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Biallelic variants in PPA2 gene cause a rare but lethal mitochondrial disorder. We describe the first four cases reported in Spain of PPA2 disease in two unrelated families. We have conducted a revision of the clinical history, necropsies, and postmortem genetic testing from probands, and clinical evaluation, genetic testing and blood transcript analysis in family members. All the cases harbored biallelic PPA2 variants in compound heterozygous status. Two brothers from family 1 suffered sudden death after a small first intake of alcohol in 2013 and 2022. The sister remains alive but affected with cardiomyopathy, extensive scar on cardiac imaging, and high sensitivity to alcohol intake. The three siblings carried PPA2 c.290A > G (p.Glu97Gly) novel missense variant and PPA2 c.513C > T (p.Cys171 = ) altering splicing site variant, both probably leading to mRNA degradation based on in-silico and transcript analyses. A teenager from family 2 suffered sudden death after a small intake of alcohol in 2018 and carried PPA2 c.683C > T (p.Pro228Leu) missense and PPA2 c.980_983del (p.Gln327fs) novel frameshift variant, both probably leading to abnormal protein structure. All cases were asymptomatic until adolescence. Furthermore, the sister in family 1 has survived as an asymptomatic adult. PPA2 disease can manifest as cardiac arrest in the young, especially after alcohol exposure. Our results show that PPA2 deficiency can be related to different pathogenicity mechanisms such as abnormal protein structure but also mRNA decay caused by synonymous or missense variants. Strict avoidance of alcohol consumption and early defibrillator implantation might prevent lethal arrhythmias in patients at risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Modern classification and categorization of individuals' health requires personalized variables such as nutrition, physical activity, lifestyle, and medical data through advanced analysis and clustering methods involving machine learning tools. The objective of this project was to categorize Mediterranean dwellers' health factors and design metabotypes to provide personalized well-being in order to develop professional implementation tools in addition to characterizing nutritional and lifestyle features in such populations. Materials and Methods: A two-phase observational study was conducted by the Pharmacists Council to identify Spanish nutritional and lifestyle characteristics. Adults over 18 years of age completed questionnaires on general lifestyle habits, dietary patterns (FFQ, MEDAS-17 p), physical activity (IPAQ), quality of life (SF-12), and validated well-being indices (LS7, MEDLIFE, HHS, MHL). Subsequently, exploratory factor, clustering, and random forest analysis methods were conducted to objectively define the metabotypes considering population determinants. Results: A total of 46.4% of the sample ( n = 5496) had moderate-to-high adherence to the Mediterranean diet (>8 points), while 71% of the participants declared that they had moderate physical activity. Almost half of the volunteers had a good self-perception of health (49.9%). Regarding lifestyle index, population LS7 showed a fair cardiovascular health status (7.9 ± 1.7), as well as moderate quality of life by MEDLIFE (9.3 ± 2.6) and MHL scores (2.4 ± 0.8). In addition, five metabotype models were developed based on 26 variables: Westernized Millennial (28.6%), healthy (25.1%), active Mediterranean (16.5%), dysmetabolic/pre-morbid (11.5%), and metabolically vulnerable/pro-morbid (18.3%). Conclusions: The support of tools related to precision nutrition and lifestyle integrates well-being characteristics and contributes to reducing the impact of unhealthy lifestyle habits with practical implications for primary care. Combining lifestyle, metabolic, and quality of life traits will facilitate personalized precision interventions and the implementation of targeted public health policies.

Background: The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain., Methods: Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals., Results: Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7-9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis ( p  < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain., Conclusions: Glu89Lys ATTRv is a TTR variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.

Objective: Calculate the efficiency of the EmERGE Pathway of Care for medically stable people living with HIV at the Hospital Clínic-IDIBAPS, Barcelona, Spain., Methods: 546 study participants were followed between 1st July 2016 and 30th October 2019 across three HIV outpatient clinics, but the virtual clinic was closed during the second year. Unit costs were calculated, linked to mean use outpatient services per patient year, one-year before and after the implementation of EmERGE. Costs were combined with primary and secondary outcomes., Results: Annual costs across HIV-outpatient services increased by 8%: €1073 (95%CI €999-€1157) to €1158 (95%CI €1084-€1238). Annual cost of ARVs was €7,557; total annual costs increased by 1% from €8430 (95%CI €8356-8514) to €8515 (95%CI €8441-8595). Annual cost for 433 participants managed in face-to-face (F2F) clinics decreased by 5% from €958 (95%CI 905-1018) to €904 (95%CI 863-945); participants transferred from virtual to F2F outpatient clinics (V2F) increased their annual cost by a factor of 2.2, from €115 (95%CI 94-139) to €251 (95%CI 219-290). No substantive changes were observed in primary and secondary outcomes., Conclusion: EmERGE Pathway is an efficient and acceptable intervention. Increases in costs were caused by internal structural changes. The cost reduction observed in F2F clinics were off-set by the transfer of participants from the virtual to the F2F clinics due to the closure of the virtual clinic during the second year of the Study. Greater efficiencies are likely to be achieved by extending the use of the Pathway to other PLHIV., (Copyright © 2020 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. Its etiology is largely unknown but increasing incidence rates observed worldwide suggest that lifestyle and environmental factors such as diet might play a role in the development of CLL. Hence, we hypothesized that the consumption of ultra-processed food and drinks (UPF) might be associated with CLL. Data from a Spanish population-based case-control study (MCC-Spain study) including 230 CLL cases (recruited within three years of diagnosis) and 1634 population-based controls were used. The usual diet during the previous year was collected through a validated food frequency questionnaire and food and drink consumption was categorized using the NOVA classification scheme. Logistic regression models adjusted for potential confounders were used. Overall, no association was reported between the consumption of UPF and CLL cases (OR per each 10% increase of the relative contribution of UPF to total dietary intake = 1.09 (95% CI: 0.94; 1.25)), independently of the Rai stage at diagnosis. However, when analyses were restricted to cases diagnosed within <1 year (incident), each 10% increment in the consumption of UPF was associated with a 22% higher odds ratio of CLL (95% CI: 1.02, 1.47) suggesting that the overall results might be affected by the inclusion of prevalent cases, who might have changed their dietary habits after cancer diagnosis. Given the low number of cases in the subgroup analyses and multiple tests performed, chance findings cannot totally be ruled out. Nonetheless, positive associations found in CLL incident cases merit further research, ideally in well-powered studies with a prospective design.

