Cytomegalovirus Infection Monitoring Based on Interferon Gamma Release Assay in Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most common viral infection after kidney transplantation and is associated with significant morbidity and mortality. Recent studies showed that CMV-specific CD8+ T cells play the crucial role in protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN-γ) release assay (IGRA test) that measures the IFN-γ response to a range of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility of QF-CMV assay to predict CMV infection in kidney transplant recipients and evaluated if reactive result in QF-CMV test could be predictor of the duration of treatment. METHODS: We studied 75 renal transplant recipients who had IGRA testing just before transplantation. The donor and recipient variables were reported from the clinical history. The variables related to transplantation were collected from transplantation process data and included CMV infection or disease, CMV treatment, and immunosuppressive treatment. Laboratory variables were C3-C4 complement fractions and DNA quantification of CMV. RESULTS: Fifty percent of patients had CMV infection, and 35.9% had CMV disease. The time of negativization of CMV DNA was 56.61 ± 23.5 days. Univariate analysis related to CMV infection only showed a statistically significant relation with thymoglobulin treatment (P = .001). Statistically significant variables in relation with CMV infection incidence were donor serology (P = .044) and thymoglobulin treatment (P = .004). The probability of CMV infection was lower with positive IGRA assay (P = .025). CONCLUSION: We found that IFN-γ response measured by QF-MV is a protective factor against CMV infection in post-transplantation kidney recipients.

Predictive factors of infection in the first year after kidney transplantation.

BACKGROUND: Infectious disease, a complication favored by immunosuppression, is the main cause of 1st-year mortality in solid organ transplantation. In renal transplant recipients (RTRs), urinary tract infection (UTI) is the most common, and the microorganisms that are isolated depend on chronology. METHODS: We present an observational study comprising 129 RTRs from January 2010 to December 2011 who were followed during the 1st year after transplantation. We analyzed occurrence of infections, predisposing factors, timing, severity, site of infection, and microorganisms. RESULTS: The patients had a total of 424 infectious episodes during the 1st year (3.29 episodes/patient/year). The predominant focus was the urinary tract, with at least 1 episode in 69.8% of patients. Bacteremia was recorded in 25.6% of patients and surgical wound infection in 20.9%. Cytomegalovirus infection or disease was diagnosed in 46.5%. Severe infections occurred in 30.2%. The predominant pathogen was E. coli. There was a significant correlation between hospital stay and the number of infections (P = .000; r = 0.407) and between body mass index and hospital stay (P = .001; r = 0.282). Severe infections were more frequent in diabetics, patients with a double-J stent, and those treated with basiliximab. Patients with cytomegalovirus replication had a higher number of infections (4.1 ± 1.2 vs 2.5 ± 5; P = .000) and significantly higher annual serum creatinine (1.65 ± 5.7 vs 1.31 ± 1.3 mg/dL; P = .003). CONCLUSIONS: The prevalence of infections in the 1st year after kidney transplantation is very high, occurring mainly in the early period, in the urinary tract, and due to E. coli. Cytomegalovirus replication is associated with a higher number of infections and higher serum creatinine at 1 year. Body mass index is a predictor of early infection and of bacteremia in the post-transplantation period. Basiliximab induction and having a double-J stent were predictors of severe infections.

Ambulatory blood pressure monitoring in kidney transplant patients: RETENAL study.

Hypertension is common following renal transplantation, affecting up to 80% of transplant recipients. It is generally accepted that hypertension is associated with poor graft survival and reduced life expectancy, contributing to increased cardiovascular risk factors and mortality rates. The aim of the study was to compare the blood pressure (BP) control in kidney transplant patients through the use of ambulatory BP monitoring (ABMP) versus office BP measurements (oBP). A multicenter, cross-sectional, observational study was conducted in 30 nephrology/kidney transplant units. Eligible patients included hypertensive cadaveric kidney transplant recipients aged <70 years, with a functioning kidney for at least 1 year and with an estimated glomerular filtration ≥30 mL/min/1.73 m(2) and a serum creatinine < 2.5 mg/dL. Recorded data included demographic characteristics, oBP, and ABPM and labroatory investigations. The 868 patients showed a mean recipient age of was 53.2 ± 11.6 years and mean follow-up after transplantation, 5.5 ± 2.8 years. Mean systolic and diastolic oBP were 140.2 ± 18 and 80.4 ± 10 mm Hg, respectively. Seventy-six percent of patients had oBP higher than or equal to 130/80 mm Hg. Mean 24 hour ABPM were 131.5 ± 14 and 77.4 ± 8.7 mm Hg for systolic and diastolic BP, respectively. Using the ABPM, we observed that 36.5% of subjects were controlled (mean 24-hour BP < 130/85 mm Hg). The two methods (oBP and ABPM) showed significant agreement. After ABPM, 65% of patients diagnosed as true controlled hypertension were considered to have white-coat RH. In clinical practice ABPM may help for better adjustment of drugs for adequate BP control.

Fetal echocardiography at 11-13 weeks by transabdominal high-frequency ultrasound.

OBJECTIVES: To assess the accuracy of fetal echocardiography at 11-13 weeks performed by well-trained obstetricians using a high-frequency linear ultrasound transducer. METHODS: Fetal echocardiography was performed by obstetricians immediately before chorionic villus sampling for fetal karyotyping at 11-13 weeks. Digital videoclips of the examination stored by the obstetrician were reviewed offline by a specialist fetal cardiologist. RESULTS: The obstetrician suspected 95 (95%) of the 100 cardiac defects identified by the fetal cardiologist and made the correct diagnosis in 84 (84%) of these cases. In 54 fetuses, the defect was classified as major and in 46 it was minor. In 767 (86.6%) cases, the heart was normal and in 19 (2.1%) the views were inadequate for assessment of normality or abnormality. A subsequent second-trimester scan in the normal group identified major cardiac defects in four cases. Therefore, the first-trimester scan by the obstetricians and cardiologists identified 54 (93.1%) of the 58 major cardiac defects. CONCLUSIONS: A well-trained obstetrician using high-resolution ultrasound equipment can assess the fetal heart at 11-13 weeks with a high degree of accuracy.

Semi-automated system for measurement of nuchal translucency thickness.

OBJECTIVE: To estimate intersonographer and intrasonographer variance components of fetal nuchal translucency (NT) thickness measurement using the traditional manual approach and a new semi-automated system. METHODS: A semi-automated method was developed for measurement of the NT. In this method, the operator places an adjustable box over the relevant area at the back of the fetal neck. The system draws a line through the center of the nuchal membrane and another line at the edge of the soft tissue overlying the cervical spine. The system then identifies the largest vertical distance between the two lines. The images of 12 fetuses at 11-13 weeks of gestation satisfying the guidelines of The Fetal Medicine Foundation for measurement of NT were selected. They were exported in DICOM format from the ultrasound system, and four versions of each image were stored under different names. The resulting 48 images were presented in random order for electronic assessment. A total of 20 sonographers measured the NT in each set of 48 pictures, twice using the semi-automated system and twice using the manual system, according to a randomized block design. Within- and between-operator variance components were estimated. Relative biases were assessed by comparing the means from the two methods. RESULTS: The estimated between-operator SD using the semi-automated method was 0.0149 mm compared with 0.109 mm for the manual method. The respective within-operator SD values were 0.05 mm and 0.126 mm. The intraclass correlation coefficients for different sonographers measuring the same images were 0.98 and 0.85 for the semi-automated method and the manual method, respectively. CONCLUSION: The measurement of fetal NT is more reliable when a semi-automatic approach is used rather than the traditional manual method.

Frontomaxillary facial angle in fetuses with spina bifida at 11-13 weeks' gestation.

OBJECTIVE: To determine whether in fetuses with open spina bifida at 11-13 weeks' gestation the frontomaxillary facial angle is decreased. METHODS: The frontomaxillary facial angle was measured in 20 fetuses with open spina bifida and in 100 normal controls matched for crown-rump length (CRL) at 11 + 0 to 13 + 6 weeks and the values in the two groups were compared. RESULTS: In the control group the frontomaxillary facial angle decreased significantly with CRL from a mean of 84.0 degrees at a CRL of 45 mm to 76.5 degrees at a CRL of 84 mm (SD, 3.26 degrees). In the spina bifida group the mean frontomaxillary facial angle, corrected for CRL, was 9.9 degrees lower than in the controls and it was below the 5(th) centile in 18 (90%) of the cases (P < 0.0001). CONCLUSIONS: In fetuses with open spina bifida at 11-13 weeks' gestation the frontomaxillary facial angle is decreased and this measurement may be useful in early screening for this abnormality.

Púrpura fulminante posvaricelosa: potencialmente mortal / Post-varicella purpura fulminans: Potentially fatal

Aunque la varicela suele ser una enfermedad benigna, algunas complicaciones pueden ser mortales, como la púrpura fulminante posvaricelosa. Su mecanismo fisiopatogénico se explica por la producción de anticuerpos para las proteínas C y S de la cascada de la coagulación, lo que puede tener consecuencias funestas con la producción de coagulopatía de consumo en personas con déficits parciales de estas proteínas. El tratamiento es sintomático y consiste básicamente en la administración de plasma fresco congelado (para suplir las proteínas que se consumen), de antitrombina III y heparinización (para tratar la producción de trombos) y de antiinflamatorios, como los corticoides; sin embargo, se están introduciendo tratamientos nuevos, como la prostaglandina E1 intravenosa y la prostaciclina (AU)

Although varicella is usually a benign disease, some of its complications, such as post-varicella purpura fulminans, can be fatal. Its pathophysiological mechanism is caused by the production of antibodies to protein C and protein S in the coagulation cascade. This could have fatal consequences for those patients with partial deficiency of these proteins that develop disseminated intravascular coagulation. Treatment is symptomatic: fresh frozen plasma to treat protein depletion, antithrombin III and heparinization against thrombus formation, and anti-inflammatory drugs (steroids). However, new therapies, such as prostaglandin E1 IV and prostacyclin, are being introduced (AU)

[Post-varicella purpura fulminans: potentially fatal]. / Púrpura fulminante posvaricelosa: potencialmente mortal.

Although varicella is usually a benign disease, some of its complications, such as post-varicella purpura fulminans, can be fatal. Its pathophysiological mechanism is caused by the production of antibodies to protein C and protein S in the coagulation cascade. This could have fatal consequences for those patients with partial deficiency of these proteins that develop disseminated intravascular coagulation. Treatment is symptomatic: fresh frozen plasma to treat protein depletion, antithrombin III and heparinization against thrombus formation, and anti-inflammatory drugs (steroids). However, new therapies, such as prostaglandin E1 IV and prostacyclin, are being introduced.

Left ventricular structure and function in long-term kidney transplantation: the influence of glucose metabolism and oxidative stress.

Impaired cardiac structure and function are fundamental components of cardiovascular disease, leading to morbidity, mortality, and graft loss after renal transplantation. The aim of this study was to describe and determine the factors involved in these cardiac abnormalities, paying special attention to the role of glucose metabolism and oxidative stress. We studied 54 long-term, nondiabetic recipients with no valvulopathy who underwent an echocardiographic examination and simultaneous biochemical determinations of lipid profile, hemoglobin A1c (HbA1c), and various oxidative stress parameters: malondialdehyde, superoxide dismutase, total glutathione, and isoprostanes. We calculated the left ventricular mass index (LVMI) and ejection fraction and the peak velocity of early rapid filling to peak velocity of atrial filling (E/A) ratio. Left ventricular hypertrophy (LVH), systolic dysfunction, and diastolic dysfunction (LVDD) were present in 25.9%, 5.6%, and 59.25% of the patients, respectively. The mean blood pressure (MBP) was higher and the hemoglobin lower among patients with LVH, which was related to the age of the patients. We observed a significant negative association of the E/A ratio-used as an index of LVDD-with HbA1c (r = -.448, P = .002) and age (r = -.57, P = .000) and a positive association with the level of total glutathione (r = .322, P = .029). Multiple regression analysis of the E/A ratio showed significance only for HbA1c but not for MBP or LVMI. These results suggested a possible causal influence of subclinical glucose metabolism impairment as detected by HbA1c on the presentation of LVDD via the impaired oxidative stress status, independent of blood pressure control or LVH grade.

