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Background: In COPD, the bronchial epithelium shows a pathologically activated Wnt pathway. Sclerostin (SOST) is a secreted glycoprotein that is associated with bone metabolism and blocks the Wnt pathway. We hypothesized that low sclerostin levels might be associated with lung function and COPD exacerbations in patients., Methods: We studied 139 outpatients with stable COPD and normal kidney function. We assessed the serum levels of SOST and bone metabolism parameters, body composition, clinical characteristics and lung function at baseline. We followed the patients prospectively for 12 months after enrolment. Moderate exacerbations and hospital admissions were recorded during follow-up., Results: The serum SOST levels were 23.98±7.6 pmol/l (men: 25.5±7.7 pmol/l, women: 20.3±5.9 pmol/l (p < 0.001)). SOST showed correlations with age (r = 0.36), FFMI (r = 0.38), FEV1 (r = 0.27), DLCO (r = 0.39), 6MWD (r = 0.19) and CAT (r = -0.24). In multivariate linear regression analysis, only age (beta=0.264) and FFMI (beta=1.241) remained significant. SOST showed a significant negative correlation with serum phosphorus (r = -0.29). Cox proportional risk analysis indicated that patients in the lower tertile of SOST levels were at higher risk of moderate COPD exacerbation (HR 2.015, CI95% 1.136-3.577, p = 0.017) and hospital admission due to COPD (HR 5.142, CI95% 1.380-19.158, p = 0.015) than the rest of the patients., Conclusions: SOST levels are associated with body composition and lung function in patients with COPD. Furthermore, lower SOST levels predict a higher risk of exacerbations and hospitalization., Competing Interests: Declaration of interests None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

GES (Guiana Extended Spectrum) carbapenemases belong to "minor class A carbapenemases" and its prevalence could be underestimated due to the lack of specific tests. The aim of this study was to develop an easy PCR method to differentiate between GES β-lactamases with or without carbapenemase activity, based on an allelic discrimination system of SNPs that encode E104K and G170S mutations, without need of sequencing. Two pair of primers and Affinity Plus probes, labeled with different fluorophores; FAM/IBFQ and YAK/IBFQ, were designed for each one of the SNPs. This allelic discrimination assay allows to detect in real time the presence of all type of GES- β-lactamases, being able to differentiate between carbapenemases and extended-spectrum β-lactamase (ESBL), through a quick PCR test that avoid costly sequencing approaches and could help to decrease the current underdiagnosis of minor carbapenemases that scape of phenotypic screenings., Competing Interests: Declaration of Competing Interest The authors have no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Co-circulation of the two Influenza B lineages hinders forecast of strain to include in trivalent vaccine. Autonomous Communities such as Cantabria continue without supplying tetravalent vaccine. The aim of this study was to analyse epidemiological characteristics of influenza type B in Cantabria (2019-2020 season) as well as to establish the predominant lineage and its relation to the recommended vaccine., Methods: Retrospective study whereby flu diagnosis and lineage analysis were determined by RT-PCR., Results: All samples belonged to the Victoria lineage. Most prevalent viral co-infection was due to SARS-CoV-2. The population affected by influenza B was mainly paediatric and non-vaccinated patients more frequently required hospital admittance., Conclusions: Influenza type B has a higher incidence in the paediatric population and type A affects more the adult population. Only 28.8% of patients with Influenza B that presented with some underlying condition or risk factor were vaccinated. This shows the need to increase coverage with tetravalent vaccines in order to reduce the burden of disease associated with the Influenza B virus., (©The Author 2020. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Leishmaniasis is a zoonotic disease caused by intracellular protozoa of the Leishmania genus that are spread and transmitted by sandflies. Natural infection and clinical disease in domestic cats and dogs appear to be rare or perhaps largely under-reported in endemic areas. However, previous reports on infected domestic animals usually implicate the same Leishmania species that affect humans in tropical and subtropical areas of the world suggesting a potential role for zoonotic transmission. In the present study we assessed a representative sample of cats and dogs from endemic urban / suburban areas of Lara state in central western Venezuela. In both dogs and cats, cutaneous disease exhibits a spectrum of manifestations that range from single papules or nodules, which may evolve into ulcerative, plaque-like or scaly lesions. Cytochrome b (cyt b) PCR gene sequence analysis revealed L. mexicana as the causative agent in all cases, including two human cases proceeding from the same study area at the same time the study was carried out. In order to improve our understanding on feline/canine infection with Leishmania mexicana, and address potential zoonotic concerns it is necessary to characterize its enzootic reservoirs and vectors as well as the possible anthropophilic players linking to the peridomestic and domestic cycles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Spontaneous bacterial peritonitis (SBP) is a frequent and severe entity in patients with cirrhosis or ascites due to other causes. However, Listeria monocytogenes is a microorganism that has been scarcely identified as a causative agent of SBP., Methods: In this study, a descriptive analysis of cases of L. monocytogenes SBP was carried out in our center for 26 years (1992-2017)., Results: A total of eight patients were diagnosed, with an average age of 58 years, with no differences in sex distribution and all of them were community acquired cases. Half of the patients had underlying liver disease, two of them active malignancies; one was undergoing continuous ambulatory peritoneal dialysis and the last one with hypertensive heart disease. Six (75%) of the patients received a third-generation cephalosporin as empirical treatment. The clinical course was favorable after receiving directed antibiotic treatment in five (62.5%) of the patients. However, three of them, under the age of 59, died. Serotyping of L. monocytogenes isolates revealed that half of them were serovar 4, two 1 / 2a and the remaining one 1 / 2c. All strains were susceptible to ampicillin, meropenem, erythromycin and cotrimoxazole., Conclusions: We conclude by emphasizing the importance of taking this etiology into account in patients with underlying liver disease and with clinical or laboratory data suggesting SBP, mainly due to the need for specific antibiotic treatment different from conventionally empirically used., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

The aims of this study were to determine the correlation of mutations in the ftsI gene (coding for PBP3) of Haemophilus influenzae with aminopenicillin resistance and to evaluate the 2017 European Committee for Antibiotic Susceptibility Testing (EUCAST) guidelines for clinical categorization of ampicillin, amoxicillin, and amoxicillin-clavulanate for strains with mutated PBP3 conferring resistance (rPBP3). A panel of 91 H. influenzae isolates was genetically characterized by sequencing of the fstI gene. For all the studied isolates, a screening with benzylpenicillin 1U (BP1) was carried out and minimum inhibitory concentrations (MICs) of ampicillin, amoxicillin, and amoxicillin-clavulanate were tested and interpreted according to EUCAST recommendations. ftsI sequence analysis revealed a total of 14 different amino acid substitutions in PBP3. The substitution patterns most commonly observed were [D350N, M377I, A502V, N526K] among the bla-positive rPBP3 strains (37.5%) and [D350N, A502T, N526K] among the bla-negative rPBP3 strains (24.5%). Screening with BP1 was able to correctly categorize 100% of the bla-negative sPBP3 strains, 100% of the bla-positive strains, and 92% of the bla-negative rPBP3 ones. Only 29% of the bla-negative rPBP3 strains evaluated displayed ampicillin MICs above the current EUCAST resistant breakpoint defined at 1 μg/ml. The PBP3 substitution patterns of the strains evaluated are similar to the ones observed in previous Spanish and European studies. Although the screening with BP1 proved to be adequate in the detection of bla-negative rPBP3 strains, these cannot be reliably identified by current 2018 EUCAST breakpoints for ampicillin.