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Background: The aim of this study was to have a better understanding of the influence of the coronavirus disease 2019 (COVID-19) pandemic in people with epilepsy (PWE) and to assess whether there have been changes in seizure control during the current COVID-19 outbreak, exploring the possible causes thereof., Methods: This is an observational, retrospective study based on prospective data collection of 100 successive patients who attended an epilepsy outpatient clinic either face-to-face or telephonically during the months of the COVID-19 outbreak and national state of emergency., Results: One hundred patients were included, 52% women, mean age 42.4 years. During the COVID-19 period, 27% of the patients presented an increase of >50% of seizure frequency. An increase of stress/anxiety (odds ratios (OR): 5.78; p = 0.008) and a prior higher seizure frequency (OR: 12.4; p = 0.001) were associated with worsening of seizures. Other risk factors were exacerbation of depression, sleep deprivation, less physical activity, and history of epilepsy surgery. Three patients had status epilepticus (SE) and one a cluster of seizures. Likewise, 9% of patients improved their seizure control. Reduction in stress/anxiety (OR: 0.05; p = 0.03) and recent adjustment of antiepileptics (OR: 0.07; p = 0.01) acted as protecting factors., Conclusions: A high proportion of PWE suffered a significant worsening of their seizure control during the months of the COVID-19 pandemic. Emotional distress due to home confinement was the main factor for the change in seizure control. Promoting physical activity and adequate sleep may minimize the potential impact of the pandemic in PWE. Ensuring correct follow-up can prevent decompensation in those PWE at high risk., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT)., Objective: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers., Results: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant., Conclusions: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We aimed to study the association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) in Spain. Occupational exposure to pesticides (four insecticides, four herbicides and two fungicides) was evaluated using a job-exposure matrix for the Spanish population (MatEmESp) among 302 CLL cases and 1567 population controls in five regions of Spain, 2010-2013. Cumulative exposure scores (CES) were obtained by summing across the exposed jobs the product of prevalence, intensity and duration of exposure to each active substance. Principal components analysis (PCA) and logistic regression models adjusted for age, sex, region, education and occupational exposure to solvents were used. Around 20% of controls and 29% of cases were exposed to one or more pesticides. Compared to non-exposed, subjects in the highest tertile (3rd tertile) of CES of insecticides, herbicides, fungicides were more likely to have CLL [OR (95% CI), P-trend; 2.10 (1.38; 3.19), 0.002; 1.77 (1.12; 2.80), 0.12; and 1.67 (1.06; 2.64), 0.10, respectively). Following PCA, the first component (PC1, explaining 70% of the variation) equally led by seven active substances (the insecticide pyrethrin, all herbicides, all fungicides) was associated with a 26% higher odds of having CLL for 1-standard deviation increase in PC1 (95% CI: 1.14 to 1.40). These results confirm previous associations between CLL and exposure to pesticides and provide additional evidence by application groups and active substance. However, more research is needed to disentangle independent effects of individual active substances.

Lymphomas are a large, heterogeneous group of neoplasms with well-defined characteristics, and this heterogeneity highlights the importance of epidemiological data. Knowledge of local epidemiology is essential to optimise resources, design clinical trials, and identify minority entities. Given there are few published epidemiological data on lymphoma in Spain, the Spanish Lymphoma and Autologous Bone Marrow Transplant Group created the RELINF project. The aim of this project is to determine the frequencies and distribution of lymphoid neoplasms in Spain and to analyse survival. We developed an online platform for the prospective collection of data on newly diagnosed cases of lymphoma in Spain between January 2014 and July 2018; 11,400 patients were registered. Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) were the most frequent lymphomas in our series. Marginal B cell lymphoma frequency was higher than that reported in other studies, representing more than 11% of mature B cell lymphomas. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) was the most common subtype of T cell lymphoma, and NK/T cell lymphomas were more frequent than expected (5.4% of total). Hodgkin's lymphoma accounted for 12% of lymphoproliferative syndromes. Overall survival was greater than 90% at 2 years for indolent B cell lymphomas, and approximately 60% for DLBCL, somewhat lower than that previously reported. Survival was poor for PTCL-NOS and angioimmunoblastic T cell lymphoma, as expected; however, it was somewhat better than that in other studies for anaplastic large cell anaplastic lymphoma kinase lymphomas. This is the first prospective registry to report the frequencies, distribution, and survival of lymphomas in Spain. The frequencies and survival data we report here are globally consistent with that reported in other Western countries. These updated frequencies and survival statistics are necessary for developing appropriate management strategies for neoplasias in the Spanish population.

Introduction: Preventable risk factors for chronic lymphocytic leukemia (CLL) remain largely unknown. The aim of this study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and CLL, in the MCC-Spain case-control study., Methods: A total of 318 CLL cases and 1293 population-based controls were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on the 2018 recommendations for cancer prevention (on body fatness, physical activity, and diet) was constructed. We used logistic regression analysis adjusting for potential confounders., Results: Individuals in the highest tertile of the WCRF/AICR score had an odds ratio for CLL of 1.25 (95 % CI 0.91; 1.73) compared with individuals with low adherence (p-trend = 0.172). Each point increment in the score was associated with an OR for CLL of 1.06 (95 % CI 0.91; 1.23). Analyses by severity of disease did not show significant heterogeneity of effects., Conclusion: Overall, our results do not support an association between the WCRF/AICR score and CLL, yet we might have been limited by statistical power and study design to detect modest associations. Further research, ideally with a prospective design, long follow-up, and including additional lymphoma subtypes, is warranted to confirm the impact of composite healthy lifestyle behaviors on lymphoma risk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To assess the impact of Triepi-45-a tool that enables an episiotomy angle of 45° to be marked on the perineum at rest-on the incidence of obstetric anal sphincter injuries (OASIS) during operative vaginal delivery (OVD)., Method: A retrospective-prospective cohort study was performed among successive women who underwent OVD at Complejo Asistencial Universitario de de León, Spain, between 2011 and 2013 (preintervention cohort, n=986) and between 2014 and 2016 (intervention cohort, n=986) after implementation of an interventional programme in 2013 to improve the episiotomy angle, including use of Triepi-45, in OVD., Results: The intervention cohort had a lower incidence of OASIS than the preintervention cohort (70/986 [7.1%] vs 93/986 [9.4%]), but the difference was not significant, owing to the low use of Triepi-45 in the intervention cohort (n=375). However, the OASIS incidence was significantly lower in the Triepi-45 cohort than in the preintervention cohort (18/375 [4.8%] vs 93/986 [9.4%]; odds ratio, 0.47; 95% confidence interval, 0.26-0.86)., Conclusion: Use of Triepi-45 had a positive impact on reducing OASIS in OVD. It remains essential to raise obstetricians' awareness of the importance of the episiotomy angle and to implement the systematic use of tools to reduce the incidence of OASIS., (© 2019 International Federation of Gynecology and Obstetrics.)

Background: In recent years, there have been significant changes in the perception of valvular and vascular allograft transplants. Despite the constant evolution of the field of transplant and the involvement of multiple surgical specialties, there is not an official registry for administrative and clinical control. This study aims to design a registry of vascular and valvular allograft transplantation in Catalonia, Spain (ReVAC)., Materials and Methods: Three consecutive focal groups were designed. Focal groups established administrative, technical, and clinical requirements of ReVAC. ReVAC included patients with a transplanted cryopreserved vascular segment or cardiac valves that were distributed by Catalan tissue banks to public and private hospitals in Catalonia. Ten hospitals were involved in this study. Data were collected on 380 patients between January 1995 and November 2015., Results: The project resulted in the completion of a growing platform available online. ReVAC was divided into the following 3 levels: patient-related, surgery-related, and transplant-related data. Online access is available through the website of applications of the "Generalitat de Catalunya.", Conclusion: ReVAC has been useful for administrative and clinical control of transplants in Catalonia. Currently, data related to outcomes of arterial allografts are available, reinforcing the current guideline-supported indications, as well as opening a window for further analysis and guideline creation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Sexual assault (SA) is recognized as a public health problem of epidemic proportions. Guidelines recommend the administration of post-exposure prophylaxis (PEP) after an SA. However, few data are available about the feasibility of this strategy, and this study was conducted to assess this., Methods: We conducted a retrospective, longitudinal, observational study in SA victims attending the Hospital Clinic in Barcelona from 2006 to 2015. A total of 1695 SA victims attended the emergency room (ER), of whom 883 met the PEP criteria. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180 in the out-patient clinic. The primary endpoint was PEP completion rate at day 28. Secondary endpoints were loss to follow-up, treatment discontinuation, occurrence of adverse events (AEs) and rate of seroconversion., Results: The median age of participants was 25 years [interquartile range (IQR) 21-33 years] and 93% were female. The median interval between exposure and presentation at the ER was 13 h (IQR 6-24 h). The level of risk was appreciable in 47% (n = 466) of individuals. Of 883 patients receiving PEP, 631 lived in Catalonia. In this group, the PEP completion rate at day 28 was 29% (n = 183). The follow-up rate was 63% (n = 400) and 38% (n = 241) at days 1 and 28, respectively. Treatment discontinuation was present in 58 (15%) of 400 patients who attended at least the day 1 visit, the main reason being AEs (n = 35; 60%). AEs were reported in 226 (56%) patients, and were mainly gastrointestinal (n = 196; 49%). Only 211 (33%) patients returned for HIV testing at day 90. A single seroconversion was observed in a men who have sex with men (MSM) patient at day 120., Conclusions: Follow-up and compliance rates in SA victims were poor. In addition, > 50% of the patients experienced AEs, which were the main reason for PEP interruption. Strategies to increase follow-up testing and new better tolerated drug regimens must be investigated to address these issues., (© 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Chronic inflammation plays a role in the development of chronic lymphocytic leukaemia (CLL), and diet might modulate chronic inflammation. This study aims to evaluate the association between the dietary inflammatory index (DII ® ) and CLL. A total of 366 CLL cases and 1643 controls of the Spanish multicase-control (MCC) Spain study were included. The inflammatory potential of the diet was assessed using the energy-adjusted dietary inflammatory index (E-DII) based on 30 items from a validated semi-quantitative food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for potential confounders. Overall, a modest, non-statistically significant, positive association was observed between CLL and E-DII scores (OR for a one-unit increase in E-DII: 1.05 (CI 95%: 0.99, 1.12), p -value = 0.09 and by tertiles: OR T2vsT1 : 1.20 (CI 95%: 0.90, 1.59); OR T3vsT1 : 1.21 (CI 95%: 0.90, 1.62), p trend = 0.21). These results were independent from disease severity ( p- het: 0.70), time from diagnosis ( p- het: 0.67) and CLL treatment received ( p- het: 0.56). No interactions were detected. In conclusion, the consumption of a diet with high pro-inflammatory components was not significantly associated with CLL. Changes towards a more pro-inflammatory dietary pattern in younger generations not included here warrant future research.

