Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluación de la resistencia a prodiplosis longifila gagné (diptera: cecidomyiidae) en genotipos de tomate cultivados y silvestres

Se evaluó la resistencia a Prodiplosis longifila Gagné en tres accesiones silvestres de Solanum habrochai-tes var. glabratum (PI-134417, PI-134418 y PI-126449) y los materiales avanzados en mejoramiento genéti-co para resistencia al pasador del fruto Neoleucinodes elegantalis: tres genotipos de retrocruzamiento 3: RC3(3143P4, 3247P4, 36110P3) y un genotipo de retrocruzamiento 4: RC4(4212P4), como testigo susceptible se incluyó la variedad Solanum lycopersicum cv. Unapal-Maravilla. Las evaluaciones se realizaron en condiciones de campo y de casa de malla, utilizando un diseño de bloques completos al azar con cuatro repeticiones. Se evaluó el número de brotes sanos/planta, número de brotes con daño por P. longifila, número de brotes con presencia de larvas vivas y muertas del insecto, y número de larvas vivas o muertas por brote. Durante el experimento en campo las poblaciones de P. longifila fueron 0.2 larvas vivas/brote y 4.17% de daño, lo cual no permitió el establecimiento de diferencias entre los genotipos estudiados. En casa de malla, las poblaciones del insecto fueron elevadas,sin embargo las accesiones silvestres no mostraron daño ni fueron preferidas para la oviposición, presentando algún grado de resistencia. Unapal-Maravilla y los genotipos correspondientes a la RC3, fueron susceptibles al insecto. El genotipo 4212P4 mostró el menor daño de las poblaciones segregantes con solo 5.36% de brotes dañados, siendo considerado como de menor preferencia por el insecto plaga. Los genotipos provenientes de retrocruzamientos evaluados en estos ensayos fueron previamente seleccionad por resistencia a N. elegantalis, y en este procedimiento es posible que hayan podido descartarse genotipos con resistencia a P. longifila.Resistance was evaluated Prodiplosis longifila Gagné in three wild accessions Solanum habrochaites var. glabratum ( PI134417 , PI134418 and PI 126449 ) and advanced materials in breeding for resistance to fruit borer Neoleucinodes elegantalis : three genotypes of three backcross RC3 ( 3143P4 , 3247P4 , 36110P3 ) and four backcross genotype RC4 (4212P4 ) as susceptible check variety S. lycopersicum cv. Unapal - Maravilla.  Evaluations were performed under field conditions and screen house, using a completely randomized design with four replications. Number of healthy / plant, number of shoots sprout damage was assessed with P. longifila , number of shoots with the presence of live and dead and number of living and dead larvae larvae per shoot . During the experiment field populations of P. longifila were 0.2 live larvae / shoot and 4.17 % damage, which prevented the establishment of differences between the genotypes studied. In screen house, insect populations were high, however wild accessions showed no damage, nor were preferred for oviposition , showing some degree of resistance . Unapal - Maravilla and genotypes corresponding to the RC3, were susceptible to insect. 4212P4 genotype showed the least damage of segregating populations with only 5.36% of shoots damaged, regarded as less preferred by the insect pest. Genotypes from backcrosses evaluated in these trials had previous selection toward resistance N. elegantalis, and in this process they may have been discarded genotypes with resistance to P. longifila

Evaluación de la resistencia a prodiplosis longifila gagné (diptera: cecidomyiidae) en genotipos de tomate cultivados y silvestres

Se evaluó la resistencia a Prodiplosis longifila Gagné en tres accesiones silvestres de Solanum habrochai-tes var. glabratum (PI-134417, PI-134418 y PI-126449) y los materiales avanzados en mejoramiento genéti-co para resistencia al pasador del fruto Neoleucinodes elegantalis: tres genotipos de retrocruzamiento 3: RC3(3143P4, 3247P4, 36110P3) y un genotipo de retrocruzamiento 4: RC4(4212P4), como testigo susceptible se incluyó la variedad Solanum lycopersicum cv. Unapal-Maravilla. Las evaluaciones se realizaron en condiciones de campo y de casa de malla, utilizando un diseño de bloques completos al azar con cuatro repeticiones. Se evaluó el número de brotes sanos/planta, número de brotes con daño por P. longifila, número de brotes con presencia de larvas vivas y muertas del insecto, y número de larvas vivas o muertas por brote. Durante el experimento en campo las poblaciones de P. longifila fueron 0.2 larvas vivas/brote y 4.17% de daño, lo cual no permitió el establecimiento de diferencias entre los genotipos estudiados. En casa de malla, las poblaciones del insecto fueron elevadas,sin embargo las accesiones silvestres no mostraron daño ni fueron preferidas para la oviposición, presentando algún grado de resistencia. Unapal-Maravilla y los genotipos correspondientes a la RC3, fueron susceptibles al insecto. El genotipo 4212P4 mostró el menor daño de las poblaciones segregantes con solo 5.36% de brotes dañados, siendo considerado como de menor preferencia por el insecto plaga. Los genotipos provenientes de retrocruzamientos evaluados en estos ensayos fueron previamente seleccionad por resistencia a N. elegantalis, y en este procedimiento es posible que hayan podido descartarse genotipos con resistencia a P. longifila.Resistance was evaluated Prodiplosis longifila Gagné in three wild accessions Solanum habrochaites var. glabratum ( PI134417 , PI134418 and PI 126449 ) and advanced materials in breeding for resistance to fruit borer Neoleucinodes elegantalis : three genotypes of three backcross RC3 ( 3143P4 , 3247P4 , 36110P3 ) and four backcross genotype RC4 (4212P4 ) as susceptible check variety S. lycopersicum cv. Unapal - Maravilla.  Evaluations were performed under field conditions and screen house, using a completely randomized design with four replications. Number of healthy / plant, number of shoots sprout damage was assessed with P. longifila , number of shoots with the presence of live and dead and number of living and dead larvae larvae per shoot . During the experiment field populations of P. longifila were 0.2 live larvae / shoot and 4.17 % damage, which prevented the establishment of differences between the genotypes studied. In screen house, insect populations were high, however wild accessions showed no damage, nor were preferred for oviposition , showing some degree of resistance . Unapal - Maravilla and genotypes corresponding to the RC3, were susceptible to insect. 4212P4 genotype showed the least damage of segregating populations with only 5.36% of shoots damaged, regarded as less preferred by the insect pest. Genotypes from backcrosses evaluated in these trials had previous selection toward resistance N. elegantalis, and in this process they may have been discarded genotypes with resistance to P. longifila

Accidente cerebro vascular por embolismo paradójico en paciente adolescente

Stroke is an inusual cause of pediatric urgency. In around 40% of them, no cause is identified despite extensive tests.Cerebrovascular ischemic events can be attribuided to paradoxical embolism trough a patent foramen ovale.El accidente cerebrovascular es una causa poco frecuente de urgencia en la edad pediátrica. En aproximadamente el 40% de los casos no se identifica la causa a pesar de las pruebas complementarias realizadas. Los episodios de isquemia cerebrovascular pueden atribuirse a embolismo paradójico a través de foramen oval permeable

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization