Prevalence and Clinical Characteristics of HIV Type 1-Infected Patients Receiving Dialysis in Spain: Results of a Spanish Survey in 2006: GESIDA 48/05 Study

End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

Detection of suspected placental invasion by MRI: Do the results depend on observer' experience?

PURPOSE: To evaluate the diagnostic value of previously described MR features used for detecting suspected placental invasion according to observers' experience. MATERIALS AND METHODS: Our population included 25 pregnant women (mean age 35.16) investigated by prenatal MRI (1.5T, T1- and T2-weighted MR-sequences without i.v. contrast), among them 12 with histopathologically proven placental invasion and 13 women (52%) without placental invasion used as control group. Two senior and two junior radiologists blindly and independently reviewed MR-examinations in view of 6 previously defined MR-features indicating presence and degree of placental invasion (placenta increta, accreta or percreta). For each reader the sensibility, specificity, and receiver operating curve (ROC) were calculated. Interobserver agreements between senior and junior readers were determined. Stepwise logistic regression was performed including the 6 MR-features predictive of placental invasion. RESULTS: Demographics between both groups were statistically equivalent. Overall sensitivity and specificity for placental invasion was 90.9% and 75.0% for seniors and 81.8% and 61.8% for juniors, respectively. The best single MR-feature indicating placental invasion was T2-hypointense placental bands (r(2)=0.28), followed by focally interrupted myometrial border, infiltration of pelvic organs and tenting of the bladder (r(2)=0.36). Interobserver agreement for detecting placental invasion was 0.64 for seniors and 0.41 for juniors, thus substantial and moderate, respectively. Seniors detected placental invasion and depth of infiltration with significantly higher diagnostic certitude than juniors (p=0.0002 and p=0.0282, respectively). CONCLUSION: MRI can be a reliable and reproducible tool for the detection of suspected placental invasion, but the diagnostic value significantly depends on observers' experience.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Improvement in growth after two years of growth hormone therapy in very young children born small for gestational age and without spontaneous catch-up growth: results of a multicenter, controlled, randomized, open clinical trial.

CONTEXT GH treatment is effective in children born small for gestational age (SGA); however, its effectiveness and safety in very young SGA children is unknown. OBJECTIVE The aim was to analyze the outcome of very young SGA children treated with GH and followed for 2 yr. The results after 24 months of treatment, compared with a control group without treatment during 12 months followed by 12 months of treatment, are shown. DESIGN We performed a multicenter, controlled, randomized, open trial. SETTINGS The pediatric endocrinology departments of 14 public hospitals in Spain participated in the study. PATIENTS Seventy-six children, aged 2-5 yr born SGA and without catch-up growth, were studied. INTERVENTION Children received GH at 0.06 mg/kg.d for 2 yr (group I) or were followed for 12 months with no treatment and then treated for 12 months (group II). MAIN OUTCOME MEASURES Age, general health status, pubertal stage, bone age, height, weight, biochemical and hormonal analyses, and adverse side effects were determined at biannual check-ups. RESULTS The mean height sd score gain for chronological age in children treated for 24 months (group I) was 2.10, whereas in those treated only during the last 12 months (group II) was 1.43. In both groups, children under 4 yr of age had the greatest gain in growth velocity. No significant acceleration of bone age or side effects related to treatment was seen. CONCLUSION Very young SGA children without spontaneous catch-up growth could benefit from GH treatment because growth was accelerated and no negative side effects were observed.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: Results from the global valve-in-valve registry.

BACKGROUND Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Hourly activity of Lutzomyia neivai in the endemic zone of cutaneous leishmaniasis in Tucumán, Argentina: preliminary results

In the present work, the hourly activity of Lutzomyia neivai was studied in the southern part of the province of Tucumán, Argentina, in an area of transmission of cutaneous leishmaniasis during two months of higher activity. In addition, the variables that influenced the abundance of Lu. neivai were evaluated. A total of 1,146 individuals belonging to Lu. neivai (97%) and Lutzomyia migonei (3%) were captured. The hourly activity of Lu. neivai was mainly nocturnal, with a bimodal pattern in both months. In January, the variable that most influenced the abundance of Lu. neivai was the temperature, whereas in April, that variable was humidity. These results may contribute to the design of anti-vectorial control measures at a micro-focal scale.

Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of intestinal healing.

The second scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal healing for the disease course of inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms, markers for disease prediction, detection and monitoring of intestinal healing, impact of intestinal healing on the disease course of IBD as well as therapeutic strategies. The results of this workshop are presented in four separate manuscripts. This section describes basic mechanisms of intestinal healing, identifies open questions in the field and provides a framework for future studies.

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel.

BACKGROUND: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. METHODS: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). RESULTS: Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as "appropriate" by the panellists, whereas a radiological evaluation was considered as being of "uncertain" appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. CONCLUSION: A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

Social inequalities and mortality in Europe-results from a large multi-national cohort

BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

Measurements of eye lens doses in interventional radiology and cardiology: Final results of the ORAMED project

Within the ORAMED project (Optimization of Radiation Protection of Medical Staff) a coordinated measurement program for occupationally exposed medical staff was performed in different hospitals in Europe (www.oramed-fp7.eu). The main objective was to obtain a set of standardized data on extremity and eye lens doses for staff involved in interventional radiology and cardiology and to optimize radiation protection. Special attention was given to the measurement of the doses to the eye lenses. In this paper an overview will be given of the measured eye lens doses and the main influence factors for these doses. The measured eye lens doses are extrapolated to annual doses. The extrapolations showed that monitoringof the eye lens should be performed on routine basis.

Primary renal lymphoma: long-term results of two patients treated with a chemotherapy + rituximab protocol.

Primary renal lymphoma (PRL) is a rare disease of which the etiology and pathogenesis remain controversial, and there is currently no standard treatment for it. We present the results of a long-term followup of two patients who were diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine, prednisolone and rituximab (CHOP + R) regimen. Both patients reached a complete response, and there is no evidence of recurrence after 4.5- and 5-year followup periods. Based on our experience and other recently published studies, we recommend the combination of CHOP + rituximab as the elective treatment for this disease. To our knowledge, this is the longest followup period with a complete response that has been reported with this modality of treatment.

Treatment of an Aedes aegypti colony with the Cry11Aa toxin for 54 generations results in the development of resistance

To study the potential for the emergence of resistance in Aedes aegypti populations, a wild colony was subjected to selective pressure with Cry11Aa, one of four endotoxins that compose the Bacillus thuringiensis serovar israelensis toxin. This bacterium is the base component of the most important biopesticide used in the control of mosquitoes worldwide. After 54 generations of selection, significant resistance levels were observed. At the beginning of the selection experiment, the half lethal concentration was 26.3 ng/mL and had risen to 345.6 ng/mL by generation 54. The highest rate of resistance, 13.1, was detected in the 54th generation. Because digestive proteases play a key role in the processing and activation of B. thuringiensis toxin, we analysed the involvement of insect gut proteases in resistance to the Cry11Aa B. thuringiensis serovar israelensis toxin. The protease activity from larval gut extracts from the Cry11Aa resistant population was lower than that of the B. thuringiensisserovar israelensis susceptible colony. We suggest that differences in protoxin proteolysis could contribute to the resistance of this Ae. aegypti colony.