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A variety of strategies have been designed for sequence-based HLA typing (SBT) and for the isolation of new human leucocyte antigen ( HLA) alleles, but unambiguous characterization of complete genomic sequences remains a challenge. We recently reported a simple method for the group-specific amplification ( GSA) and sequencing of a full-length C*04 genomic sequence in isolation from the accompanying allele. Here we build on this strategy and present homologous methods that enable the isolation of HLA-C alleles belonging to another two allele groups. Using this approach, which can be applied to sequence-based typing in some clinical settings, we have successfully characterized three novel HLA-C alleles ( C*04:128, C*07:01:01:02, and C*08:62). [ABSTRACT FROM AUTHOR]

Abstract Background Infection is a major complication of cerebrospinal fluid shunting procedures. The present report assesses the efficacy of such catheters in both shunts and external ventricular drains (EVDs) against infection and particularly against Staphylococcus spp. infection. Methods All shunt and EVD procedures performed by means of antibiotic-impregnated catheters (AICs) and non-AICs during the period of study were registered. In cases of shunt procedures, a minimal follow-up of 90 days was considered, as well as de novo insertion and catheter revisions. Single valve revisions were not included. In cases of EVD procedures, those catheters removed before the fifth post-insertion day were not included. A total of 119 cerebrospinal fluid shunting procedures performed with AICs were studied in comparison with 112 procedures performed by means of non-AICs. Results Antibiotic-impregnated catheters were associated with a significant decrease in both overall and staphylococcal infection (p = 0.030 and p = 0.045, respectively). The number needed to treat for AICs was 8 to prevent one infection and 14 to prevent one staphylococcal infection. When comparing with shunts, the use of EVDs was associated with a 37-fold increased likelihood of infection. Conclusions Antibiotic-impregnated catheters are a safe and helpful tool to reduce CSF shunting device-related infections.

Introduction and Objectives: Our aim was to describe the contemporary epidemiological profile of infective endocarditis (IE) in Spain, and to evaluate variations in IE incidence, characteristics, and outcomes among the different Spanish regions (autonomous communities [AC])., Methods: We conducted a retrospective, population-based study, using data obtained from national in-patient hospital activity of all patients discharged with a diagnosis of IE from hospitals included in the Spanish National Health System, from January 2016 to December 2019. Differences in the IE profile between the 17 Spanish AC were analyzed., Results: A total of 9008 hospitalization episodes were identified during the study period. Standardized incidence of IE was 5.77 (95%CI, 5.12-6.41) cases per 100 000 population. Regarding predisposing conditions, 26.8% of episodes occurred in prosthetic valve carriers, 36.8% had some kind of valve heart disease, and 10.6% had a cardiac implantable electronic device. Significant differences were found between AC in terms of incidence, predisposing conditions, and microbiological profile. Cardiac surgery was performed in 19.3% of episodes in the total cohort, and in 33.4% of the episodes treated in high-volume referral centers, with wide variations among AC. Overall in-hospital mortality was 27.2%. Risk-adjusted mortality rates also varied significantly among regions., Conclusions: We found wide heterogeneity among Spanish AC in terms of incidence rates and the clinical and microbiological characteristics of IE episodes. The proportion of patients undergoing surgery was low and in-hospital mortality rates were high, with wide differences among regions. The development of regional networks with referral centers for IE could facilitate early surgery and improve outcomes., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: The aim of this study was to analyze whether nonelective admissions in patients with heart failure (HF) on nonworking days (NWD) are associated with higher in-hospital mortality., Methods: We conducted a retrospective (2018-2019) observational study of episodes of nonelective admissions in patients aged 18 years and older discharged with a principal diagnosis of HF in acute general hospitals of the Spanish National Health System. NWD at admission were defined as Fridays after 14:00hours, Saturdays, Sundays, and national and regional holidays. In-hospital mortality was analyzed with logistic regression models. The length of NWD was considered as an independent continuous variable. Propensity score matching was used as a sensitivity analysis., Results: We selected 235 