTS: Pure HCV-related cirrhosis was the indication for liver transplantation in 114 patients, another 14 with hepatocellular carcinoma, 8 associated metabolic diseases, 43 high alcohol intake, 4 hepatitis B, 5 cholestatic diseases, and 3 other diseases. Six patients out of the 197 transplanted in this period were already grafted before this time, and had their first retransplantation of the liver after 1989 (their first liver transplantation was done when HCV was not known). Sixteen additional retransplantation procedures were done in the period considered. Hepatitis was diagnosed in 84.3% of the grafts biopsied later than 90 days after liver transplantation (118/140), and in 92.9% if it was done after one year (92/99). Cirrhosis was diagnosed in 21 grafts at a mean time of 1004.7 days, 21.2% of the grafts biopsied after 1 year and 28.6% after 2 years. Nine grafts in 8 patients were diagnosed as fibrosing cholestatic hepatitis. Patient actuarial survival was 80.9%, 69.7%, 67.5% and 50.6% at 1, 3, 5 and 10 years. Liver failure and hepatoma recurrence were the cause of death in 42.4% of the patients. Actuarial graft survival was 75.2%, 64.9%, 63.5% and 48.6% at 1, 3, 5 and 10 years, and was significantly affected by Child stage (B vs. C, P = 0.004). When compared to 228 non-HCV- infected patients with chronic parenchymatous disease, these had an almost significantly better patient survival (P = 0.0577), but a nonsignificant difference in graft survival. Graft loss related to liver causes was 17.6% in HCV+ patients 14.6% in HCV- patients. Liver causes of death were 14.0% in HCV+ patients and 4.8% in HCV-patients (P = 0.002). CONCLUSIONS: HCV infected liver transplantation recipients present very often graft hepatitis, which may progress to advanced stages in a quite short interval. Mid-term patient and graft survival is comparable to those of non-HCV recipients, but causes of death related directly to liver disease are more common in HCV+. This makes one think that long-term prognosis (more than 10 or 15 years) will be worse in HCV patients.

Function search in a large transcription factor gene family in Arabidopsis: assessing the potential of reverse genetics to identify insertional mutations in R2R3 MYB genes.

More than 92 genes encoding MYB transcription factors of the R2R3 class have been described in Arabidopsis. The functions of a few members of this large gene family have been described, indicating important roles for R2R3 MYB transcription factors in the regulation of secondary metabolism, cell shape, and disease resistance, and in responses to growth regulators and stresses. For the majority of the genes in this family, however, little functional information is available. As the first step to characterizing these genes functionally, the sequences of >90 family members, and the map positions and expression profiles of >60 members, have been determined previously. An important second step in the functional analysis of the MYB family, through a process of reverse genetics that entails the isolation of insertion mutants, is described here. For this purpose, a variety of gene disruption resources has been used, including T-DNA-insertion populations and three distinct populations that harbor transposon insertions. We report the isolation of 47 insertions into 36 distinct MYB genes by screening a total of 73 genes. These defined insertion lines will provide the foundation for subsequent detailed functional analyses for the assignment of specific functions to individual members of the R2R3 MYB gene family.

Fibrosing cholestatic hepatitis in hepatitis C virus-infected renal transplant recipients.