The socio-economic burden of asthma is substantial in Europe.

BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.

Changes in the use of anti-asthmatic medication in an international cohort.

The aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4-3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5-4.5%). In the sample with asthma in both surveys (n=423), the use of inhaled corticosteroids increased by 12.2% (6.6-17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma.

[Association between the forced midexpiratory flow/forced vital capacity ratio and bronchial hyperresponsiveness]. / Asociación entre el cociente FEF(25-75%)/FVC y la hiperreactividad bronquial.

OBJECTIVE: A long-standing hypothesis is that a low ratio of airway caliber to lung size is associated with bronchial hyperresponsiveness (BHR). The aim of our study was to measure the association between airway caliber relative to lung size (expressed as the ratio between forced expiratory flow, midexpiratory phase, divided by forced vital capacity [FEF(25%-75%)/FVC]) and BHR measured by a methacholine challenge test, adjusting for age, height, sex, smoking history, geographic area, respiratory symptoms, and baseline forced expiratory volume in 1 second (FEV1). MATERIAL AND METHODS: We carried out a multicenter cross-sectional study of the general Spanish population in 2647 subjects from the European Community Respiratory Health Survey (ECRHS I). The ECRHS questionnaire was administered, total and specific immunoglobulin E were measured, and skin tests, spirometry, and a methacholine challenge test were performed. RESULTS: We show the relationship of the various clinical and sociodemographic variables with the 2 parameters indicative of a positive methacholine test. The lower the FEF(25%-75%)/FVC ratio was, the greater the risk of HRB, after adjustment for variables (odds ratio [OR]=0.09; 95% confidence interval [CI], 0.04-0.018 for the concentration provoking a 20% decrease in FEV1, and OR=0.06; 95% CI, 0.03-0.12 for the dose provoking a 20% decrease in FEV1). CONCLUSIONS: There is a significant association between the FEF(25%-75%)/FVC ratio and BHR after adjustment for age, atopy, smoking, geographic area, respiratory symptoms, and initial FEV1.

Broncoespasmo en relación con heroína inhalada / Bronchospasm by heroin inhalation

No disponible

Sensitization to individual allergens as risk factors for lower FEV1 in young adults. European Community Respiratory Health Survey.

BACKGROUND: Atopy may impair ventilatory function, but results are controversial. We assess the association between individual reactivity to allergens and the level of baseline maximal one-second forced expiratory volume (FEV1), by smoking and respiratory symptoms. METHODS: The 1472 participants (response 44.5%) of the five Spanish areas of the European Community Respiratory Health Survey (ECRHS) who performed respiratory function tests, skin prick tests and/or specific IgE against common aeroallergens (e.g. mites, pets, mould, pollens) are included. Bronchial hyperreactivity (BHR) was measured with a methacholine challenge. RESULTS: After adjusting for BHR and smoking, in addition to the other allergens, skin reactivity to Alternaria (-208 ml; 95% CI :-451, 35) and IgE antibodies against cat (-124 ml; 95% CI:-269, 21) and Timothy grass (-115 ml, 95% CI:-190, -40) were associated with a decrease in FEV1 in females. Among males, skin reactivity to olive showed the strongest association (-111 ml; 95% CI: -261, 38). The associations were stronger in females. Smoking modifies the association for Alternaria and cat (P for interaction < 0.05). While cat is associated with a decrease in FEV1 in current smokers (-190 ml), Alternaria (-336 ml) was associated among never smokers. The exclusion of subjects with asthma symptoms, or adjustment for respiratory symptoms, led to similar results. CONCLUSIONS: We conclude that immunoresponse to individual allergens (particularly outdoor) is associated with the level of FEV1, and this association occurred independently of asthma, and in smokers and non-smokers, which may be of interest in natural history of chronic obstructive pulmonary disease (COPD).

[Factors associated with the development of atopy in young adults]. / Factores asociados al desarrollo de atopia en adultos jóvenes.