281 episodes of nonelective HF admissions. When the NWD periods were included in the in-hospital mortality model, the increases in in-hospital mortality compared with weekday admission were as follows: 1 NWD day (OR, 1.11; 95%CI, 1.07-1.16); 2 days (OR, 1.13; 95%CI, 1.09-1.17); 3 (OR, 1.16; 95%CI, 1.05-1.27); and ≥4 days (OR, 1.20; 95%CI, 1.09-1.32). There was a statistically significant association between a linear increase in NWD and higher risk-adjusted in-hospital mortality (chi-square trend P=.0002). After propensity score matching, patients with HF admitted on NWD had higher in-hospital mortality than those admitted on weekdays (OR, 1.11; average treatment effect, 12.2% vs 11.1%; P<.001)., Conclusions: We found an association between admissions for decompensated HF on an NWD and higher in-hospital mortality. The excess mortality is likely not explained by differences in severity. In this study, the "weekend effect" tended to increase as the NWD period became longer., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pérez-Blanco, Acevedo, Padilla, Gómez, Zapata, Barber, Martínez, Calleja, Rivero, Fernández, Velasco, Flores, Quindós, Rodríguez, Virgós, Robles, Nebra, Moya, Trenado, García, Vallejo, Herrero, García, Rodríguez, García, Lara, Lage, Gil, Guerrero, Meilán, Del Prado, Fernández, Coll and Domínguez-Gil.)

Introduction and Objectives: The aim of this study was to analyze the clinical profile, management, and prognosis of ST segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) requiring interhospital transfer, as well as the prognostic impact of structural variables of the treating centers in this setting., Methods: This study included patients with STEMI-CS treated at revascularization-capable centers from 2016 to 2020. The patients were divided into the following groups: group A: patients attended throughout their admission at hospitals with interventional cardiology without cardiac surgery; group B: patients treated at hospitals with interventional cardiology and cardiac surgery; and group C: patients transferred to centers with interventional cardiology and cardiac surgery. We analyzed the association between the volume of STEMI-CS cases treated, the availability of cardiac intensive care units (CICU), and heart transplant with hospital mortality., Results: A total of 4189 episodes were included: 1389 (33.2%) from group A, 2627 from group B (62.7%), and 173 from group C (4.1%). Transferred patients were younger, had a higher cardiovascular risk, and more commonly underwent revascularization, mechanical circulatory support, and heart transplant during hospitalization (P<.001). The crude mortality rate was lower in transferred patients (46.2% vs 60.3% in group A and 54.4% in group B, (P<.001)). Lower mortality was associated with a higher volume of care and CICU availability (OR, 0.75, P=.009; and 0.80, P=.047)., Conclusions: The proportion of transfers in patients with STEMI-CS in our setting is low. Transferred patients were younger and underwent more invasive procedures. Mortality was lower among patients transferred to centers with a higher volume of STEMI-CS cases and CICU., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Heart failure (HF) is a major health problem in Western countries, and a leading cause of hospitalizations and death. There is a scarcity of data on the influence of sex on HF outcomes in elderly patients. The aim of the present study was to analyze differences between men and women in clinical characteristics, in-hospital mortality, 30-day HF readmission rates, cardiovascular mortality and HF readmission rates at 1 year after discharge in patients older than 75 years hospitalized for HF in Spain., Methods: Retrospective analysis of patients discharged with a main diagnosis of HF from all Spanish public hospitals between 2016 and 2019. Patients aged 75 years or older were selected, and a comparison was made between male and female patients., Results: From 2016 to 2019, a total of 354,786 episodes of HF in this age subgroup were identified, 59.2% being women. The overall mean age was 85.2 ± 5.4 years, being higher in women (85.9 ± 5.5 vs. 84.2 ± 5.3 years, p < 0.001). Risk-adjusted in-hospital mortality was lower in women (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.92-0.97; p < 0.001). Female sex also showed a protective effect for 30-day readmissions, with an OR of 1.06 (95% CI: 1.04-1.09; p < 0.001). One-year cardiovascular mortality (24.1% vs. 25.0%; p < 0.001) and one-year HF readmission rates (30.8% vs. 31.6%; p = 0.001) were lower in women., Conclusions: Almost 60% of hospital admissions for HF in people aged 75 years or older between 2016 and 2019 in Spain were female patients. Female sex seems to play a protective role on in-hospital mortality and the rate of admissions and mortality at 1 year after discharge.