Severe hepatitis C virus (HCV)-related fibrosing cholestatic hepatitis leading to early liver failure has been reported only exceptionally. Of 259 HCV-infected renal transplant (RT) patients in one hospital unit, four (1.5%) are described, representing the first series of this particular post-RT disease. Patient mean age was 55.7 yr. Three were men. All had pretransplant, hepatitis B surface antigen-negative and were anti-HCV antibodies positive. Three of them showed pretransplant mild liver enzyme abnormalities, and all received kidneys from HCV-negative donors. All were on steroids, cyclosporine, and azathioprine (AZA). The clinical pattern appeared early after RT (mean, 11.5 mo). In three patients, hyperbilirubinemia (6.5 to 20 mg/dl) and high alkaline phosphatase levels (428 to 859 IU/L) were observed. Also, in all subjects, high gamma glutamyl transpeptidase levels (639 to 4270 IU/L), mild aspartate aminotransferase and alanine aminotransferase abnormalities, and serum HCV RNA were observed. Liver biopsy revealed diffuse fibrosis, leukocyte infiltrates, and different degrees of cholestasis, with typical signs of HCV hepatitis in only one patient. Two patients developed subfulminant liver failure and died 2 and 3 mo after biopsy, respectively. One patient also suffered hepatic failure, receiving a liver transplant. The fourth is alive on dialysis awaiting a combined kidney and liver transplant. It is concluded that fibrosing cholestatic hepatitis is a new, early, and severe complication after RT in HCV(+) patients, which appears in patients with ongoing HCV infection under AZA therapy, despite a nonaggressive immunosuppressive protocol. Both HCV and AZA could play a concurrent role in the pathogenesis of this severe complication after RT.

Membranous glomerulonephritis associated with hepatitis C virus infection in renal transplant patients.

BACKGROUND: Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. METHODS: From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). RESULTS: Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (<2 g/24 h.). CONCLUSIONS: In summary, HCV is preferentially associated with MGN in renal transplant patients, rather than with membranoproliferative glomerulonephritis as in the normal adult population. MGN associated with HCV infection has a similar clinical picture and outcome to posttransplant idiopathic de novo MGN, with persistent massive proteinuria and progressive deterioration of renal function.

Influence of viral genotype and level of viremia on the severity of liver injury and the response to interferon therapy in Spanish patients with chronic C infection.

BACKGROUND: We wanted to investigate the influence of viral genotype on the severity of liver injury and response to interferon and whether the level of viremia differs in accordance with genotype, severity of liver disease, and response to interferon in patients with hepatitis C virus (HCV) infection. METHODS: We studied 118 patients with HCV-related liver disease. HCV genotypes were determined with a line probe assay, and serum HCV RNA levels with a competitive reverse transcription polymerase chain reaction assay. RESULTS: HCV type 1b was the most prevalent genotype (88%). It was present in 100% of cirrhotic patients, with or without hepatocellular carcinoma (HCC), but only in 78% of patients with chronic hepatitis (P < 0.001). The response to interferon was better in patients infected with non-1b HCV genotypes (P = 0.002). In a multivariate analysis non-1b HCV genotypes and a low hepatic fibrosis correlated with a favorable response to interferon. Among patients with chronic hepatitis those infected with HCV type 1b were older (P < 0.001), and age was the only independent factor associated with HCV type 1b. Viremia levels differed neither between genotypes nor in response to interferon and was significantly lower in patients with cirrhosis and HCC. CONCLUSIONS: HCV 1b was associated with more severe liver disease and a worse response to interferon therapy. Non-1b genotypes and a lower liver fibrosis were the only independent predictors of a favorable response to interferon. Levels of HCV viremia differed neither among different genotypes nor in response to interferon and decreased with advanced liver disease.

A single residue substitution causes a switch from the dual DNA binding specificity of plant transcription factor MYB.Ph3 to the animal c-MYB specificity.

Transcription factor MYB.Ph3 from Petunia binds to two types of sequences, MBSI and MBSII, whereas murine c-MYB only binds to MBSI, and Am305 from Antirrhinum only binds to MBSII. DNA binding studies with hybrids of these proteins pointed to the N-terminal repeat (R2) as the most involved in determining binding to MBSI and/or MBSII, although some influence of the C-terminal repeat (R3) was also evident. Furthermore, a single residue substitution (Leu71 --> Glu) in MYB.Ph3 changed its specificity to that of c-MYB, and c-MYB with the reciprocal substitution (Glu132 --> Leu) essentially gained the MYB.Ph3 specificity. Molecular modeling and DNA binding studies with site-specific MYB.Ph3 mutants strongly supported the notion that the drastic changes in DNA binding specificity caused by the Leu --> Glu substitution reflect the fact that certain residues influence this property both directly, through base contacts, and indirectly, through interactions with other base-contacting residues, and that a single residue may establish alternative base contacts in different targets. Additionally, differential effects of mutations at non-base-contacting residues in MYB.Ph3 and c-MYB were observed, reflecting the importance of protein context on DNA binding properties of MYB proteins.