Objective: Rapid identification of pathogens is essential for the diagnosis of gastrointestinal infections. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry has shown to be effective and fast for the identification of microorganisms. The objective of this study was to evaluate the correlation between Vitek-MSTM and conventional methods for bacterial identification causing gastrointestinal infection., Methods: A total of 329 gastrointestinal pathogens were identified using Vitek-MSTM (v2 SARAMIS MS -ID, bioMérieux, Marcy-I´Étoile, France) and routine diagnostic methods simultaneously. In cases of discrepancy 16SrRNA gene sequencing was performed., Results: The correlation between Vitek-MSTM and diagnostic methods was 100% except for Yersinia enterocolitica (94.1%), Helicobacter pylori (10%) and Aeromonas veronii (0 %)., Conclusions: Vitek-MSTM is a quick and useful method for identification of enterophatogenic bacteria. It is necessary to improve the performance of the system for the identification of H. pylori and A. veronii.

Background: WU and KI polyomaviruses were discovered in 2007 in samples of respiratory secretions of children with acute respiratory symptoms. Seroepidemiologic studies have shown that these viruses are widely distributed throughout the world, but their incidence in Spain has not been determined. In transplant patients, early detection and treatment of viral infections may influence prognosis and survival, because they are associated with increased morbidity and mortality, including graft failure., Methods: We aimed to determine the prevalence and clinical characteristics of WU and KI polyomaviruses among patients undergoing hematologic or solid organ transplant in the Hospital Marqués de Valdecilla (Santander, Spain). An in-house polymerase chain reaction with the use of specific primers was carried out in invasive lower respiratory samples from hospitalized patients with suspected respiratory infection and/or graft dysfunction and compared with asymptomatic transplant patients., Results: Overall, we obtained 5.5% KI-positive samples and 1.4% WU-positive samples, with a higher prevalence of WU and KI polyomaviruses in the symptomatic population compared with the control group. Although the data suggest that their detection in respiratory samples is sporadic and often associated with other microorganisms, we should pay special attention to their association with cases of graft failure. Studies are needed with a larger number of samples to explore the potential clinical impact of these emerging polyomaviruses in transplant recipients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Describe a school outbreak of tuberculosis and compare the features with other outbreaks. Propose mediastinal ultrasound as an aid in its diagnosis and monitoring., Patients and Methods: Retrospective descriptive study of the transmission of tuberculosis infection in a micro-epidemic. Infection criteria: Mantoux ≥ 5mm, asymptomatic patient, with normal radiological, microbiological and analytical studies. Disease criteria: Mantoux ≥ 5mm and any of the above pathological studies. Mediastinal ultrasound was used as a complementary method of chest radiography (CXR). Computed tomography (CT) as the combined result of ultrasound and CXR was inconclusive., Results: Seventeen out of 412 students were infected and 16 with tuberculosis disease. In addition, 4 out-school contacts were diagnosed of tuberculosis., Clinical Manifestations: one erythema nodosum, one Henoch-Schönlein purpura, twelve with cough and fever nine. CXR results in patients: 3 normal, 7 inconclusive, and 10 with the following findings: 2 pneumonia, 2 pulmonary atelectasis, 2 primary complexes, 4 patients only with lymphadenopathy. All patients with normal or indeterminate CXR showed mediastinal lymphadenopathy visualized on ultrasound but 3 demonstrated by CT. Microbiological isolation: 6 cases (31%)., Conclusions: The number of infected patients was higher compared to other outbreaks There is great variability in the diagnostic approach to tuberculosis micro-epidemics. It is complex to differentiate between infection and disease. The clinical, laboratory and CXR are nonspecific. There are patients with normal CXR, pathological ultrasound and microbiological isolation. Mediastinal ultrasound can play an important role in the diagnosis and management of tuberculosis disease., (Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

The purpose of this investigation was to determine the prevalence of plasmid-mediated AmpC (pAmpC) and carbapenemases in Enterobacteriaceae collected from 35 hospitals in Spain and to establish their epidemiological relationships. We conducted a prospective multi-centre study on pAmpC- or carbapenemase-producing Enterobacteriaceae isolates from clinical samples collected from February to July 2009. The strains suspected to carry pAmpC were resistant or showed intermediate susceptibility to co-amoxiclav and second- or third-generation cephalosporins. Strains suspected to carry a carbapenemase were selected because they showed a minimum inhibitory concentration (MIC) to imipenem >1 mg/L. Polymerase chain reaction (PCR) and a sequencing strategy were used to characterise the enzymes. The clonal relationships between isolates was analysed by pulsed field gel electrophoresis (PFGE). Among 100,132 Enterobacteriaceae isolates collected, 1,654 were compatible with the production of pAmpC or carbapenemases. We found a prevalence of 0.64 % of pAmpC (n = 635) and 0.04 % of carbapenemases (n = 43). The most prevalent pAmpC enzymes were CMY-type (78.3 %), DHA-type (19.5 %), ACC-type (1.6 %) and FOX-type (0.6 %). The CMY-type was the most frequent in Escherichia coli and Proteus mirabilis species, whereas the DHA-type was mainly found in Klebsiella spp. The enzymes involved in carbapenem resistance were VIM-1, IMP-22 and the new IMP-28. Nine new bla genes were described: bla (CMY-54), bla (CMY-55), bla (CMY-56), bla (CMY-57), bla (CMY-96), bla (DHA-6), bla (DHA-7), bla (FOX-8) and bla (IMP-28). The prevalence of pAmpC or carbapenemases found is not negligible. The CMY-types were the predominant pAmpC, whereas the VIM or IMP enzymes were the predominant carbapenemases. Furthermore, we observed a great genetic diversity among pAmpC-producing strains and a close clonal relationship between carbapenemase-producing strains.

The goal of heart transplantation (HT) is not only to prolong the life of patients with end-stage heart failure, but also to offer them the sort of health they enjoyed before the disease. It is widely known that patients' functional capacity improves after HT but what about their quality of life (QoL)? Do functional capacity and QoL improve simultaneously? In the present study, we compared the progression of effort capacity and QoL in the first 2 years after HT. A prospective longitudinal study was performed in 58 heart transplant recipients (43 males, 15 females, age 51.6 ± 10 years) able to complete an effort test 2, 6, 12, and 24 months after transplantation. The studied variables included the five dimensions of the Euroqol-5D questionnaire (EQ-5D) test: mobility, self-care, daily activities, pain/discomfort, anxiety, and depression; a visual analog scale from 0 to 100; and the results (metabolic equivalent units [METs] and time of exercise) of the effort test at 2, 6, 12, and 24 months after transplantation. Analysis of variance was used to compare these variables at each point. Significance was set at P < .05. Functional capacity, measured by both METs and time of exercise, improved progressively (METs: 2 months: 5.2 ± 1.8, 6 months: 6.6 ± 2.1, 12 months: 7.5 ± 2.2, and 24 months: 8.5 ± 2.3, P < .001). As well, the result of EQ-5D questionare improved in parallel to exercise capacity. However, visual analog scale score did not change significatively during the follow-up (2 months: 78.9.3 ± 16.1, 6 months: 83.8 ± 11.3, 12 months: 83.3 ± 11.1, 24 months: 85.2 ± 14.9; P = .192), reaching a plateau at 6 to 24 months. In conclusion, the improvement in functional capacity shown by heart transplant recipients in the first 2 years after transplantation was not parallel to the feelings of well-being measured by the analog scale of the EQ-5D. Possibly long after transplantation patients will compare themselves to healthy people rather than to their state before HT, resulting in improvements the visual analog scale., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon-gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB-gold In Tube (QFT-GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD)., Patients and Methods: Fifty-four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT-GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x-rays. Agreement between test results was determined., Results: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT-GIT and TST was fair (k=0.36; P=.006), as it was between TST and expert physician's evaluation (k=0.257; P=.06)., Conclusions: According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST.

Introduction and Aims: Tumors are the second leading cause of death beyond the first year heart transplantation (HT). The aim of our study was to establish a chronology for the occurrence and the impact on overall survival of de novo neoplasms after HT., Materials and Methods: We included 597 patients undergoing HT from January 1987 to December 2008. De novo tumors were classified into groups: Kaposi's sarcoma, melanoma, epidermoid skin carcinoma, other skin tumors, lung neoplasms, bladder tumors, prostate adenocarcinoma, digestive tumors, lymphomas, and other tumors. We based the study on the median value and interquartile range of the tumors to estimate their occurrence. Survival rates were calculated using Kaplan-Meier curves and the log-rank tests. We included only patients with survivals beyond 1 year after HT., Results: A total of 109 tumors developed during the follow-up. There were no differences in the survival of patients who lived more than 1 year regarding the development or not of a tumor (155±8 vs 179±6 months; P=.177)., Conclusions: The incidence of tumor occurrence after HT was high (18.25%). There were several periods in which the occurrence of certain tumors was more frequent, while other periods appeared to be tumor-free. As most tumors were skin cancers, their impact on overall survival was low., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Heart transplant recipients show an abnormal heart rate (HR) response to exercise due to complete cardiac denervation after surgery. They present elevated resting HR, minimal increase in HR during exercise, with maximal HR reached during the recovery period. The objective of this study was to study the frequency of normalization of the abnormal HR in the first 6 months after transplantation., Materials and Methods: We prospectively studied 27 heart transplant recipients who underwent treadmill exercise tests at 2 and 6 months after heart transplantation (HT). HR responses to exercise were classified as normal or abnormal, depending on achieving all of the following criteria: (1) increased HR for each minute of exercise, (2) highest HR at the peak exercise intensity, and (3) decreased HR for each minute of the recovery period. The HR response at 2 months was compared with the results at 6 months post-HT., Results: At 2 months post-HT, 96.3% of the patients showed abnormal HR responses to exercise. Four months later, 11 patients (40.7%) had normalized HR responses (P<.001), which also involved a significant decrease in the time to achieve the highest HR after exercise (124.4±63.8 seconds in the first test and 55.6±44.6 seconds in the second). A significant improvement in exercise capacity and chronotropic competence was also shown in tests performed at 6 months after surgery., Conclusions: We observed important improvements in HR responses to exercise at 6 months after HT, which may represent early functional cardiac reinnervation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction and Aims: The shortage of donor organs has prompted increased acceptance of hearts from donors with more comorbidities. With increasing frequency, hearts are being offered from patients who have undergone a resuscitated cardiac arrest (RCA). Our aim was to compare the rate of complications in the postoperative and follow-up periods, depending on whether the transplanted organ came from a donor who had undergone an RCA., Materials and Methods: We included all 604 heart transplantations (HTs) performed in our center from 1987 to 2009, including 25 recipients who received an organ from a donor who had undergone RCA. We considered RCA to be an in-hospital cardiac arrest that was resuscitated from the onset, with a duration of <30 minutes, and with total recovery of cardiac and hemodynamic function. We analyzed ischemia time, incidence of acute graft failure (AGF), intubation period, recovery room stay, and long-term survival. The statistical methods were Student t and chi-square tests., Results: There were no differences in baseline characteristics, except that patients in the RCA group were younger (47±13 vs 51±11 years; P=.50). There were also no differences between the RCA group and the other patients in ischemia time (151±50 vs 154±53 minutes; P=.826), incidence of AGF (33% vs 24.7%; P=.311), hours of intubation (76±204 vs 72±249; P=.926), days of recovery room stay (6±7 vs 8±6; P=.453), or survival after HT (53±54 vs 53±52 months; P=.982)., Conclusions: Patients receiving a heart from a patient with an in-hospital RCA and subsequent hemodynamic stability have a similar outcomes to other HT patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction and Aim: After cardiac allograft vasculopathy, tumors are the second leading cause of death among heart transplantation (HT) patients after the first year. Lymphomas are tumors of lymphocytic origin whose development has been associated with the use of anti-CD3 monoclonal antibody (OKT3). Some studies suggest that the use of acyclovir could counteract this effect. Our aim was to investigate the impact of gancyclovir on OKT3 and lymphoma development after HT., Materials and Methods: We included all 239 HTs performed in our center from 1989 to 2002. We divided patients into those who received gancyclovir treatment (prophylaxis, pre-emptive therapy, or for cytomegalovirus infection) versus those who did not receive this agent at any time during follow-up (88 vs 151 patients). The statistical methods were Student's t and chi-square tests., Results: There were no differences in the baseline characteristics of the patients--gender, recipient age, etiology leading to HT, diabetes, and dyslipidemia--except for a higher rate of hypertension among the group who did not receive gancyclovir (73.7 vs 60.2%; P=.03). None of the 7 patients who developed lymphomas during the follow-up received gancyclovir (0 vs 4.6%; P=.040)., Conclusions: Antivirals may have a relevant role to neutralize potential neoplastic effects (especially lymphomas) associated with the use of OKT3 induction therapy., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background and Aim: The drugs routinely administered to prevent rejection often cause lethal side effects. Tolerant patients, therefore, should be identified to minimize these problems. The aim of this analysis was to identify clinical variables that may be associated with tolerance., Methods: We recruited 522 heart transplants (HT), excluding combined procedures, retransplantations, pediatric recipients, and subjects who died in the first year to obtain a cohort of 375 patients. Two groups were distinguished by the presence of echocardiographic, clinical, or pathological evidence of rejection in the first year (15 echocardiograms and 10 protocol biopsies per patient); 99 tolerant patients were compared with 276 nontolerant patients. We analyzed clinical variables related to morbidity and mortality., Results: The univariate analysis showed few differences between the groups. The multivariate analysis showed that only major histocompatibility complex (MHC)-A and MHC-DR matched recipients were significantly associated with tolerance. Thus, the likelihood of tolerance was increased by 1.7- and 2.8-fold if 1 or 2 MHC-I matches were present and by 3.4- and 3.7-fold if 1 or 2 MHC-DR matches were present, respectively survival curves showed significant differences (P=.034). Most deaths in both groups were related to immunosuppressive drugs; among tolerant subjects, deaths were due to infection and neoplasms and among nontolerant patients, deaths were due to chronic rejection, neoplasms, and infection., Conclusions: The only clinical parameter that can determined whether a HT recipient was tolerant was MHC-A and MHC-DR matching. If there is matching, a reduced immunosuppressive load should be prescribed to prevent drug toxicity., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction and Aims: Cardiac allograft vasculopathy (CAV) is the leading cause of death after the first year post-heart transplantation (HT). Numerous factors have been implicated in the development of CAV. The aim of this prospective randomized study was to assess the impact of cyclosporine (CsA) and tacrolimus (Tac) on the development of CAV., Materials and Methods: From November 2006 to October 2008, 49 HT patients in our center were randomized to receive CsA or Tac. The additional treatment for all patients consisted of daclizumab induction and maintenance treatment with mycophenolate mofetil (1 g/12 hours) and steroids (withdrawal was not attempted). Thirteen patients died before coronary arteriography plus intravascular ultrasound of the left anterior descending artery was performed at 1 year after HT. Hence, the final number of patients included was 36 (18 per group). We considered significant CAV to be the presence of intimal proliferation>1 mm and/or>0.5 mm in 180°. The statistical methods were Student t and chi-square tests., Results: There were no differences in baseline characteristics between the two groups. Nor were there significant differences in maximum intimal proliferation between the groups (CsA 0.65±0.29 vs Tac 0.82±0.51 mm; P=.292) or in the development of significant CAV when both criteria were combined (CsA 31.6% vs Tac 38.9%; P=.642)., Conclusions: One year after HT, no differences were detected in the development of significant CAV according to the type of calcineurin inhibitor used when combined with daclizumab induction and maintenance treatment with mycophenolate mofetil and steroids., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers., Objective: To analyze the utility of various inflammatory markers, which is most important and what values best classify patients to diagnose rejection., Materials and Methods: A prospective study in 123 consecutive cardiac transplant recipients was conducted from January 2002 to December 2006. Fibrinogen protein (Fgp) and function (Fgf), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and sialic acid (SA) determinations were performed at one, two, four, six, nine, and 12 months post-HT at the same time as biopsies. Coronary arteriography and intravascular ultrasound were performed on the first and last follow-up visits. Heart-lung transplants, retransplants, pediatric transplants, patients who died in the first month, and patients who refused consent were excluded. Also excluded were determinations that coincided with renal dysfunction, active infection, hemodynamic instability, or a non-evaluable biopsy. The final analysis included 79 patients and 294 determinations. The correlation between the levels of these biomarkers and the presence of rejection in the biopsy (> or = ISHLT grade 3) was studied., Results: We did not find significant differences in the values of any of the markers analyzed on the six follow-up visits. Only CRP showed significant and sustained differences between the two groups (with and without rejection) from the second follow-up visit (month 2). The area under the curve showed significant differences in Fgp (0.614, p = 0.013), Fgf (0.585, p = 0.05), TNF-alpha (0.605, p = 0.02), SA (0.637, p = 0.002) and mainly CRP (0.765, p = 0.0001). CRP levels below 0.87 mg/dL ruled out rejection with a specificity of 90%., Conclusions: Among the inflammatory markers analyzed, CRP was the most useful parameter for non-invasive screening of acute cellular rejection in the first year post-HT.

