[Choice of Family and Community Medicine in the MIR 2002-2023: An objective approach shows that it is as highly valued as hospital specialties]. / Elección de Medicina Familiar y Comunitaria en el MIR 2002-2023: un enfoque objetivo muestra que es una especialidad tan valorada como las hospitalarias.

INTRODUCTION: Currently there is a shortage of general practitioners (GP), and this is expected to increase in the coming years. Despite this need, it is a specialty that is supposedly little demanded, leaving specialized training places unfilled in recent years. The purpose of this study is to present new parameters to more objectively measure the demand and the relationship between supply and demand. METHODS: A database was used with the results of the places assigned in the MIR calls from 2002 to 2023. The calculated parameters were quoting index (CI), quote order, the order of top demand and the order of total demand of the GP specialty. The software R version 4.3.02 was used for statistical analysis. RESULTS: The specialty quotation and top demand have remained constant during the study period, while there has been a slight and progressive worsening of the total demand. Nevertheless, the total demand for Family Medicine in the last call for MIR exam was higher than that for specialties such as urology, neurology, ENT, endocrinology, oncology, intensive care medicine or neurosurgery, among others. CONCLUSIONS: In contrast to the subjective perception of the worsening attractiveness Family Medicine in the last MIR calls, using objective parameters, we found that the attractiveness of the specialty, measured as quotation (supply/demand ratio) and demand, has remained stable (with a slight worsening of total demand).

[Evaluation of healthcare for patients with diabetes in primary care: A systematic review]. / Evaluación de la asistencia sanitaria del paciente con diabetes en atención primaria: una revisión sistemática.

OBJECTIVE: Have the most current evidence in relation to the evaluation of medical healthcare for patients with diabetes in primary care. METHOD: During the review process, we followed the recommendations to improve the publication of systematic reviews and meta-analyses and the preferred reporting points for PRISMA systematic reviews. The bibliographic search was carried out in Cumulative Index to Nursing and Allied Health Literature (CINAHL), SCOPUS, Scielo, MedLine/ PubMed, Cochrane databases and in the Google Scholar search engine, with free and controlled language, using the MeSh search terms: «Physicians, Primary Care¼, «Diabetes Mellitus, Type2¼. Eight selected articles were analyzed. The articles were selected based on their relevance, published in peer-reviewed academic journals and published between 2019 and 2023. RESULTS: The main study tool represents interventions in knowledge and practice about the care of patients with diabetes among primary care physicians. The most important discussion topics extracted in the analyzed articles refer to knowledge, clinical inertia, patients' housing challenges, adherence intervention programs, and a self-care application for patients with diabetes. CONCLUSIONS: The findings of this study indicate the need to improve medical health care through knowledge, attitudes and practices in primary care regarding patients with diabetes. In this way, it could be considered a useful tool to promote medical healthcare in primary care.

[Seizures in the emergency service: the clinical and therapeutic characteristics of 122 patients]. / Crisis en urgencias: una vista a las características clínicas y terapéuticas a través de 122 pacientes.

INTRODUCTION: Epileptic seizures are a common cause of admission in emergency services at hospitals. Performing the correct diagnosis can be difficult, and deciding when and which anti-seizure medication (ASM) to prescribe is critical. Our objective is to detail the characteristics of patients treated in a medium-sized hospital for this reason. PATIENTS AND METHODS: A retrospective observational study was performed, including all the adult patients treated by the emergency service of the Lucus Augusti University Hospital between January 2022 and January 2023 with a diagnosis of epileptic seizure on discharge. The study recorded their demographic variables, history, whether it was their first seizure, the number of seizures, whether an anti-seizure medication was administered and which one, the diagnosis, the tests performed, and whether the patient was referred to the neurology service. RESULTS: A total of 122 patients were diagnosed with epileptic seizures in the emergency service. 50.8% of the patients were women. The mean age was 69.8 years. Neurological assessment was requested for 47.6%. 50.8% presented their first seizure. No diagnosis was performed in 46% of the cases, of which only 10 were evaluated by the neurology service. The most common etiology was vascular. An electroencephalogram was performed on 41.8%. Levetiracetam was practically the only drug administered when the neurology department was not consulted. CONCLUSIONS: Early evaluation of patients with their first seizure in the emergency service by a neurological specialist is crucial for the diagnosis of epilepsy. The same anti-seizure medication is almost always prescribed when no cross-consultation takes place.