Objectives: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital., Methods: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of C max /MIC, C max /MPC (mutant prevention concentration), AUC 0-48h /MIC, AUC 0-48h /MPC and %T MSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation., Results: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %T MSW that prevented enrichment of resistant mutants was <61.5%. The AUC 0-48h /MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %T MSW as a predictive parameter., Conclusion: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC 0-48h /MPC, lowest %T MSW ), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: Germline mutations in DNA damage repair (DDR) genes are identified in a significant proportion of patients with metastatic prostate cancer, but the clinical implications of these genes remain unclear. This prospective multicenter cohort study evaluated the prevalence and effect of germline DDR (gDDR) mutations on metastatic castration-resistance prostate cancer (mCRPC) outcomes., Patients and Methods: Unselected patients were enrolled at diagnosis of mCRPC and were screened for gDDR mutations in 107 genes. The primary aim was to assess the impact of ATM/BRCA1/BRCA2/ PALB2 germline mutations on cause-specific survival (CSS) from diagnosis of mCRPC. Secondary aims included the association of gDDR subgroups with response outcomes for mCRPC treatments. Combined progression-free survival from the first systemic therapy (PFS) until progression on the second systemic therapy (PFS2) was also explored., Results: We identified 68 carriers (16.2%) of 419 eligible patients, including 14 with BRCA2, eight with ATM, four with BRCA1, and none with PALB2 mutations. The study did not reach its primary end point, because the difference in CSS between ATM/BRCA1/BRCA2/PALB2 carriers and noncarriers was not statistically significant (23.3 v 33.2 months; P = .264). CSS was halved in germline BRCA2 (g BRCA2) carriers (17.4 v 33.2 months; P = .027), and g BRCA2 mutations were identified as an independent prognostic factor for CCS (hazard ratio [HR], 2.11; P = .033). Significant interactions between g BRCA2 status and treatment type (androgen signaling inhibitor v taxane therapy) were observed (CSS adjusted P = .014; PFS2 adjusted P = .005). CSS (24.0 v 17.0 months) and PFS2 (18.9 v 8.6 months) were greater in g BRCA2 carriers treated in first line with abiraterone or enzalutamide compared with taxanes. Clinical outcomes did not differ by treatment type in noncarriers., Conclusion: g BRCA2 mutations have a deleterious impact on mCRPC outcomes that may be affected by the first line of treatment used. Determination of g BRCA2 status may be of assistance for the selection of the initial treatment in mCRPC. Nonetheless, confirmatory studies are required before these results can support a change in clinical practice.

Background: Food allergy is a very frequent and increasingly common disease in children and adolescents. It affects quality of life and can even be life-threatening. Given that 10-18% of allergic/anaphylactic food reactions take place in schools, it is essential to provide school personnel with training on the management of reactions., Methods: The Allergy Unit of Hospital Universitario de Fuenlabrada, Spain, organized a conference entitled "Management of Food Allergy in Children and Adolescents in School Centers" during which teachers, cooks, cafeteria monitors, and summer-camp leaders underwent a training course. Attendees filled out a questionnaire with eight questions before and after the course to assess their self-efficacy in management of food allergy and anaphylaxis. The results were compared., Results: A total of 191 people participated (51% dining-room monitors, 24% teachers, 13% cooks, and 12% other professions). The areas in which the attendees presented the lowest confidence before receiving the course were recognition of symptoms and treatment of the reactions/anaphylaxis. The mean score for each of the eight concepts evaluated improved after the training course. This improvement was significant in the management of anaphylaxis., Conclusions: Our study demonstrates the usefulness of a self-efficacy scale in school personnel as a tool to assess the ability to manage food allergy and anaphylaxis. It can help to identify problem areas in which more specific training programs can be implemented., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P -trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings., (Copyright© 2018 Ferrata Storti Foundation.)

Introduction: Chronic Lymphocytic Leukemia (CLL/SLL) is the most common adult leukemia in Western countries. Although it is mostly an indolent disease it is still incurable and with limited knowledge in relation to its etiology. We aim to confirm and quantify established risk factors for CLL/SLL using a multi-center epidemiological population-based case-control study on CLL/SLL as well as to explore new exposures inconclusively associated with CLL/SLL METHODS: Using the framework provided by the large MCC-Spain case-control study, we explored established and suggested risk factors associated with CLL/SLL using data collected through a face-to-face interview. We estimated odds ratios (OR) and confidence intervals (CI) adjusted by basic confounders, in 1,845 controls from the general population and 560 CLL/SLL from 5 different Spanish regions., Results: Among the established risk factors, CLL/SLL cases were 3 times more likely to report first degree relatives with an hematological cancer (OR = 3.11, 95% CI 2.10 to 4.61) and nearly twice likely to have ever worked in agriculture (OR = 1.70, 95% CI = 1.34 to 2.16). New findings suggest that women with CLL/SLL were more likely to have central obesity (OR = 1.67 95% CI = 1.12 to 2.48). An inverse association was found for current alcohol consumption (p-trend<0.016) and for type II diabetes., Conclusion: We confirmed previous established risk factors for CLL/SLL. Among the new findings, further research of central obesity as preventable exposure and the treatment for type II diabetes are warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population., Methods: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay., Results: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type., Conclusions: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Background: Respiratory viral infections are a major cause of hospitalisation in infants <1 year and might cause severe symptoms in preterm infants. Our aim was to analyse admissions due to respiratory infections in moderate, late and term infants, and to identify risk factors for hospitalisation in preterm versus term., Methods: Prospective study in a cohort of moderate and late preterm, and term infants born between October/2011 and December/2012. Admissions due to respiratory infections during the first year of life were analysed and compared among moderate (32-33), late (34-36) and term infants. Sixteen respiratory viruses were detected by RT-PCR. Clinical data were collected., Results: 30 (20.9%) out of 143 preterm infants required admission for respiratory infection, versus 129 (6.9%) of 1858 term infants born in the same period (p<0.0001, OR: 3.6 CI 2.0 to 5.0). Hospitalised children had a higher prevalence of hyaline membrane disease (HMD) at birth (p<0.001, OR: 7.7 CI: 2.121 to 27.954) and needed more mechanical ventilation (p<0.001, OR: 5.7 CI: 1.813 to 18.396). Virus was identified in 25/30 (83%) preterm babies, and in 110/129 (85%) term infants. The most frequent viruses in preterm infants were RSV (76%) rhinovirus (20%). Clinical and epidemiological characteristics among term and preterm infants were similar., Conclusions: The risk of respiratory admissions during the first year of life is up to 3.6 times higher in moderate and late preterm. Once admitted, clinical features of respiratory episodes requiring hospitalisation are similar among term and preterm infants. Hyaline membrane disease and mechanical ventilation were also risk factors for respiratory admissions., (Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.)

Merkel cell polyomavirus (MCPyV) has been suspected to cause chronic lymphocytic leukaemia (CLL) but previous data are inconsistent. We measured seroreactivities of nine polyomaviruses (MCPyV, BKPyV, JCPyV, LPyV, KIPyV, WUPyV, HPyV-6, HPyV-7 and TSPyV) in 359 CLL cases and 370 controls using bead-based multiplex serology technology. We additionally tested two herpesviruses (HSV-1 and CMV). Associations between disease and viral seroreactivities were assessed using logistic regression. All human viruses showed high seroprevalences (69-99%) against structural proteins in controls but significantly lower viral seroprevalences in cases (58-94%; OR range = 0.21-0.70, P value < 0.05), except for MCPyV (OR = 0.79, 95% CI = 0.54-1.16). Lower seroreactivity levels were observed among CLL subjects, with significant differences already observed at early stages of disease, unrelated to treatment status. Seroreactivities against polyomavirus related oncoproteins were almost null. Our data suggest no association for MCPyV polyomavirus with CLL development and an unlikely association for other polyomaviruses tested.

Objective: Since the introduction of combination antiretroviral therapy (cART) patients with HIV-related diffuse large B-cell lymphoma (DLBCL) show better control of immunosuppression, which may have an impact on the characteristics and prognosis of the disease. We aimed to compare the clinical presentation and prognosis of patients with HIV-related and HIV-unrelated DLBCL treated with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) in the cART era., Methods and Design: Eighty-one HIV-infected patients included in a Spanish multicentre trial were compared with 84 HIV-uninfected patients diagnosed in a Spanish institution in the same period all treated with R-CHOP., Results: HIV-infected patients had a worse performance status, more frequent B-symptoms, and higher Ann-Arbor stages than HIV-uninfected patients, with similar frequency of extranodal involvement. The complete response (CR) rate of patients with high tumor burden was not different in HIV-infected and HIV-uninfected patients. Patients with HIV-related DLBCL showed a worse overall survival (OS) (5-year OS: 56 vs. 74%) but a similar disease-free survival (DFS) (5-year DFS: 84 vs. 73%). In the subgroup of patients with high tumor, the results regarding survival were similar to the whole series. Previous AIDS-defining illness was the strongest negative prognostic factor for OS in HIV-infected patients., Conclusion: In the cART era, HIV-related DLBCL still presents more aggressive features than HIV-unrelated DLBCL, and has a worse OS despite having a similar DFS. Prevention of HIV-related complications is essential to achieve outcomes comparable with HIV-uninfected patients with DLBCL.

Purpose: An association between neuroendocrine tumors (NETs) and second primary malignancies (SPMs) has been reported. We have examined the incidence and etiology of SPMs in patients with NETs included in the Neuroendocrine Tumor Association of Andalusia (ATNEA) Registry., Methods: Data on 111 patients were collected. Sex, age, NET site, chromogranin A levels, neuropeptide secretion and disease stage were compared between NETs with and without SPMs., Results: SPMs were present in 21 patients (18.9 %): five colorectal tumors, four non-small-cell lung cancers, three gastric cancers, two tumors in the small intestine, one hepatocarcinoma, two ovarian tumors, one breast adenocarcinoma, one hypernephroma, one bladder cancer, and one neuroblastoma. SPMs were present in 18 % of patients with a gastrointestinal NET and 22 % of those with a non-gastrointestinal NET. SPMs were found in 23 % of patients with elevated levels of serum chromogranin A, compared to 17 % of patients with normal levels, and in 22 % of patients with functional tumors, compared to 11 % of those with non-functional tumors. Finally, SPMs were observed in 24 % of patients with a local or locoregional tumor but in only 13 % of those with a metastatic tumor. No other differences between patients with and without SPMs were observed., Conclusions: The percentage of patients with SPMs in the ATNEA Registry is similar to those reported in other series. In our registry, patients with functional NETs and local/locoregional tumors have higher probability of SPMs. The low number of patients, selection bias and other etiologic factors of SPMs may have influenced our results.