We have studied by PCR and DNA sequencing the presence of the qnrA, qnrB, qnrS, aac(6')-Ib-cr, qepA, intI1, and ISCR1 genes in 200 clinical isolates of Enterobacter cloacae (n = 153) and E. aerogenes (n = 47) consecutively collected between January 2004 and October 2005 in two hospitals located in Santander (northern Spain) and Seville (southern Spain). Mutations in the quinolone resistance-determining region of gyrA and parC also were investigated in organisms containing plasmid-mediated quinolone resistance genes. The isolates had different resistant phenotypes, including AmpC hyperproduction, extended-spectrum beta-lactamase production, resistance or decreased susceptibility to quinolones, and/or resistance to aminoglycosides. Among the 116 E. cloacae isolates from Santander, qnrS1, qnrB5, qnrB2, and aac(6')-Ib-cr were detected in 22 (19%), 1 (0.9%), 1 (0.9%), and 3 (2.6%) isolates, respectively. Twenty-one, 17, and 2 qnrS1-positive isolates also contained bla(LAP-1), intI1, and ISCR1, respectively. A qnrB7-like gene was detected in one E. aerogenes isolate from Santander. No plasmid-mediated quinolone resistance gene was detected in the isolates from Seville. The qnrS1-containing isolates corresponded to four pulsed-field gel electrophoresis patterns and showed various levels of resistance to quinolones. Six isolates were susceptible to nalidixic acid and presented reduced susceptibility to ciprofloxacin. The qnrS1 gene was contained in a conjugative plasmid of ca. 110 kb, and when the plasmid was transferred to recipient strains that did not have a specific mechanism of quinolone resistance, the ciprofloxacin MICs ranged from 0.047 to 0.125 microg/ml.

Objective: Exercise capacity has been shown to be reduced among cardiac transplant recipients. This observation is directly connected to both the transplanted heart's dependence on circulating catecholamines and the abnormal sympathoadrenal response to exercise in these patients. Taking into account this background, there is reluctance to use beta-blockers after heart transplantation. Nevertheless, this point remains controversial. Our aim was to examine exercise tolerance after an oral dose of atenolol early after cardiac transplantation., Materials and Methods: Eighteen nonrejecting, otherwise health, cardiac transplant recipients were included in this study at a mean of 61.9 +/- 25.6 days after surgery; 13 were men. Patients performed controlled exercise to a symptom-limited maximum before and 2 hours after taking an oral dose of atenolol. Heart rate, blood pressure, exercise time, and metabolic equivalent units (METS) were recorded at rest as well as during and after exercise. We compared results depending on taking atenolol., Results: Resting (101.7 +/- 14.5 vs 84 +/- 12.4 bpm; P = .001) and peak heart rates (128.5 +/- 12.9 vs 100.7 +/- 16 bpm; P = .001) were significantly higher before than after beta blockade. Resting systolic blood pressure was slightly higher before compared with after beta blockade (129.3 +/- 23.6 vs 122.2 +/- 20.3 mm Hg; P = .103). However, there was neither a significant difference in the length of exercise (3.17 +/- 1.96 vs 3.40 +/- 2.48 minutes; P = .918) nor in the estimated oxygen consumption (METS; 5.07 +/- 1.8 vs 5.31 +/- 2.2; P = .229). Furthermore, no patient reported a greater degree of tiredness after beta blockade., Conclusions: This study showed little adverse effect on exercise tolerance by beta blockade in recently transplanted patients. Atenolol seemed to be safe in this context.