BACKGROUND: To determine the risk factors for the development of atopy in Spanish young adults. SUBJECTS AND METHODS: Case-control study over prevalent cases. Carried out in general population between the ages of 20 to 44 years old. Spanish participants of the ECRHS, a random representative sample of Spanish young adults (n = 16,884), and a 20% randomised subsample made by those who answered to a short respiratory questionnaire and had atopy assessed, was studied. Atopy was defined as having serum specific IgE positivity to the following aeroallergnes: cat dander, Cladosporium herbarum, Dermatophagoides pteronyssinus, Parietaria judaica and Phleum pratense. RESULTS: Several factors had a statistically significant effect. In addition to male gender and lower age, maternal allergy (OR = 1.63; 95% CI = 1.11-2.40), having allergic siblings (OR = 1.40; 95% CI = 1.06-1.90) and a higher educational level (OR = 1.69; 95% CI = 1.22-2.34) were associated with the presence of high levels of specific IgE in our sample. Moreover, having had older siblings, especially older brothers appears to be a protective factor to the development of atopy but not in a statistically significant way, while having had pet birds during childhood appears to enhance the risk. CONCLUSIONS: In addition to the familial variables that indicates both environmental and genetic factors, educational level seems to have low degree of association with atopy; this feature shows that variables related with life style are involved in atopy development.

[European Asthma Study. Identifying and treating young adults with epidemiological criteria for asthma in five areas of Spain. Spanish Group of the European Asthma Study]. / Estudio Europeo del Asma. Identificación y tratamiento de individuos con criterios epidemiólogicos de asma en adultos jóvenes de cinco áreas españolas. Grupo Español del Estudio Europeo del Asma.

BACKGROUND AND OBJECTIVES: Asthma's great impact on public health stems from its chronicity and to high prevalence among all age groups and both sexes. To estimate the appropriateness of treatment and management of asthma in Spain during the period of 1991 and 1992, we analyzed data from the European Community Respiratory Health Survey (ECRHS). METHOD: The ECRHS was undertaken with a random sample of 20-to-44-year-olds in Albacete, Barcelona, Galdakao, Huelva and Oviedo. In total, 181 individuals with asthma were identified. Current asthma was defined as the presence of respiratory symptoms associated with asthma within the past 12 months and a positive methacholine challenge test. RESULTS: Subjects who were unaware of having asthma made up 57.5% (CI: 49.9-64.8%), and 35.9% (CI: 27.9-42.3%) were not following any specific treatment. Among asthmatics who reported having continuous or frequent respiratory symptoms, 25.9% (CI: 15.3-39.0%) were not following any treatment. CONCLUSION: Over half the individuals with asthma in 1991 to 1993 were unaware of having the disease at the time of the study or of ever having had it, and approximately one third were not in treatment. The delivery of appropriate treatment in asthma generally, and in asthma with continuous or frequent respiratory symptoms, was markedly inadequate during the period studied.

Pulmonary ventilatory defects and occupational exposures in a population-based study in Spain. Spanish Group of the European Community Respiratory Health Survey.

We assessed the association between occupational exposures and symptoms of chronic bronchitis and pulmonary ventilatory defects in a general population-based study of five areas in Spain. This study forms part of the European Community Respiratory Health Study (ECRHS). Subjects (n = 1,735; age range, 20-44 yr; 52.4% of those initially selected) completed a respiratory questionnaire on symptoms and occupation and underwent baseline spirometry. Occupation was translated with an ad hoc developed job-exposure matrix (EM) into none, low, and high exposure to biological dust, mineral dust, and gases and fumes. Exposure to high levels of biological dust was associated with cough for more than 3 mo (odds ratio [OR], 1.9; p = 0.07), a reduction in FEF(25-27) to 478 ml/s (SD 178), and a reduction in FEV1 to 151 mL (SD 71). These associations remained after excluding subjects with asthma symptoms or bronchial responsiveness. Smokers tended to have a higher risk for respiratory symptoms, but smoking did not modify the association of occupation with pulmonary function. Exposure to mineral dust and gases/fumes was less consistently related to pulmonary function or to respiratory symptoms and this association further decreased after excluding subjects with asthma. In conclusion, exposure to high levels of biological dust in young adults is associated with symptoms of chronic bronchitis and pulmonary ventilatory defects, independently of asthma and smoking.