TITLE: Crisis en urgencias: una vista a las características clínicas y terapéuticas a través de 122 pacientes.Introducción. Las crisis epilépticas son un motivo frecuente de consulta en los servicios de urgencias hospitalarias. Llegar al diagnóstico correcto puede ser complejo, y es fundamental decidir cuándo y qué medicamento anticrisis (MAC) pautar. Nuestro objetivo es detallar las características de los pacientes que consultaron por este motivo en un hospital mediano. Pacientes y métodos. Estudio observacional retrospectivo de todos los pacientes mayores de edad que consultaron en el servicio de urgencias del Hospital Universitario Lucus Augusti entre enero de 2022 y enero de 2023 con diagnóstico al alta de crisis epiléptica. Se registraron variables demográficas, los antecedentes, si era una primera crisis, el número de éstas, si se inició un MAC y cuál, el diagnóstico, qué pruebas se realizaron y si se interconsultó con la guardia de neurología. Resultados. Se diagnosticó a 122 pacientes de crisis epilépticas en urgencias. El 50,8% eran mujeres. La media de edad fue de 69,8 años. Se solicitó valoración por neurología en un 47,6%. El 50,8% presentó una primera crisis. No se llegó al diagnóstico en un 46% de los casos, de los cuales sólo 10 fueron valorados por neurología. La etiología más frecuente fue la vascular. Se realizó un electroencefalograma en un 41,8%. El levetiracetam fue prácticamente el único fármaco utilizado cuando no se consultó con neurología. Conclusiones. La valoración precoz de los pacientes con una primera crisis en urgencias por un especialista en neurología es determinante para el diagnóstico de epilepsia. Cuando no se interconsulta, casi siempre se pauta el mismo MAC.

Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Phase transition in the computational complexity of the shortest common superstring and genome assembly.

Genome assembly, the process of reconstructing a long genetic sequence by aligning and merging short fragments, or reads, is known to be NP-hard, either as a version of the shortest common superstring problem or in a Hamiltonian-cycle formulation. That is, the computing time is believed to grow exponentially with the problem size in the worst case. Despite this fact, high-throughput technologies and modern algorithms currently allow bioinformaticians to handle datasets of billions of reads. Using methods from statistical mechanics, we address this conundrum by demonstrating the existence of a phase transition in the computational complexity of the problem and showing that practical instances always fall in the "easy" phase (solvable by polynomial-time algorithms). In addition, we propose a Markov-chain Monte Carlo method that outperforms common deterministic algorithms in the hard regime.

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P =  .03), focal deficits (P = .001), and encephalopathy (P < .001) showing a statistically significant association with poor prognosis (mRS > 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

Detection and characterisation of visual field defects using Octopus perimetry in congenital glaucoma.

PURPOSE: To detect and characterise visual field (VF) defects using static Octopus perimetry in patients with primary congenital glaucoma (PCG) and to determine VF quality and time duration. MATERIAL AND METHODS: Eighty-eight eyes of 70 patients diagnosed with PCG were included. Assessments were performed using an Octopus 900 and each eye was assessed with the tendency-oriented perimetry (G-TOP) algorithm. Quantitative VF data were collected: quality data (false positive and negative response, and time duration) and results of mean deviation (MD) and square root of loss variance (sLV). Qualitative data were collected: the presence of diffuse and localized defects, the affected hemifield and grade of defects using the Aulhorn and Karmeyer classification. Correlations between perimetric results and clinical variables were analysed. RESULTS: Median age was 11 (8-17) years. 65.9% (58/88) of PCG eyes showed VF defects. Diffuse defects were observed in 10/58 eyes (16.94%) (mean MD = 23.92 [SD: 2.52]) dB) and localized defects in 48/58 eyes (82.75%). The most frequent defect was spot-like/stroke-like/incipient paracentral scotoma (n = 15), nasal step (n = 8), adding arcuate defect (n = 2), half ring-shaped (n = 13) and concentric defect with a central island (n = 9). And the most frequent affected visual hemifield was inferior hemifield. Mean test duration was 2 min 12 s (SD: 21.6 s). MD and sLV values were correlated with best corrected visual acuity (BCVA), cup to disc ratio and number of antiglaucoma surgeries (all P < .001). CONCLUSION: A high number of diffuse and localized defects were identified using Octopus perimetry in PCG patients. The most frequent defect was paracentral scotoma and inferior hemifield was the most affected.