[A comparative randomized controlled study of the efficacy of interferon alfa-2b and interferon alfa-2a in the treatment of chronic hepatitis C]. / Estudio comparativo, aleatorizado y controlado de la eficacia del interferón alfa-2b e interferón alfa-2a en el tratamiento de la hepatitis crónica C.

Interferon (INF) is the treatment of choice in active chronic hepatitis C although the optimum therapeutic schedule remains undefined to date. One forty-eight patients with active chronic hepatitis C were included in a randomized controlled study to compare the therapeutic efficacy of 2 types of recombinant alpha IFN: alpha-2b IFN and alpha-2a IFN. Twelve patients were excluded from the study for different reasons. The groups were made up of 34 untreated patients (group I), 68 patients treated with 5 MU of alpha-2b IFN three times per week for 12 months (group II) and 32 patients with 6 MU of alpha-2a IFN three times per week for one year (group III). On finalization of the treatment 39 patients from group II (57%) and 20 (63%) from group III showed normal transaminases (p > 0.05) while this was not so in any patient from group I (p < 0.001). HCV infection of less than 5 years was significantly associated with complete biochemical response. During the post treatment follow up (16.2 +/- 11.1 months; range: 6-45 months) the transaminase levels reelevated in 26 (67%) responding patients from group II and in 12 (60%) patients from group III (p > 0.05). Therefore complete biochemical response was maintained in only 12 (19%) of the patients from group II and in 8 (25%) of the patients from group III (p > 0.05). Liver biopsy was carried out in the 3 post treatment months in 15 patients from group I, 29 from group II and 18 patients from group III with all the rebiopsied patients from groups II and III having demonstrated complete or partial response to IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Laminin fragment P1 is increased in the lower respiratory tract of patients with diffuse interstitial lung diseases.

Laminin is a 900,000-dalton extracellular matrix glycoprotein involved in a variety of functions, including cellular movement, growth, and differentiation. The aim of this work was to investigate the presence and biologic significance of this substance in the bronchoalveolar lavage fluid (BALF) of diffuse interstitial lung diseases (DILD). Levels of laminin fragment P1 (LFP) were measured by radioimmunoassay in BALF and sera from controls (n = 8) and patients with several types of DILD: sarcoidosis (n = 10), neoplastic pulmonary infiltration (n = 8), pulmonary fibrosis (n = 5), and hypersensitivity pneumonitis (n = 5). Furthermore, their relation to signs of alveolitis (cellular profiles and albumin concentration in BALF) and evidence of pulmonary fibroblast activation (BALF aminoterminal propeptide of type III procollagen) was examined. Laminin fragment P1 immunoreactivity was detectable in BALF, even in the control group, but patients with all types of DILD had higher concentrations than the control subjects. The serum levels of LFP were similar in all groups studied. Neutrophil and lymphocyte proportions were significantly higher in all DILD groups than in the control group. A positive correlation was seen between lymphocyte proportion and laminin fragment P1 in BALF. Moreover, in BALF a positive correlation was found between LFP and albumin and between LFP and the aminoterminal propeptide of type III procollagen. The BALF macrophage-associated laminin fragment P1 was significantly higher in the active sarcoidosis subgroup compared with the control group. Thus, laminin is a normal constituent of the epithelial lining fluid. The increase of laminin in BALF of patients with DILD suggests that laminin may contribute to their pathogenesis.