Background: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction. Revascularization in SCAD remains very challenging and therefore is not recommended as the initial management strategy in stable SCAD without high-risk features., Objectives: The aim of this study was to compare in-hospital mortality and 30-day readmission rates between patients with SCAD with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI) and patients with STEMI without SCAD undergoing PPCI., Methods: This study was conducted using the administrative minimum dataset of the Spanish National Health System (2016-2020). Risk-standardized in-hospital mortality ratios and readmission ratios were calculated, and results were adjusted using propensity score (PS) analyses., Results: A total of 65,957 episodes of PPCI were identified after exclusions. The crude in-hospital mortality rate was 4.8%. Of these, 315 (0.5%) were SCAD PPCI and 65,642 were non-SCAD PPCI. SCAD PPCI patients were younger and more frequently women than non-SCAD PPCI patients. Crude mortality (5.7% vs 4.8%), risk-standardized in-hospital mortality ratio (5.3% vs 5.3%), and PS-adjusted (315 pairs) mortality (5.7% vs 5.7%) were similar in SCAD PPCI and non-SCAD PPCI patients. In addition, crude (3% vs 3.3%) and PS-adjusted (297 pairs) 30-day readmission rates (3% vs 4%) were also similar in both groups., Conclusions: PPCI, when indicated in patients with STEMI and SCAD, has similar in-hospital mortality and 30-day readmission rates compared with PPCI for atherothrombotic STEMI. These findings support the value of PPCI in selected patients with SCAD., Competing Interests: Funding Support and Author Disclosures This work has received an unconditional grant from MENARIN to the Spanish Society of Cardiology (RECALCAR project). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: Concomitant coronary artery disease (CAD) is prevalent among aortic stenosis patients; however the optimal therapeutic strategy remains debated. We investigated periprocedural outcomes among patients undergoing transcatheter aortic valve implantation with percutaneous coronary intervention (TAVI/PCI) vs surgical aortic valve replacement with coronary artery bypass grafting (SAVR/CABG) for aortic stenosis with CAD., Methods: Using discharge data from the Spanish National Health System, we identified 6194 patients (5217 SAVR/CABG and 977 TAVI/PCI) between 2016 and 2019. Propensity score matching was adjusted for baseline characteristics. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were in-hospital complications and 30-day cardiovascular readmission., Results: Matching resulted in 774 pairs. In-hospital all-cause mortality was more common in the SAVR/CABG group (3.4% vs 9.4%, P <.001) as was periprocedural stroke (0.9% vs 2.2%; P=.004), acute kidney injury (4.3% vs 16.0%, P <.001), blood transfusion (9.6% vs 21.1%, P <.001), and hospital-acquired pneumonia (0.1% vs 1.7%, P=.001). Permanent pacemaker implantation was higher for matched TAVI/PCI (12.0% vs 5.7%, P <.001). Lower volume centers (< 130 procedures/y) had higher in-hospital all-cause mortality for both procedures: TAVI/PCI (3.6% vs 2.9%, P <.001) and SAVR/CABG (8.3 vs 6.8%, P <.001). Thirty-day cardiovascular readmission did not differ between groups., Conclusions: In this large contemporary nationwide study, percutaneous management of aortic stenosis and CAD with TAVI/PCI had lower in-hospital mortality and morbidity than surgical intervention. Higher volume centers had less in-hospital mortality in both groups. Dedicated national high-volume heart centers warrant further investigation., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Heart failure (HF) is one of the leading causes of hospitalization and death in elderly patients. However, there is limited evidence on readmission and mortality 1-year after discharge for HF., Methods: Retrospective analysis of the Minimum Basic Data Set, including HF episodes, discharged from Spanish hospitals between 2016 and 2018 in ≥ 75 years. We calculated: (a) the rate of readmissions due to circulatory system diseases (CSD) 365 days after index episode; (b) in-hospital mortality in