Objectives: The objective of this study was to assess surveillance cultures (SC) prediction accuracy in two periods and settings of the same Department with a different microbiological epidemiology (high and low prevalence of multi-drug resistant microorganisms (MDRM))., Methods: Prospective and observational study. SC were obtained twice a week in consecutive mechanically ventilated patients. Patients fulfilling VAP criteria were analyzed., Results: 440 patients were followed up, 71 patients had VAP (50 in period I and 21 in period II). MDRM causing VAP were more prevalent in the first period (48% vs. 19%; p = 0.033). The rate of empirical appropriate treatment in period I was lower than in period II (52% vs.76%; p = 0.031). SC prediction accuracy was similar in the two periods (80% vs. 81%; p = 0.744). However, if antibiotic treatment had been guided by SC, the percentage of appropriate treatment would have increased by 28% in the first period but only by 5% in the second; p = 0.024., Conclusions: SC were able to predict VAP etiology in 80% of cases regardless the prevalence of MDRM. However, the potential benefit of SC in terms of appropriate empirical treatment could be only observed when MDRM were prevalent., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare the effectiveness of proprioceptive neuromuscular facilitation combined with exercise, classic stretching physiotherapy intervention, and educational intervention at improving patient function and pain in patients with patellofemoral pain syndrome., Design: Randomized, controlled, blind trial over four months., Setting: Urban population, Spain., Participants: Patients undergoing primary care for retropatellar pain., Intervention: Subjects were allocated on three different treatment options: a proprioceptive neuromuscular facilitation and aerobic exercise group, a classic stretching group, and a control treatment were applied over four months under the supervision of a physiotherapist., Main Outcome: Knee Society Score, pain reported (Visual analogue scale) and knee range of motion. Assessments were completed at baseline and after four months., Results: 74 patients were enrolled in the study and distributed between groups. Both the proprioceptive neuromuscular facilitation and classic stretching group showed significant changes in all variables after four months intervention (p < 0.001). The difference in mean Kujala knee score changes between groups (classic stretching group vs. proprioceptive neuromuscular facilitation group vs. control group) at four months was -24.05 (95% confidence interval (CI) -30.19, -17.90), p ≤ 0.001; vs. -39.03 (95% confidence interval (CI) -42.5, -35.5), p ≤ 0.001; vs. -0.238 (95% confidence interval (CI) -1.2, 0.726), p = 0.621, respectively., Conclusions: A proprioceptive neuromuscular facilitation intervention protocol combined with aerobic exercise showed a better outcome than a classic stretching protocol after four months.

Background: Merkel cell polyomavirus (MCV) has been identified as the cause of Merkel cell carcinoma. The increased incidence of chronic lymphocytic leukemia in Merkel cell cancer cohorts and the lymphotropic properties of the virus suggest a possible viral association with lymphomagenesis. To investigate this potential role, we explored seroreactivity against MCV VP1 capsids within the Epilymph case-control study in Spain., Methods: Serum samples from 468 incident lymphomas, categorized into up to 11 entities, and 522 controls frequency matched by age, sex, and recruitment center were tested for MCV antibodies by enzyme immunoassay using Virus-Like-Particles. Adjusted multinomial logistic regression was used to estimate the OR and 95% confidence interval (CI) associated to MCV seroprevalence. Immunosuppressed subjects were excluded., Results: MCV seroprevalence was 82% in controls and 85% in lymphoma cases. Among 11 lymphoma categories, MCV seropositivity was significantly higher in diffuse large B-cell lymphomas (DLBCL; 96.4%; OR = 6.1, 95%CI = 1.9-19.8), as compared with controls. MCV prevalences were also higher in follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and mature T-cell lymphoma but differences did not reach statistical significance. Lower prevalences were observed for multiple myeloma and other B-cell lymphoma. Exclusion of samples collected after start of treatment did not change the results. In a subset analysis, no significant association was observed between BKV and JCV seroprevalence and DLBCL., Conclusion: The association observed between serologic evidence of MCV exposure and DLBCL warrants further research., Impact: MCV might be involved in the pathway of DLBCL and other lymphomas., (©2012 AACR)

Objective: Biliary strictures are the most common biliary tract complication after liver transplantation. There are scarce data on the results of hepaticojejunostomy (HJ) in the management of biliary complications after orthotopic liver transplantation (OLT). Thus, the role of surgery in this setting remains to be established. The aim of this study was to evaluate the results of surgical treatment of patients with biliary complications at our institution., Patients and Methods: We reviewed 1000 consecutive liver transplantations performed at our institution from 1984 to 2007. We used a prospectively recorded database to identify patients who underwent HJ to treat any biliary tract complication., Results: Overall, 62 patients (6.2%) underwent HJ, 40 for an anastomotic and 7 for a non-anastomotic stricture as well as 15 for biliary leaks. Postoperative morbidity was 16%, and postoperative mortality 1.6%. There were 7 cases of anastomotic stenosis (11.3%). Four patients (5%) required retransplantation., Conclusions: HJ is a safe procedure to manage biliary complications after OLT. It may be the first treatment choice especially for cases with anastomotic strictures., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The implantable cardioverter-defibrillator (ICD) electrogram (EG) is a documentation of ventricular tachycardia. We prospectively analyzed EGs from ICD electrodes located at the right ventricle apex to establish (1) ability to regionalize origin of left ventricle (LV) impulses, and (2) spatial resolution to distinguish between paced sites., Methods and Results: LV electro-anatomic maps were generated in 15 patients. ICD-EGs were recorded during pacing from 22 ± 10 LV sites. Voltage of far-field EG deflections (initial, peak, final) and time intervals between far-field and bipolar EGs were measured. Blinded visual analysis was used for spatial resolution. Initial deflections were more negative and initial/peak ratios were larger for lateral versus septal and superior versus inferior sites. Time intervals were shorter for apical versus basal and septal versus lateral sites. Best predictive cutoff values were voltage of initial deflection <-1.24 mV, and initial/peak ratio >0.45 for a lateral site, voltage of final deflection <-0.30 for an inferior site, and time interval <80 milliseconds for an apical site. In a subsequent group of 9 patients, these values predicted correctly paced site location in 54-75% and tachycardia exit site in 60-100%. Recognition of paced sites as different by EG inspection was 91% accurate. Sensitivity increased with distance (0.96 if ≥ 2 cm vs 0.84 if < 2 cm, P < 0.001) and with presence of low-voltage tissue between sites (0.94 vs 0.88, P < 0.001)., Conclusions: Standard ICD-EG analysis can help regionalize LV sites of impulse formation. It can accurately distinguish between 2 sites of impulse formation if they are ≥2 cm apart., (© 2011 Wiley Periodicals, Inc.)

Uterine sarcomas are rare and the clinical diagnosis of sarcoma is difficult. Diagnostic and surgical hysteroscopy is a minimally invasive outpatient procedure that makes an accurate diagnosis of malignant intrauterine pathology and could play a role in the diagnosis of the uterine sarcomas. Uterine sarcomas diagnosed at the Department of Gynecology of Sant Joan University Hospital by hysteroscopy between January 2004 and August 2010 are described. In this period 2,441 hysteroscopies were performed; a total of 67 adenocarcinomas of the endometrium and five sarcomas were diagnosed by hysteroscopy. The data are presented with a review of the literature, focusing on the diagnostic value of hysteroscopy in these tumors.

We describe three positive influenza AH1N1 cases in a neonatal unit during the influenza pandemic in Spain. One term baby presented with an upper respiratory tract infection, another preterm infant with an apnea episode following nosocomial infection, and thirdly, a term infant of a mother with influenza AH1N1 had severe respiratory distress and pneumothoraces needing high-frequency ventilation., (Copyright © 2011 S. Karger AG, Basel.)

We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.

Background: Infection by human papillomavirus (HPV) is the main cause of and a necessary factor for cervical cancer. There are more than 100 known HPV genotypes, although HPV genotypes do not all have the same risk of inducing cervical cancer. The main aim of this study is to know the distribution of different types of HPV in women attending a colposcopy clinic for cervical dysplasia., Methods: We prospectively identified and enrolled a cohort of women followed for cervical dysplasia who were referred to the colposcopy clinic of University Hospital Sant Joan de Déu in Barcelona, Spain, from April 2003 to April 2007. Two cervical scrape samples from each patient were collected for routine cytology and for identification of HPV DNA. During the study period, 2 techniques (Line Probe assay and microarray assay) were used consecutively., Findings: HPV DNA was detected in 68% of patients (338 of 496 women) with statistically significant differences in positive results according to the cytologic category. Overall, the type distribution showed a predominance of genotype HPV-16 (27% of the total patients) followed by HPV-53 (9.4%), HPV-51 (8%), and HPV-51 (8%). Multiple genotype detection was observed in 35.5% of the patients with HPV infection. HPV-16 was mainly associated with the probable high-risk genotypes: HPV-53 and HPV-66., Conclusion: The higher prevalence of high-risk nonvaccine genotypes should be considered to increase vaccine efficiency.

Autosomal dominant PEO is associated with mutations in a number of nuclear genes affecting the intergenomic communication with mitochondrial DNA. We report a Spanish family showing a mild phenotype characterized by autosomal dominant ocular myopathy and morphological signs of mitochondrial dysfunction, that harboured a novel c.1071G>C (p.R357P) mutation in the hot-spot linker region of the twinkle protein.

Purpose of Investigation: To determine the prevalence of human papillomavirus (HPV) using polymerase chain reaction (PCR) in women with abnormal cytology results., Methods: A prospective study of 215 women with abnormal cytology results referred consecutively to the cervical pathology clinic was carried out. A second cervical cytology using the Bethesda System was performed on all the patients to confirm the initial diagnosis, as well as to test for the presence of HPV by PCR and a colposcopy and punch biopsy in cases presenting with an abnormal pattern on colposcopy. The sensivitiy, specificity, and positive and negative predictive value (PPV and NPV) were calculated using 2 x 2 tables., Results: The women aged 35 years or younger presented a higher percentage of HPV infection (85.6%) than the women over 35 years of age (54%). The highest percentage of women with a positive result for HPV was found in those with a cytological high-grade squamous intraepithelial lesion (HSIL) (85.5%), as compared with 47.4% of the women with a cytological low-grade squamous intraepithelial lesion (LSIL). HPV infection has a high negative predictive value (93.2% of cases) and a high sensitivity (93.5%) for the detection of HSIL by biopsy, although the specificity and positive predictive value were low, 51.5% and 52.1%, respectively., Conclusion: Patients with cytological HSIL have a high prevalence of HPV infection.