Mycobacterium xenopi is an unusual pathogen and few such cases have been reported in the literature. We report the case of a patient with a sirolimus-based immunosuppressive regimen, who developed lung cavitation. M. xenopi was isolated from the sputum. The patient was treated initially with rifampicin, isoniazid, and pyrazinamide; levofloxacin was added to the treatment regimen after M. xenopi was demonstrated. A possible relationship between sirolimus and M. xenopi infection has been postulated, probably due to the combination of pulmonary toxicity and cellular immunosuppression of rapamycin.

Introduction and Objectives: The immediate postoperative period is a critical phase in heart transplantation. Severe complications occur that may influence short-term and medium-term morbidity and mortality in these patients. The aim of this study was to analyze the incidence of severe complications in emergency and nonemergency transplantations., Materials and Methods: We studied 152 patients who underwent heart transplantation between 2001 and 2007. Combined transplantations and retransplantations were excluded. Two groups were considered: emergency transplantations (36 patients, 24%) and elective transplantations. We compared survival and occurrence of infection, primary graft failure (PGF), renal and hepatic failure, respiratory complications, cardiac tamponade, arrhythmias, reoperation, and intensive care unit (ICU) stay., Results: The emergency transplantation group had a greater number of ischemic patients, with a more prolonged cardiopulmonary bypass time, and a larger proportion of donors were women. Overall mortality in the intensive care unit was 2.6%, with no differences between groups. However, emergency procedures were significantly associated with a higher incidence of PGF, need for intraaortic balloon pump, and a more prolonged mechanical ventilation time, as well as a greater number of bacterial infections and a significantly longer ICU stay., Conclusions: In our series, emergency transplantation showed no greater perioperative mortality. We observed a greater number of severe complications, such as PGF, bacterial infection, and more prolonged mechanical ventilation time.

Background: Cardiac allograft vasculopathy (CAV) is the leading cause of death heart transplant (HT) recipients after the first year. We assessed the influence of cardiovascular risk factors (CVRFs) in HT recipients on the development of CAV after 1 year of follow-up., Materials and Methods: From 2001 to 2005, we studied 72 patients who received a HT and survived for at least 1 years. All patients underwent coronary arteriography and intravascular ultrasonography at 1 year after HT. Cardiac allograft vasculopathy was defined as intimal proliferation of 0.5 mm or more. The analyzed CVRFs were age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, and smoking. We also considered the heart disease that was the reason for HT. The statistical tests used in the univariate analysis were the t and chi(2) tests. Logistic regression was performed with the variables obtained at univariate analysis., Results: Mean (SD) recipient age at HT was 51 (9) years. Eighty patients (90.5%) were men. Dyslipidemia was significantly associated with a greater incidence of CAV at 1 year (68.3% vs 41.9%; P = .03). Ischemia, as opposed to all other causes, was also significantly associated with CAV (69.4% vs 44.4%; P = .03). Older age, hypertension, smoking history, and high body mass index were associated with a higher incidence of CAV, albeit without statistical significance. At multivariate analysis, dyslipidemia was the most significant CVRF (P = .045) for the development of CAV., Conclusions: Recipient dyslipidemia is a risk factor for the development of CAV in HT. The remaining traditional CVRFs are more weakly associated with CAV. After HT close monitoring of recipients with pretransplantation CVRFs is essential for early detection of CAV.

Introduction: The side effects of proliferation signal inhibitors (PSIs) have been characterized as a class. However, it would be convenient to assess them according to the molecule., Objective: To assess prospectively the tolerance of PSIs among heart transplant (HT) patients., Patients and Methods: We studied 56 HT patients who sequentially received PSIs to either withdraw (77%) or reduce the dosage of a calcineurin inhibitor; 42 received everolimus (EVE) and 14 sirolimus (SRL). We analyzed the demographic variables, side effects, and need to withdraw the drug during a median follow-up period of 365 days., Results: No differences between groups were observed upon analysis of the clinical and demographic variables when the treatment was changed owing to renal dysfunction (67%) or tumor (32%). No difference between groups was observed over the follow-up period (P = .28). Infection was the most common side effect, 28.6%: EVE, 14.3% versus SRL, 71.4% (P < .0001). Edema occurred in 26.8% of patients: EVE, 14.3% versus SRL, 64.3% (P = .001); diarrhea in 5.4% of patients: EVE, 2.4% versus SRL, 14.3% (P = .15). Treatment was withdrawn in 23.2% of the patients due to intolerance: EVE, 11.9% versus SRL, 57.1% (P < .0001). EVE showed significantly better survival without edema or infections or used for drug withdrawal upon Kaplan-Meier analysis, (P = .01; P = .0005; P = .0097). Only SRL use was shown to be an independent predictor of side effects., Conclusion: Edema and infections are the main problems caused by PSIs. EVE may display a better tolerance profile than SRL.

Introduction: Idiopathic dilated cardiomyopathy (DCM) is, together with ischemic heart disease, the major cause of end-stage heart failure leading to heart transplantation. However, an unknown percentage of patients with this diagnosis has inflammatory foci found in the histopathological study of the explanted heart. This fact suggests an undetected process of acute myocarditis as the cause of cardiac dysfunction., Objective: The objective of this study was to identify clinical and echocardiographic variables related to the presence of myocardial infiltrates, as a potential guide to determine which patients should undergo endomyocardial biopsy in DCM., Materials and Methods: We retrospectively analyzed 161 patients who underwent heart transplantation with a diagnosis of DCM between 1987 and 2007. The presence of inflammatory infiltrates was considered significant when the histopathological study of tissue blocks from the left ventricle showed 1 or more foci per cm(2) of perivascular or interstitial mononuclear or polymorphonuclear cells, whether or not in the presence of cytolysis., Results: Seventeen patients (11%) had these inflammatory histological findings; of them, 6 (35%) showed preponderance of eosinophils and 7 (41%) showed areas of cytolysis. The DCM group with inflammatory infiltrates showed significant differences in terms of younger age (45 +/- 15 vs 50 +/- 11 years; P < .01) and smaller ventricular diameters (P < .05). Male gender was more frequent in this group, and the patients had a poorer clinical status and greater dependence on inotropic drugs., Conclusions: Inflammatory infiltrates are frequently present in DCM explanted hearts. Although there are no relevant clinical variables to identify subclinical myocarditis, these patients are younger and have smaller ventricular diameters and poorer functional status at the time of transplantation.