readmissions; and (c) predictors of mortality and readmission., Results: We included 178,523 patients (59.2% women) aged 85.1 ± 5.5 years. The most frequent comorbidities were arrhythmias (56.0%) and renal failure (39.5%). During the follow-up, 48,932 patients (27.4%) had at least one readmission for CSD and a crude rate of 40.2%, the most frequent one HF (52.8%). The median between the date of readmission and discharge from the last admission was 70 days [IQI 24; 171] for the first readmission. The most relevant predictors of the number of readmissions were valvular heart disease and myocardial ischemia. During the readmissions, 26,757 patients (79.1%) died, representing a cumulative in-hospital mortality of 47,945 (26.9%). The factors in the index episode predictors of mortality during readmissions were cardio-respiratory failure and stroke. The number of readmissions was a risk factor for in-hospital mortality (OR 1.13; 95% CI 1.11-1.14)., Conclusions: The readmission rate for CSD 1-year after the index episode of HF in patients ≥ 75 years was 28.4%. The cumulative in-hospital mortality rate during the readmissions was 26.9%, and the number of rehospitalizations was identified as one of the main predictors of mortality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: RECALSEEN project aims to analyze the structure, activity, and outcomes of the departments of endocrinology and nutrition (S-U&#95;EyN) of the Spanish National Health System (SNHS). Based on the results obtained, the challenges for the specialty are analyzed and proposals for improvement policies are made. In this paper 2021 survey data and activity data from the 2007-2019 from the Minimum Basic Data Set (MBDS) are presented., Material and Methods: Cross-sectional descriptive study of the S-U&#95;EyN of acute general hospitals of the NHS in 2020. Data were obtained through: 1. an "ad hoc" survey answered by the S-U&#95;EyN' consultants; and 2. analysing the acute general hospital discharges from S-U&#95;EyN and discharges with endocrine-metabolic comorbidities registered in the minimum basis data set (MBDS) of the SNHS., Results: 112 responses from S-U&#95;EyN were obtained from a total of 154 general acute hospitals of the NHS (73%). The 2021 S-U&#95;EyN sample includes 24 more centers than in 2017. 54% of the S-U&#95;EyN were endocrinology departments. The median number of endocrinologists per S-U&#95;EyN was 7. The estimated rate of endocrinologists was 2.5 per 100,000 inhabitants. S-U&#95;EyN showed a high level of collaboration with primary care teams and other hospital units. Use of telemedicine by S-U&#95;EyN experienced a high increase in 2020. Notable differences in resources and activity have been found between hospitals and Autonomous Communities. There was a wide margin for improvement in quality management., Conclusions: RECALSEEN is a useful project for the analysis of S-U&#95;EyN. The remarkable variability found in the indicators of structure, activity and management probably indicates a wide margin for improvement., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Cardiogenic shock (CS) is associated with high mortality. The purpose of this study was to assess the impact of hospital structure-related variables on mortality in patients with CS treated at percutaneous and surgical revascularization capable centres (psRCC) from a large nationwide registry., Methods and Results: Retrospective observational study including consecutive patients with main or secondary diagnosis of CS and ST elevation myocardial infarction (STEMI). Patients discharged from Spanish National Healthcare System psRCC were included (2016-20). The association between the volume of CS cases attended by each centre, availability of intensive cardiac care unit (ICCU) and heart transplantation (HT) programmes, and in-hospital mortality was assessed by multilevel logistic regression models. The study population consisted of 3074 CS-STEMI episodes, of whom 1759 (57.2%) occurred in 26 centres with ICCU. A total of 17/44 hospitals (38.6%) were high-volume centres, and 19/44 (43%) centres had HT programmes availability. Treatment at HT centres was not associated with a lower mortality (P = 0.121). Both high volume of cases and ICCU showed a trend to an association with lower mortality in the adjusted model [odds ratio (OR): 0.87 and 0.88, respectively]. The interaction between both variables was significantly protective (OR 0.72; P = 0.024). After propensity score matching, mortality was lower in high-volume hospitals with ICCU (OR 0.79; P = 0.007)., Conclusion: Most CS-STEMI patients were attended at psRCC with high volume of cases and ICCU available. The combination of high volume and ICCU availability showed the lowest mortality. These data should be taken into account when designing regional networks for CS management., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction and Objectives: The RECALCAR project (Resources and Quality in Cardiology), an initiative of the Spanish Society of Cardiology, aims to standardize information to generate evidence on cardiovascular health outcomes. The objective of this study was to analyze trends in the resources and activity of cardiology units and/or services and to identify the results of cardiovascular care during the last decade in Spain., Methods: The study was based on the 2 annual data sources of the RECALCAR project: a survey on resources and activity of cardiology units and/or services (2011-2020) and the minimum data set of the National Health System (2011-2019), referring to heart failure (HF), STEMI, and non-STEMI., Results: The survey included 70% of cardiology units and/or services in Spain. The number of hospital beds and length of stay decreased, while there was a notable increase in the number of cardiac imaging studies and percutaneous therapeutic procedures performed. Age- and sex-adjusted admissions for HF tended to decrease, despite an increase in mortality and the percentage of readmissions. In contrast, the trend in mortality and readmissions was highly favorable in STEMI; in non-STEMI, although positive, the trend was less marked., Conclusions: The information provided by the RECALCAR project shows a favorable trend in the last decade in resources, activity and results of certain cardiovascular processes and constitutes an essential source for future improvements and decision-making in health policy., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Coronary revascularization in patients with spontaneous coronary artery dissection (SCAD) is challenging. Indications and results of percutaneous coronary interventions (PCI) in SCAD patients are not well established., Aim: To assess indications and results of PCI in SCAD., Methods: The minimum basic data set of the Spanish National Health System (years 2016-2019) was used to identify 804 episodes of acute myocardial infarction (AMI) and SCAD, with a crude in-hospital mortality rate of 3%. Of these, 368 (46.8%) patients were revascularized with PCI during admission whereas 436 (54.2%) were managed conservatively., Results: Revascularization and in-hospital mortality rates both declined over the study period (p for trend both < 0.05). SCAD patients treated with PCI were older, more frequently male, and had higher frequency of diabetes, ST-segment elevation AMI and cardiogenic shock, compared to patients managed conservatively. The crude in-hospital mortality rate was higher in patients treated with PCI (4.9% vs. 1.4%; p = 0.004). However, after adjusting by propensity score (223 pairs) the in-hospital mortality rate was similar in the two groups (Adj OR: 1.21; 95%CI: 0.30-1.57; p = 0.76). Readmissions at 30-days were higher in patients managed conservatively (7.1 vs. 1.6%, p < 0.001) and this difference was maintained after propensity score adjustment (Adj average treatment effect: 2% vs. 12.2%; OR: 0.15; 95%CI: 0.04-0.45; p < 0.001)., Conclusion: Revascularization is frequently used in unselected patients with AMI and SCAD but its use is declining. Patients with SCAD treated with PCI have a higher in-hospital mortality but this appears to be explained by their adverse baseline clinical characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alfonso, Fernández-Pérez, del Prado, García-Guimaraes, Bernal, Bastante, del Val, García-Márquez and Elola.)

Introduction and Objectives: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI). We sought to compare the results on in-hospital mortality and 30-day readmission rates among patients with AMI-SCAD vs AMI due to other causes (AMI-non-SCAD)., Methods: Risk-standardized in-hospital mortality (rIMR) and risk-standardized 30-day readmission ratios (rRAR) were calculated using the minimum dataset of the Spanish National Health System (2016-2019)., Results: A total of 806 episodes of AMI-SCAD were compared with 119 425 episodes of AMI-non-SCAD. Patients with AMI-SCAD were younger and more frequently female than those with AMI-non-SCAD. Crude in-hospital mortality was lower (3% vs 7.6%; P<.001) and rIMR higher (7.6±1.7% vs 7.4±1.7%; P=.019) in AMI-SCAD. However, after propensity score adjustment (806 pairs), the mortality rate was similar in the 2 groups (AdjOR, 1.15; 95%CI, 0.61-2,2; P=.653). Crude 30-day readmission rates were also similar in the 2 groups (4.6% vs 5%, P=.67) whereas rRAR were lower (4.7±1% vs 4.8%±1%; P=.015) in patients with AMI-SCAD. Again, after propensity score adjustment (715 pairs) readmission rates were similar in the 2 groups (AdjOR, 1.14; 95%CI, 0.67-1.98; P=.603)., Conclusions: In-hospital mortality and readmission rates are similar in patients with AMI-SCAD and AMI-non-SCAD when adjusted for the differences in baseline characteristics. These findings underscore the need to optimize the management, treatment, and clinical follow-up of patients with SCAD., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). Objective: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. Methods: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. Results: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54-0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. Conclusions: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient., Competing Interests: Outside of submitted work: MF-R reported grants and personal fees from Aimmune Therapeutics and Diater, personal fees from DBV, Allergy Therapeutics, GSK, HAL Allergy, Novartis, ThermoFisher Scientific, and SPRIM. BB-W reported personal fees from ThermoFisher Scientific. FB reported personal fees from Aimmune; grants from Stallergènes Greer, Chiesi, Mundipharma, Novartis, and Regeneron; and board membership for DVB, Stallergènes Greer, Novartis, ALK, Mundipharma, Boehringer, AstraZeneca, Medapharma, and Boston Scientific. JL was an employee of ThermoFisher Scientific. NP reported personal fees from Novartis, Nutricia, HAL Allergy BV, Menarine/Faes Farma, Sanofi, Mylan/Meda, Biomay, AstraZeneca, GSK, MSD, ASIT Biotech, Boehringer Ingelheim; and grants from Gerolymatos International SA, and Capricare. SV reported personal fees from Ärzteverband Deutscher Allergologen, Swiss Society for Allergy and Immunology, Schattauer Allergologie Handbuch, Elsevier Nahrungsmittelallergien und Intoleranzen, Karger Food Allergy: Molecular Basis and Clinical Practice, and Pharmacon. EM reported grants from Reacta Biotech; and was shareholder of Reacta Biotech Ltd. RR reported personal fees from HAL Allergy BV, Citeq BV, Angany Inc., and ThermoFisher Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Datema, Lyons, Fernández-Rivas, Ballmer-Weber, Knulst, Asero, Barreales, Belohlavkova, de Blay, Clausen, Dubakiene, Fernández-Perez, Fritsche, Gislason, Hoffmann-Sommergruber, Jedrzejczak-Czechowicz, Jongejan, Kowalski, Kralimarkova, Lidholm, Papadopoulos, Popov, Prado, Purohit, Reig, Seneviratne, Sinaniotis, Vassilopoulou, Versteeg, Vieths, Welsing, Mills, Le, Zwinderman and van Ree.)

We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m 2 ) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73-0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85-1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86-0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35-1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.

Background: This study evaluates the presence of R132H mutation in isocitrate dehydrogenase ( IDH1 ) gene and the vascular endothelial growth factor ( VEGF ) +936 C/T polymorphism in brain tumors. The impact of these genetic alterations on overall survival (OS) and progression free survival (PFS) was evaluated., Methods: A cohort of 80 patients surgically treated at Hospital Clínico San Carlos, Madrid, between March 2004 and November 2012, was analyzed. Tumors were distributed in 73 primary brain tumors (gliomas, meningiomas, hemangiopericytomas and hemangioblastomas) and seven secondary tumors evolved from a low grade glioma, thus providing a mixed sample., Results: IDH1 R132H gene mutation was found in 12 patients (15%) and appears more frequently in secondary tumors (5 (71.4%) whereas in 7 (9.7%) primary tumors ( p  < .001)). The mutation is related to WHO grade II in primary tumors and a supratentorial location in secondary tumors. The OS analysis for IDH1 showed a tendency towards a better prognosis of the tumors containing the mutation ( p  = .059).The IDH1 R132H mutation confers a better PFS ( p  = .025) on primary tumors. The T allele of VEFG +936 C/T polymorphism was found in 16 patients (20%). No relation was found between this polymorphism and primary or secondary tumor, neither with OS or PFS., Conclusions: IDH1 R132H gene mutation is exclusive in supratentorial tumors and more frequent in secondary ones, with a greater survival trend and better PFS in patients who carry it. The T allele of VEGF +936 C/T polymorphism is more common in primary tumors, although there is no statistical relation with survival.

The measurement of the testosterone to epitestosterone ratio (T/E ratio) in urine is often used as a marker for testosterone administration in the doping control field. This study examines the frequencies of the different expression forms of the UGT2B17 gene, and assesses their effects on this marker in volunteer subjects. The sample for this descriptive study was composed of male and female athletes aged between 16 and 55 years old who practiced different sports disciplines. All participants underwent a sports-medical physical examination, and subsequently provided 10 urine samples consecutively over a period of 48 h. The dependent variable examined was T/E and the main independent variable was the UGT2B17 gene polymorphism. During 1 year, 1410 urine samples were obtained from 141 athletes. The frequencies of the three genotypes were as follows: wt homozygotes (ins/ins) 48.2% (n = 68), mutant homozygotes (del/del) 12.1% (n = 17), and heterozygotes (ins/del) 39.7% (n = 56). Genotype distributions varied significantly (P < 0.001) according to ethnicity, 80% of Asian subjects being homozygous for the gene deletion (del/del) compared to 6.9% of Caucasian subjects. A multivariate analysis adjusted for genotype, age, sex, and sports discipline revealed that athletes with the del/del polymorphism showed a significantly lower mean T/E than heterozygotes (ins/del). In contrast, homozygous athletes for the gene insertion (ins/ins) showed higher mean T/E ratios than heterozygotes (ins/del). UGT2B17 gene deletion has a strong influence on the T/E ratio in urine, which is the most efficient indicator of testosterone prohormone misuse. Others factors studied seem not to have such an impact. The genotyping of UGT2B17 is an important source of information for understanding steroid profiling in the doping control field; therefore it is suggested that it be included in the Athletes Biological Passport., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Recent advances in imaging permit radiologic identification of target structures for deep brain stimulation (DBS) for movement disorders. However, these methods cannot detect the internal subdivision and thus cannot determine the appropriate DBS target located within those subdivisions. The aim of this study is to provide a straightforward method to obtain an optimized target (OT) within DBS target nuclei using a widely available navigation system. We used T1- and T2-weighted images, fluid-attenuated inversion recovery (FLAIR) sequence, and diffusion tensor imaging (DTI) of nine patients operated for DBS in our center. Using the StealthViz® software, we segmented the targeted deep structures (subcortical targets) and the anatomically identifiable areas to which these target nuclei were connected (projection areas). We generated fiber tracts from the projection areas. By identifying their intersections with the subcortical targets, we obtained an OT within the DBS target nuclei. We computed the distances from the clinically effective electrode contacts (CEEC) to the OT obtained by our method and the targets provided by the atlas. These distances were compared using a Wilcoxon signed-rank test, with p < 0.05 considered statistically significant. We were able to identify OT coincident with the motor part of the subthalamic nucleus and the ventral intermediate nucleus. We clinically tested the results and found that the CEEC were significantly more closely related to the OT than with the targets obtained by the atlas. Our present results show that this novel method permits optimization of the stimulation site within the internal subdivisions of target nuclei for DBS.