[Efficacy and safety of pediatric flu vaccination: a systematic review]. / Eficacia y seguridad de la vacunación antigripal pediátrica: una revisión sistemática.

OBJECTIVE: Children are at a higher risk of influenza infection compared to the general population. The World Organization Health and recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics contemplate annual vaccination as the most effective way to prevent the disease. Therefore, the purpose of this review was to update information on efficacy and safety in the anti -shed vaccine in children and adolescents. METHODS: A search in four electronic databases (Scopus, Cumulative Index to Nursing and Allied Health Literature, Medline / Pubmed, Google Scholar and Cochrane), as well as a manual search to identify original research published between 2012 and 2022. The guidelines of ANALYSIS (PRISMACR) as a preferred report element for systematic reviews. RESULTS: Seven original research articles were included where two issues of antigripal vaccination were identified in healthy children/adolescents and with pathologies. The efficacy (between approximately 30% and 80%) varied depending on the vaccine used and circulating subtypes. Most adverse reactions were mild intensity, and the most common local adverse event was pain in the injection site. CONCLUSIONS: We positively highlight the safety of pediatric flu vaccination in analyzed studies, on the contrary, with respect to the efficacy of flu vaccination, we observe a wide variability of results. There is a clear need to continue conducting efficacy and safety studies in the child.

Transdiagnostic inflammatory and oxidative biomarkers with predictive capacity of self-injurious behavior in impulsive and unstable disorders.

INTRODUCTION: Alterations in inflammatory processes have previously been reported in impulsive and unstable disorders, as well as in other psychiatric conditions. In order to investigate transdiagnostic biomarkers associated with various phenotypic features of these disorders, this study is designed to identify biomarkers of inflammatory and oxidative endophenotypes related to autolytic behavior. METHODS: Peripheral blood mononuclear cells were collected from 35 patients with borderline personality disorder (BPD), 29 patients with restrictive eating disorder (rED), 21 patients with purging eating disorder (pED) and 23 control subjects. Plasma levels of different inflammatory and oxidative factors were measured by ELISA and the expression of selected proteins was by Western Blot. Principal component analysis (PCA) was performed to categorize the different inflammatory factors. Additionally, Ancova was performed to observe the differences in the principal components among the different groups and logistic regression analysis was conducted to assess the predictive capacity of these components for autolytic behaviors. RESULTS: We found two inflammatory/oxidative components were associated with BPD, characterized by high levels of JNK and ERK and low levels of GPx, SOD and Keap1; and two other inflammatory/oxidative components were linked to pED, associated with more JNK, TBARS and TNF-α and less GPx and SOD. Two components, with more JNK and ERK and less GPx, SOD and Keap1, predicted non-suicidal self-injury and three components, with higher JNK, TBARS and TNF-α levels and lower GPx, SOD and iNOS levels, predicted suicide attempts. CONCLUSIONS: These results strongly support the endophenotypic characterization of impulsivity and the identification of transdiagnostic inflammatory/oxidative biomarkers relevant to autolytic behavior in impulsive and unstable disorders. These dates lay the groundwork for developing of screening tests for these biomarker components to rapidly detect biological risk factors for specific impulse control disorders and future self-injurious behaviors.

Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders.

INTRODUCTION: This study aims to enhance the understanding of the association between the phenotypic and endophenotypic characteristics of impulsive-aggressive disorders, through the study of plasma oxytocin (OXT) and oxytocin receptor (OXTR) levels in patients with borderline personality disorder (BPD) and patients with eating disorders (ED), as well as to examine the relationship of OXT system with aggressive behavior in these disorders. METHODS: 68 patients with BPD, 67 patients with ED and 57 healthy control subjects were examined for plasma oxytocin levels and protein expression of OXTR in blood mononuclear cells. Aggressive behavior was assessed using the State-Trait Anger Expression Inventory (STAXI-2). Other self and hetero-aggressive behaviors were also evaluated through interviews. RESULTS: BPD and ED patients exhibited significantly lower plasma oxytocin levels than control subjects. Furthermore, BPD patients demonstrated significantly reduced expression of OXTR compared to controls. Plasma oxytocin levels negatively correlated with verbal aggression, while OXTR expression was inversely associated with the STAXI trait subscale. CONCLUSIONS: The findings validate the existence of oxytocin system dysfunction in impulsive-aggressive disorders. They also support the link between low OXT levels in plasma and OXTR expression and the impulsive-aggressive behavior that characterizes these patients in both state and trait situations.

Diagnostic ability of vessel density of the optic nerve head and macula versus structural parameters with optical coherence tomography in pseudoexfoliative glaucoma.

PURPOSE: To evaluate the diagnostic ability of the vessel density (VD) of the optic nerve head (ONH) and the macula on optical coherence tomography (OCT) angiography and the retinal nerve layer thickness (RNFL) thickness and the macular ganglion cell complex (GCC) thickness on OCT in patients with pseudoexfoliative glaucoma (PXG). METHODS: Cross-sectional study including PXG patients and healthy controls. Demographic and clinical data were noted for all participants. Optical coherence tomography (OCT) and OCT angiography (OCTA) images of the ONH and macular area were obtained with the RS-3000 Advance OCT (Nidek Co., Gamagori, Japan). The RNFL and GCC thickness of different sectors was provided by the software. Macular VD of the superficial capillary plexus (SCP) and ONH VD of the radial peripapillary capillary plexus (RPCP) were registered. Groups were compared and area under the receiver operating characteristic (AUROC) curves were used to determine the power of discrimination of each parameter. RESULTS: RNFL and GCC thickness and ONH and macular VD were significantly lower in PXG patients compared with healthy controls (all, p<0.05). The best discrimination parameter was the average RNFL thickness (AUROC: 0.928). ONH VD AUROC was better than that of macular VD (AUROC: 0.897 and 0.780, respectively). ONH VD AUROC was comparable to RNFL thickness (p<0.001). CONCLUSIONS: The diagnostic ability of ONH vessel density in PXG appears comparable to that of the structural parameters, RNFL and GCC thickness, obtained with OCT, and may be a valuable tool in clinical practice.

Androgen deprivation therapy in localized prostate cancer. Current status and future trends.

INTRODUCTION: Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. OBJECTIVE: To summarize the current indications of ADT in localized PCa. EVIDENCE ACQUISITION: We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. EVIDENCE SYNTHESIS: Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT < 12 months, and either a PSA > 50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. CONCLUSIONS: We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment.

Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration.

OBJECTIVE: To analyse the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3). RESULTS: The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years. CONCLUSION: Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.

Tuning the carrier injection barrier of hybrid metal-organic interfaces on rare earth-gold surface compounds.

Magnetic hybrid metal-organic interfaces possess a great potential in areas such as organic spintronics and quantum information processing. However, tuning their carrier injection barriers on-demand is fundamental for the implementation in technological devices. We have prepared hybrid metal-organic interfaces by the adsorption of copper phthalocyanine CuPc on REAu2 surfaces (RE = Gd, Ho and Yb) and studied their growth, electrostatics and electronic structure. CuPc exhibits a long-range commensurability and a vacuum level pinning of the molecular energy levels. We observe a significant effect of the RE valence of the substrate on the carrier injection barrier of the hybrid metal-organic interface. CuPc adsorbed on trivalent RE-based surfaces (HoAu2 and GdAu2) exhibits molecular level energies that may allow injection carriers significantly closer to an ambipolar injection behavior than in the divalent case (YbAu2).