Introduction: Prolonged catecholamine overstimulation of the myocardium in chronic heart failure causes a reduction in the number and functionality of beta1-adrenoceptors (beta1-AR) of the heart. Desensitization of beta1-AR is mediated by their phosphorylation by a group of cytosolic kinases (G-protein-coupled receptor kinases GRK). In advanced heart failure, an increase in GRK levels associated with the severity of the disease has been observed., Objective: The objective of this study was to analyze messenger RNA (mRNA) levels of beta1-AR in the myocardium of patients who underwent transplantation for advanced heart failure and their correlation with expression of the major cardiac isoenzymes of GRK., Materials and Methods: Myocardial tissue samples were obtained from the left ventricles of 14 explanted hearts of patients who underwent transplantation for dilated (n = 7) and ischemic (n = 7) cardiomyopathy. RT-PCR techniques were used to analyze mRNA levels of beta1-AR and the isoenzymes GRK2, GRK3, and GRK5., Results: We observed a significant correlation between beta1-AR and the 3 subtypes of GRK (R(2) = 0.668, 0.71, and 0.318, respectively)., Conclusions: In patients with advanced heart failure pretransplantation, we observed a significant correlation between beta1-AR and GRK2 and GRK3 levels. GRK5, the subtype predominantly expressed in the myocardium, showed a lesser correlation with beta1-AR levels.

Background: Renal dysfunction is a serious problem after heart transplantation (HT). The objective of this study was to determine the cardiovascular risk factors associated with medium- to long-term dysfunction after HT., Materials and Methods: We studied 247 consecutive patients who underwent HT between January 2000 and September 2006 who survived for at least 6 months. We excluded patients receiving combination transplants, those undergoing repeat HT, and pediatric patients undergoing HT. Mean (SD) follow-up was 72 (42) months. We defined renal dysfunction as serum creatinine concentration greater than 1.4 mg/dL during follow-up. Patients were considered to be smokers if they had smoked during the six months before HT, to have hypertension if they required drugs for blood pressure control, and to have diabetes if they required insulin therapy. Statistical tests included the t test and the chi(2) tests. We performed Cox regression analysis using significant or nearly significant values in the univariate analysis., Results: Mean (SD) age of the patients who underwent HT was 52 (10) years, and 217 (87.9%) were men. Renal dysfunction was detected during follow-up in 135 (54.5%) patients. The significant variables at univariate analysis were smoking (61.4% vs. 43.2%; P = .01) and previous renal dysfunction (94.1% vs 52.7%; P = .001). Nearly significant variables were the presence of hypertension before HT (63.8% vs 51.1%; P = .09) and after HT (58.2% vs 44.8%; P = .082). At multivariate analysis, pre-HT smoking and previous renal dysfunction were significant correlates (P = .04 and P = .01, respectively)., Conclusions: Renal dysfunction is common after HT. In our analysis, the best predictors were pre-HT dysfunction and smoking. Less important factors were advanced age and post-HT hypertension.

Introduction: Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality among heart transplant (HT) patients. Various prophylactic and preemptive treatment regimens have been used for its prevention. We sought to assess the impact of oral valganciclovir on CMV prophylaxis in HT patients., Patients and Methods: A retrospective analysis of 536 consecutive HT patients at our institution allowed selection of subjects eligible for prophylaxis based on CMV serology (donor positive/recipient negative). Treatment compliance, rates of preemptive therapy and treatment for CMV disease were assessed according to prophylactic drug use. If the indication was present, treatment was considered to have been performed., Results: Among 536 patients, 9.8% (n = 53) were eligible for prophylaxis. Seventeen patients (33%) received valganciclovir, with a compliance rate of 94.1%. The remaining 68% received prophylaxis mainly with IV. ganciclovir (5 mg/kg) during their hospital stay followed by oral ganciclovir, with a compliance rate of 57.1% (P = .01). No differences were observed when we analyzed the need for preemptive therapy (0 vs 7%; P = .28) or for treatment of systemic or organ-specific infection (6.3 vs 0%; 6.3 vs 14%, respectively; P = .8)., Conclusion: Oral valganciclovir facilitated treatment compliance in prophylaxis for CMV without being inferior to other prophylactic therapies.

Objective: To assess the incidence of major complications in the postoperative recovery unit and to analyze the associated recipient, donor, and surgical risk factors., Material and Methods: We studied a series of consecutive orthotopic heart transplants carried out in our hospital from 2001 through 2007. Patients who experienced major complications during their stay in the recovery ward were compared with those who did not. Exitus, primary graft failure, severe infection, and need for hemodialysis were considered major complications., Results: One hundred fifty-two patients were enrolled. The mean stay in the recovery unit was 3 days (range, 225-5 days). Thirty-nine patients (26%) developed major complications in the recovery unit and 113 did not. The complications were primary graft failure (20%), infection (12%), and acute renal failure (53%). Patients with and without major complications were significantly different with respect to mean (SD) age (55 [6] vs 50 [12] years, respectively; P=.001), presence of diabetes mellitus (41% vs 14%, P=.0001), classification in New York Heart Association functional class IV/IV status (54% vs 34%, P=.05), emergency transplantation (46% vs 18%, P=.001), mean cardiopulmonary bypass time (145 [66] vs 119 [35], P=.03), pretransplant use of an intra-aortic balloon pump (15% vs 6%, P=.04). Multivariate analysis demonstrated an association between major complications and emergency transplantation (OR, 5.67; P=.001), recipient age over 55 years (OR, 2.99; P=.027), and diabetes mellitus (OR, 2.86; P=.048)., Conclusions: The incidence of major complications in our postoperative recovery unit was 26%. The most common complications were primary graft failure, infection, and acute renal failure. Emergency transplantation, older age, and a diagnosis of diabetes mellitus in the recipient were predictors of complication.

Introduction: Trials of education and support in heart failure patients have shown an improvement in patient prognosis with favorable results in cost-benefit analysis., Objectives: To assess the impact of a telephone support program for heart transplant patients during the first year after transplantation., Patients and Methods: We analyzed 30 consecutive heart transplant patients at our institution, who were randomized to either a standard care group or a group with the additional possibility of direct telephone contact with a cardiologist. We analyzed the time employed answering the calls, the reasons for consultation, and the number of hospital trips avoided., Results: Among the total sample, 15 patients were assigned to the intervention program. Over 194 +/- 103 days, we received 28 calls. The mean call duration was 10.2 +/- 3.9 minutes, with 39.3% of the consultations concerning medication dosages 28.6% lifestyle issues, 25% infectious symptoms, and the remaining 7%, medication side effects. Medication readjustments were made in 33% of the calls; 10.7% of the calls, all for infectious symptoms, required direct medical consultation., Conclusion: Telephone support may be useful to improve therapeutic compliance, adjust the medications, and avoid treatment errors, as well as detect early complications during follow-up. In addition, it may avoid unnecessary medical visits.