Background: Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens., Objective: Establishing a molecular map of hazelnut allergy across Europe., Methods: In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP., Results: Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen., Conclusions: In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is associated with numerous metabolic complications such as diabetes mellitus type 2, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. Our goal was to compare different criteria to define the metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) subjects. We applied Wildman (W), Wildman modified (WM) with insulin resistance (IR) with cut-off point ≥ 3.8 and levels of C- Reactive Protein (CRP) ≥ 3 mg/l; and Consensus Societies (CS) criteria. In these subjects cardiovascular-risk (CV-risk) was estimated by Framingham score and SCORE for MHO and MUHO., Methods: A cross-sectional study was conducted in Spanish Caucasian adults. A total of 3,844 subjects completed the study, 45% males, aged 35-74 years. Anthropometric/biochemical variables were measured. Obesity was defined as BMI: ≥ 30 Kg/m(2)., Results: The overall prevalence of obesity in our population was 27.5%, (23.7%/males and 30.2%/females). MHO prevalence according to W, WM, and CS definition criteria were: 9.65%, 16.29%, 39.94% respectively in obese participants. MHO has lower waist circumference (WC) measurements than MUHO. The estimated CV-risks by Framingham and SCORE Project charts were lower in MHO than MUHO subjects. WC showed high specificity and sensitivity in detecting high estimated CV risk by Framingham. However, WHR showed high specificity and sensitivity in detecting CV risk according to SCORE Project. MHO subjects as defined by any of the three criteria had higher adiponectin levels after adjustment by sex, age, WC, HOMA IR and Framingham or SCORE risks. This relationship was not found for CRP circulating levels neither leptin levels., Conclusions: MHO prevalence is highly dependent on the definition criteria used to define those individuals. Results showed that MHO subjects had less WC, and a lower estimated CV-risk than MUHO subjects. Additionally, the high adiponectin circulating levels in MHO may suggest a protective role against developing an unhealthy metabolic state.

Objective: To describe growth and neurodevelopmental status of 4,944 children who completed a follow-up at two years of corrected age out of the 10,456 newborns with weight ≤1500g born between the years 2002-2007 and discharged from hospitals within the network SEN1500. A total of 522 newborns were excluded as they had some type of malformation. The total number of children assessed represents the 49.76% of children discharged alive and without malformations., Methods: A retrospective review was conducted using prospectively collected data in the SEN1500 database. We compared growth data at two years of corrected age according to birth weight and sex. Motor impairment, incidence of cerebral palsy, visual and hearing disabilities, and abnormal neurodevelopment for gestational age were analysed between groups. We studied the associations between cerebral palsy (CP) and perinatal factors., Results: At 2 years of age 44.2% of children had a weight <2 SD for corrected age. Children with birth weight ≤1000g showed worse outcomes in growth. Some type of motor impairment was observed in 6.96% of the infants, and 4.56% of them were diagnosed with CP. The incidence was higher among males with birth weight ≤1000g. There was an incidence of 5.21% of visual disability, with 0.5% of children being blind in one or both eyes. Cerebral palsy was associated with retinopathy of prematurity, severe intraventricular haemorrhage, and periventricular leukomalacia, in particular cystic periventricular leukomalacia., (Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)