Tuning the aspect ratio of silver nanospheroids embedded in silica: erratum.

We present a corrigendum to our Letter [Opt. Lett.35, 703 (2010)10.1364/OL.35.000703]. In the original Letter we inadvertently included in Fig. 2(a) a TEM micrograph corresponding to a different, but very similar, sample. This corrigendum replaces Fig. 2(a) with a correct version. Since the main results are rather based in optical absorption measurements, and their modeling by using the T-matrix method, this correction does not affect the results and conclusions of the original Letter.

Analysis of the influence of corneal properties and densitometry on applanation and rebound tonometry in primary open angle glaucoma.

PURPOSE: To evaluate the influence of corneal densitometry on portable applanation (Perkins) and rebound (iCare ic100 and PRO) tonometry. A secondary goal was to assess if there was a relationship between various corneal properties and the severity of primary open angle glaucoma (POAG). MATERIAL AND METHODS: Seventy-five eyes of 75 patients with primary open angle glaucoma were studied, divided by severity into 3 groups: 25 mild, 25 moderate and 25 advanced. Intraocular pressure (IOP) was measured 3 times in each participant with a Perkins applanation tonometer (PAT), a handheld version of the Goldman applanation tonometer (GAT), an iCare PRO and an iCare ic100. Mean values were then calculated. Corneal topography with the Pentacam HR (Oculus, Wetzlar, Germany) was also performed in all individuals. RESULTS: Mean age and sex were comparable in all groups, as were densitometry values (P>0.05). The mean visual field defect (MD) was 2.85 (±1.23) dB in the mild glaucoma group, 8.26 (±1.90) dB in the moderate group and 15.66 (±3.46) dB in the advanced group. Three multivariate regression analyses were performed. The first and second calculations assessed the effect of IOP obtained with iCare ic100 and PAT as dependent variables with age, sex, CCT and mean keratometry (Km) within the glaucoma subgroups and the global sample. The third analysis was carried out to assess the relationship between corneal densitometry as the dependant variable and the aforementioned corneal parameters among the glaucoma groups. In the first multivariate regression analysis, a statistically significant correlation was found between ic100 rebound tonometry and CCT in the POAG global sample (coef. 0.117; IC [-0.21-(-0.01)]; P=0.025). No statistically significant correlation was found in the subgroup analyses. In the second multivariate analysis, no significant correlation was found between PAT and CCT, Km, age or sex (P>0.05). In the third analysis, densitometry was correlated with age in all glaucoma subgroups (P<0.001) and with CCT in the moderate glaucoma subgroup (coef. -0.037; IC [-0.67-(-0.01)]; P=0.021). Tonometry appeared to be minimally influenced by corneal densitometry, with a mild positive linear correlation seen (R=0.03). IOP values were similar with 3 of the tonometers: PAT 16.07 (±3.18) mmHg, PRO 16.27 (±3.42) mmHg and ic100 15.17 (±4.28) mmHg. There was, however, a significant underestimation of IOP with ic100 (-0.89mmHg) compared to PAT (P=0.007). CONCLUSION: Corneal densitometry did not show significant differences between glaucoma severity groups. A positive correlation was seen with CCT and both corneal densitometry and age. No correlation was found with keratometry or severity of glaucoma. The influence of corneal densitometry on IOP measurements appears weak, with little clinical relevance identified.

Single nucleotide polymorphisms in ADAM17, IL23R and SLCO1C1 genes protect against infliximab failure in adults with Crohn's disease.

BACKGROUND: To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AIM: We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. METHODS: A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. RESULTS: Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). CONCLUSIONS: SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.