Background: Renal failure is one of the primary medium- to long-term morbidities in heart transplant (HT) recipients. To a great extent, this renal deterioration is associated with calcineurin inhibitors, primarily cyclosporine A (CsA). It has been suggested that tacrolimus provides better renal function in these patients. We assessed the medium-term evolution of renal function depending on the calcineurin inhibitor used after HT., Patients and Method: We assessed 40 consecutive HT recipients over one year. Patients were randomized to receive CsA (n = 20) or tacrolimus (n = 20) in combination with mycophenolate mofetil (1 g/12 h) and deflazacort in decreasing dosages. We analyzed demographic variables before HT, creatinine values before and six months after HT and incidence of acute rejection., Results: No demographic, clinical, or analytical differences were observed were between the two groups before HT. Repeated measures analysis of variance of creatinine values showed no significant differences between the two groups (P = .98). Furthermore, no differences were observed in either the incidence of rejection (P = .02) or rejection-free survival (P = .14)., Conclusion: There seems to be no difference in efficacy profile and renal tolerability between CsA and tacrolimus therapy during the first months after HT.

Case Report: A case of chronic follicular conjunctivitis in an infant presenting with ptosis and dacryorrhea is reported. Polymerase chain reaction (PCR) test identified Chlamydia trachomatis as the causative agent. The patient was treated with topic and systemic erythromycin. The infection was probably transmitted during delivery., Discussion: Chronic follicular conjunctivitis in infants is very uncommon in our environment. The most sensitive and specific diagnostic test is PCR. It is necessary to identify the original focus of infection and to provide specific treatment to all the carriers as soon as possible to avoid and prevent chronic complications.

Background: Continuously elevated B-type natriuretic peptide B (BNP) levels are associated with adverse prognosis in heart failure, but this has been less well established in heart transplantation, where medium- to long-term studies are lacking. The purpose of this study was to determine whether BNP levels determined in the first year of transplant have prognostic implications for subsequent outcome., Methods: A retrospective case-control study was carried out in 71 heart transplant patients with a total of 488 biopsies and BNP determinations. Determinations that might raise BNP levels (rejection, high lung pressures, renal dysfunction, depressed ventricular function and graft vascular disease) and those obtained in the first 4 months were excluded. The final analysis included 56 patients with 155 BNP determinations spread over Months 5, 7, 9 and 12. Two groups were made according to the presence of major events after the first year (death, late rejection and ventricular dysfunction associated or not with graft vascular disease): group with events: 13 patients, 37 determinations; group without events: 43 patients, 118 determinations., Results: There were no differences in the clinical profile of the patients. Mean follow-up was 6 years. Mean BNP was higher in the events group for determinations at Month 5 [event: 140 (95), no events: 68 (68); p = 0.01], Month 7 [event: 174 (32), no event: 66 (65); p = 0.002], Month 9 [event: 143 (37), no event: 58 (54); p = 0.002] and Month 12 [event: 126 (55), no event: 48 (37); p = 0.001]. The receiver-operator characteristic (ROC) curve showed that a BNP value of 100 pg/ml classified patients with a sensitivity of 80% and a specificity of 75% (p = 0.0001)., Conclusions: BNP values determined in the first year of transplant might help to distinguish a sub-group of patients with a higher rate of significant complications in long-term follow-up.

The bark of the Mimosa tenuiflora (Willd.) Poiret (Leguminoseae) tree, known as tepescohuite in Mexico, is commonly used in this country and in Central America to elaborate different products for the treatment of skin burns and lesions. The cicatrizing properties of extracts obtained from this bark have been scientifically studied, attributing the main biological activity to its tannin and saponin content. Studies include clinical trials of phytodrugs based on Mimosae tenuiflora bark extracts for treatment of venous leg ulcerations. Recent commercialization of the plant drug Mimosae tenuiflorae cortex requires pharmacognostical information to develop quality-control methods for raw materials and extracts produced with this plant drug. The present paper reports a group of ethnobotanical, morphological, chemical, and molecular studies performed with Mimosae tenuiflora materials obtained by collection in the southeastern Mexican state of Chiapas. Macro- and micro-morphological parameters were established to authenticate the genuine drug that allowed detection of adulterants usually found in commercial samples of this plant material. These morphological characteristics can be used for rapid identification of the drug and are particularly useful in the case of powdered materials. The chemical studies performed demonstrated that tannins represent the major component group in the bark. Its content in genuine tepescohuite is 16% and is mainly composed of proanthocyanidins, a condition permitting a tannin-based chemical-control method for fingerprinting the plant drug. Contrariwise, the saponin concentration in Mimosae tenuiflora bark is extremely low, and its isolation and content evaluation represent a complex procedure that is unsuitable for routine control purposes. Finally, random amplified DNA (RAPD) analysis results a useful tool for obtaining DNA specific markers of Mimosae tenuiflora species which should be useful in future studies involving raw material authentication by molecular methods.

Background: Mammalian target of rapamycin (mTOR) inhibitors are relatively new drugs in the field of cardiac transplantation (HT), hence the need for further study of their secondary effects. We described the nature and incidence of secondary effects of these drugs in a group of HT recipients., Patients and Methods: We studied 23 HT recipients aged 52 +/- 9 years (Male: 91%, body mass index: 27 +/- 3.7, ischemic cardiopathy: 52%, dilated cardiomyopathy: 39%) who were started on an mTOR inhibitor (everolimus: 65%, sirolimus: 35%) as part of their treatment. We have described the secondary effects detected during a follow-up period of 10.7 +/- 6 months., Results: The reasons for starting the drug were renal impairment (65%), tumors (26%), and others (8%). During follow-up, 17% of patients required a dose reduction and 12% required drug withdrawal: edemas: 4%, recurrent infection: 4%, and hemolytic-uremic syndrome: 4%. Drug-attributable edemas presented in 26% of patients. Thirty nine percent suffered an infection that required hospital admission, 89% of which were lung and all bacterial two patients died due to the infection). The mean time to first infection was 5 +/- 6 months. In patients who had a treatment change due to tumors, 50% experienced improvement. We did not detect alterations in cholesterol, triglycerides, creatinine, or leukocytes. There was a nonsignificant trend toward decreased hemoglobin and platelet levels (P = .07 and P = .056, respectively)., Conclusions: Lung infection was the principal complication among our patients treated with mTOR inhibitors. A large percentage required dose reduction (17%) and even drug withdrawal (12%) due to secondary effects.

Introduction: The present study evaluated the clinical and hemodynamic situation of patients with advanced heart failure considered for heart transplantation (HT) to examine the possible impact of prior cardiac disease., Methods: We analyzed the pretransplant clinical, echocardiographic, and hemodynamic parameters of 422 consecutive HT patients. Pediatric and heart plus lung transplants were excluded, as were retransplantations. The results were compared by dividing the patients into three groups according to the background heart disease that led to HT: ischemic heart disease (IHD), dilated myocardiopathy (DMC), or valvular disease., Results: Differences were observed in the baseline characteristics according to the type of heart disease. Male gender, hypertension, and diabetes were more frequent among IHD, while DMC patients tended to be younger. There were no differences in the clinical parameters such as liver and kidney function, in the functional class, or in the need for inotropic treatment over the days prior to transplantation. Likewise, no differences were recorded in the hemodynamic parameters, such as pulmonary pressure, pulmonary vascular resistance, or transpulmonary pressure gradient. As regards the echocardiographic parameters, the patients with DMC showed greater ventricular diameters and lesser ejection fractions for both ventricles., Conclusion: No important differences were recorded in the clinical situation or hemodynamic parameters of patients with advanced heart failure accepted for transplantation, according to the background cardiac disease. This observation could be due to the homogenization by strict transplant waiting list inclusion criteria.