Background: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use., Objectives: This document examines the characteristics and possibilities of treatment administered once daily., Methods: Consensus of 248 Spanish experts in the field., Results: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy., Conclusions: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain., (Copyright 2003 Wiley-Liss, Inc.)

The purpose of this nonrandomized case-review study was to compare the outcome of stripping and CHIVA for treatment of varicose veins in the lower extremities in our department. Outcome was evaluated by independent physicians. A total of 85 patients underwent saphenous vein stripping in association with phlebectomy and 90 patients underwent CHIVA cure. The duration of follow-up was 3 years. Study criteria were (1) presence of varicose veins as a cause of failure (1.1% in the CHIVA group vs. 15.3% in the stripping group), (2) appearance of telangiectasia (8.9% in the CHIVA group vs. 65.9% in the stripping group), (3) patient dissatisfaction rate (3.3% in the CHIVA group vs. 16.5% in the stripping group), (4) postoperative symptoms as a cause of failure (1.1% in the CHIVA group vs. 21.2% in the stripping group), and (5) saphenous nerve injury (1 patient in the CHIVA group vs. 16 in the stripping group). Differences between all five criteria were significantly in favor of the CHIVA group as compared to saphenous vein stripping with phlebectomy. Clinical results at 3 years are better for patients treated with CHIVA than stripping with regard to presence of varicose veins, clinical symptoms, presence of telangiectasia, cosmetic satisfaction, and neurologic complications. Data in our series of CHIVA treatments are comparable to those reported in the literature and better than those described in three series of stripping procedures with 3-year follow-up. A prospective randomized study is now underway to confirm these findings.

Auditory exostoses are bone anomalies located in the external auditory canal. The bulk of clinical observations and some experimental data support the idea that their development depends on prolonged exposure to cold water. This study was performed in order to analyze the prevalence of auditory exostoses among the prehispanic population of Gran Canaria, comparing it between men and women and between individuals buried in coastal regions and central highlands. We analyzed 323 crania, 41 of which showed auditory exostoses. Marked differences in prevalence were observed between the individuals buried in the central highlands (0.88%) and those buried in coastal regions (40.21%). Among the latter, the prevalence was similar in men (41.67%) and in women (38.89%). These data support the hypothesis that individuals buried in coastal regions performed economic activities related to exploitation of marine resources, whereas those living in the central highlands did not; however, diachronic variation cannot be excluded., (Copyright 2000 Wiley-Liss, Inc.)

We have determined bone strontium (Sr), barium (Ba), calcium (Ca), and zinc (Zn) content in 24 samples belonging to adult individuals who died toward the end of the 18th century and were interred in a church's floor on the island of Tenerife, comparing the results with those obtained in 14 prehistoric samples of the same island and also with those of 7 modern controls. No differences were observed between the two ancient groups, which showed higher bone strontium and barium than the modern sample, and a slightly lower Ba/Sr ratio, thus pointing to consumption of marine sources.

The present study has been performed in order to determine concentrations of lead in the bone of 14 individuals who were interred towards the beginning of the 18th century at the church 'La Concepción' (Santa Cruz de Tenerife) of 15 Pre-Hispanic individuals of Tenerife and a modern sample for Tenerife, composed of 25 individuals. We have observed higher bone lead values in the modern population than in the ancient one (P = 0.0022), although Pre-Hispanic individuals and those of the 18th century showed similar bone lead values.

Data on the GM and KM haplotypes and RFLPs in the immunoglobulin IGHG loci are reported intending to evaluate the genetic contribution of the different populations (Europeans and Africans) who settled Tenerife Island. The GM and KM allotypic systems reveal an estimated European genetic admixture of 88%. The only possible African contribution is the presence of the GM*1,17;...;5* haplotype (2.5%), but no other traces of Black African characteristic haplotypes are found. Although new RFLP haplotypes are described, DNA variation is similar to that reported in Caucasoids with a marked absence of restriction fragments characteristic of Black Africans.

Data on six protein polymorphisms (19 alleles) from the human population of Tenerife are presented and discussed along with other classical markers in relation to the origin of the Canarians. Genetic influences from three population groups were considered: the Iberians, and the Berbers and non-Berbers (Arabs) from north Africa. The systems examined show the Tenerife population lies within the limits of variation described for various Iberian groups, with a slight tendency towards the characteristics of north African populations. When blood groups, red cell enzymes and serum protein data were considered, the similarity of the Canary population to Iberians seems strengthened (70% estimated contribution of Iberian peninsula genes to the present-day Canarian pool), while some relation with north African groups is shown. Genetic distances between Canarians and Arabs and Canarians and Berbers are lower than those between the two north African groups, indicating a relative and comparable contribution of each to the present-day gene pool of the Canarian population. The Arab contribution could be attributable to the slaves who were introduced to these islands after the conquest in the 15th century, while the Berber contribution could be the remnants of the extinct aboriginal peoples of the islands (Guanches) or a more recent immigration due to slavery. Genetic data do not allow us to distinguish between these two possibilities.

We have study oligodontia in a sample of Andalucias children. The population was between five and twelve years old. The authors wished to determine the prevalence of Oligodontia excluding third molars (the prevalence was higher than other spanish studies about the same subject). The mandibular second premolar was the most frequently absent tooth.