Unlabelled: Dyslipidemia is a common problem among heart transplant (HT) recipients; it is a frequent risk factor in these patients that is exacerbated by immunosuppressive drugs. Statins are effective drugs to treat dyslipidemia in HT recipients, but control is suboptimal in some patients. Ezetimibe acts through inhibition of the enterohepatic recirculation, a mechanism different from but complementary to statins. Our objective was to assess the effect of the addition of ezetimibe to statin therapy among a population of HT patients., Patients and Methods: We included 19 stable patients on statin therapy with suboptimal control of cholesterol. Determinations were performed at baseline on statins and at 6 months (statins + ezetimibe). The analyzed variables were total cholesterol and fractions, triglycerides, cyclosporine levels, CPK, SGOT/SGPT, and bilirubin. The statistics were Student's t test for paired samples., Results: The overall mean age was 59 +/- 9 years with 95% males and mean BMI 27.5 +/- 3.5. The time since HT was 7 +/- 3 years. The reason for HT included ischemic heart disease in 68%. Pre-HT risk factors included in arterial hypertension in 32% and insulin-dependent diabetes mellitus in 10%, Dyslipidemia occurred in 68%; hypertriglyceridemia in 16% and hyperuricemia in 21%. Immunosuppression was cyclosporine in 100% and steroids in 94%. Type of lipid-lowering agent was simvastatin in 5%; pravastatin, 32%; atorvastatin, 58%; fibrates, 10%. The ezetimibe dose was 10 mg/day in 95% of cases. When ezetimibe was added we observed differences in total cholesterol values (total cholesterol at baseline: 279 +/- 74, total cholesterol with ezetimibe: 198 +/- 47 mg/dL; P = .0001) and LDL-cholesterol values (LDL-cholesterol at baseline: 171 +/- 69, LDL-cholesterol with ezetimibe: 109 +/- 41 mg/dL; P = .001). The remaining variables did not show significant differences., Conclusion: The addition of ezetimibe to statin therapy among heart transplant patients was effective to control dyslipidemia and showed an excellent safety profile.

Introduction: Smoking is an important risk factor in any population group. According to previous studies, having been a smoker before heart transplantation (HT) confers a greater likelihood of developing any type of tumor or other complication after HT. Our objective was to determine the impact of having been a smoker before HT on survival, respiratory complications during the postoperative period, and long-term tumor development., Materials and Methods: After excluding combined transplantations, pediatric transplantations, and retransplantations, we retrospectively reviewed 288 HT performed between November 1987 and September 2006. We divided patients into nonsmokers (including those who quit smoking more than 1 year before HT (n = 163), exsmokers for less than 1 year (n = 76), and those who smoked until HT (n = 49). The statistical tests were chi-square, Student t, analysis of variance (ANOVA), and Kaplan-Meier curves., Results: There were more male patients among smokers and exsmokers than nonsmokers (93.9% vs 96.1% vs 82%, respectively; P = .003). There were no differences in baseline characteristics between the groups. Exsmokers remained intubated for a longer time than smokers or nonsmokers (33.4 +/- 44.6 vs 14.2 +/- 7.3 vs 17.9 +/- 19.2, respectively; P = .05). We observed the same trend in recovery unit stay (7.9 +/- 10.5 days vs 4.4 +/- 1.88 days vs 4.84 +/- 3.49 days, respectively; P = .021). The development of any type of tumor was also more frequent among smokers and exsmokers, although not significantly. The survival rate was similar in nonsmokers and exsmokers, although higher than in smokers (89.57 vs 92.11% vs 81.63%, respectively; P = .031). We did not observe differences in the causes of death., Conclusions: Patients who smoke or have smoked until shortly before HT showed a poorer prognosis and a longer recovery unit stay. There was also a trend to increased tumor development.

Objective: The objective of this study was to compare baseline characteristics and long-term survival among patients undergoing heart transplantation (HT) according to the 3 main types of prior heart disease: ischemic, idiopathic dilated cardiomyopathy (IDC), and valvular., Materials and Methods: Four hundred twenty-three HTs performed between 1989 and 2005 were included. We excluded pediatric transplantation, retransplantations, combined transplantations (lung and kidney), and transplantations due to heart diseases other than ischemic, IDC, and valvular. Baseline characteristics of the recipients were analyzed, as well as short-term and long- term survival by groups. Analysis of variance (ANOVA) was used for continuous variables and chi-square was used for categorical variables. Survival analysis was computed using Kaplan-Meier curves and the log-rank test, as well as multivariate analysis using logistic regression., Results: The ischemic and valvular heart disease groups were older and had a more frequent history of prior heart surgery and circulatory support at the time of transplantation compared with the IDC group. The incidence of arterial hypertension and dyslipidemia was higher among ischemic heart disease recipients. Survival rates at 30 days did not show significant differences (ischemic, 88%; IDC, 93%; and valvular; 84%; P = .21). Long-term survival rates were greater in the IDC than in the valvular or ischemic heart disease groups (75% vs 65% and 62%, respectively; P = .021). The multivariate analysis showed an association between the IDC group and long-term survival (odds ratio [OR], 0.55; 95% confidence interval [CI] 0.35-0.89; P = .015)., Conclusions: (1) Patients showed a different clinical profiles depending on their pretransplantation heart disease. (2) There were no differences in early mortality between the groups. (3) Long-term survival was significantly greater among IDC transplant recipients and similar in ischemic and valvular heart disease transplant recipients.

Unlabelled: The number of congenital heart disease (CHD) patients transplanted to date is small. The results are comparable to those undergoing heart transplantation (HT) for other etiologies. However, advances in pediatric surgery over recent years (eg, the Fontan procedure) has increased the demand for HT by a growing number of children who reach adulthood and who also have a different profile. We analyzed the clinical profile and survival of our CHD patients compared with other etiologies., Materials and Methods: From July 17, 1991 to December 31, 2006, eight HT were performed in our center for CHD. A descriptive study determined the baseline characteristics and survival of these patients, compared with those of the overall transplant group and other subgroups (dilated cardiomyopathy, ischemic heart disease)., Results: Mean age was 26 years. Four (50%) CHD patients were diagnosed with single-ventricle anatomy, associated or not with other lesions; none had been operated with the Fontan procedure. Two patients died prematurely. Early, 1-, and 10-year survival was 75% at each time point. Early, 1-, and 10-year survival in the group with other diagnoses was 90%, 78%, and 60%, respectively, and in the dilated cardiomyopathy group it was 94%, 86%, and 72%, respectively., Conclusion: The current number of CHD transplant patients was small and young. The most common etiology was single-ventricle anatomy without a prior Fontan operation. Overall survival was comparable to HT for dilated cardiomyopathy.