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1.
Artículo en Inglés | MEDLINE | ID: mdl-39087442

RESUMEN

OBJECTIVE: Understanding the local characteristics and statistics related to stillbirths may be the first step in a series of strategies associated with a reduction in stillbirth ratio. The aim of this study was to estimate the fetal mortality ratio and evaluate the investigation processes related to the causes of death, comparing the investigation according to the specific cause of death. METHODS: A cross-sectional study was retrospectively conducted in 10 tertiary obstetric care centers. Medical records of women with stillbirth managed between January 1, 2009 and December 31, 2018 were analyzed and classified, according to sociodemographic characteristics, and gestational and childbirth data, culminating in stillbirth. The stillbirth ratio and its causes were presented in proportions for the study period and individually for each health facility. RESULTS: Cases of 3390 stillbirths were analyzed. The stillbirth ratio varied from 10.74/1000 live births (LBs) in 2009 to 9.31/1000 in 2018. "Intrauterine hypoxia and asphyxia" (ICD-10 P20) and "unspecific causes of death" (ICD-10 P95) represented 40.8% of the causes of death. Investigation for TORCHS and diabetes occurred in 90.8% and 61.4% of deaths, respectively. Placental and necroscopic tests were performed in 36.6% of the cases. CONCLUSION: The adoption of a rational and standardized investigation of stillbirth remains an unmet need; the use of additional tests and examinations are lacking, especially when unspecific causes are attributed.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39039360

RESUMEN

INTRODUCTION: Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. METHODS: This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). RESULTS: A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. CONCLUSIONS: This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.

5.
Clin Res Hepatol Gastroenterol ; 48(7): 102416, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986810

RESUMEN

BACKGROUND AND AIMS: The prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention. METHODS: A cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years). RESULTS: A total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered "rare" by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity. CONCLUSION: The current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

6.
J Affect Disord ; 363: 106-111, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39025445

RESUMEN

BACKGROUND: Suicide ranks as a leading cause of premature death among adolescents globally. Understanding the trends and key determinants of suicidal behavior in youth are critical for implementing educational policies and supporting preventive strategies in schools. METHODS: This retrospective study examined all hospitalizations due to suicidal behavior in children and adolescents aged 11 to 18 years in Spain, using data from the Spanish National Registry of Hospital Discharges spanning 2000 to 2021. RESULTS: Over the 22-year study period, there were 2,015,589 hospitalizations among adolescents in Spain, with 118,609 (5.9 %) cases involving mental disorders. There were 2855 admissions with suicidal behavior, constituting 2.4 % of the hospitalizations among youth with mental disorders. Girls represented 73.4 % of all hospitalizations, with a median age of 16 years. Admissions for suicidal behavior saw a four-fold increase during the last decade (p < 0.001). The in-hospital mortality rate for adolescents with suicidal behavior doubled that of those hospitalized for other mental disorders. During the first year of the COVID-19 pandemic, admissions of adolescents with suicidal behavior decreased, only to surge by 2.5-fold during 2021. CONCLUSION: Hospital admissions for suicidal behavior among adolescents have risen in Spain over the last two decades. Girls represented 73.4 % of these admissions, yet in-hospital mortality was more frequent in boys.

7.
Heliyon ; 10(12): e32794, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975128

RESUMEN

Thermoplastic polyurethane (TPU) doped with multi-walled carbon nanotubes (MWCNTs) at 1, 3, 5, and 7 wt% has been studied. The effect of MWCNTs on thermal, viscoelastic, and electric properties in the TPU matrix was characterized by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and by impedance spectroscopy. The results show that the thermal, electrical, and viscoelastic properties, such as the glass transition temperature, shifted towards high temperatures. The melting temperature decreased, and the conductivity and the storage modulus increased by 61.5 % and 58.3 %. The previously observed behavior on the films is due to the increase in the mass percentage of carbon nanotubes (CNTs) in the TPU matrix. Also, it can be said that the CNTs were homogeneously dispersed in the TPU matrix, preventing the movement of the polymer chains, and generating channels or connections that increase the conductivity and improve the thermal properties of the material.

8.
Biol Open ; 13(7)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39078271

RESUMEN

Although some budding yeasts have proved tractable and intensely studied models, others are more recalcitrant. Debaryomyces hansenii, an important yeast species in food and biotechnological industries with curious physiological characteristics, has proved difficult to manipulate genetically and remains poorly defined. To remedy this, we have combined live cell fluorescent dyes with high-resolution imaging techniques to define the sub-cellular features of D. hansenii, such as the mitochondria, nuclei, vacuoles and the cell wall. Using these tools, we define biological processes like the cell cycle, organelle inheritance and various membrane trafficking pathways of D. hansenii for the first time. Beyond this, reagents designed to study Saccharomyces cerevisiae proteins were used to access proteomic information about D. hansenii. Finally, we optimised the use of label-free holotomography to image yeast, defining the physical parameters and visualising sub-cellular features like membranes and vacuoles. Not only does this work shed light on D. hansenii but this combinatorial approach serves as a template for how other cell biological systems, which are not amenable to standard genetic procedures, can be studied.


Asunto(s)
Debaryomyces , Proteómica/métodos , Vacuolas/ultraestructura , Vacuolas/metabolismo , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Saccharomyces cerevisiae/ultraestructura
9.
Sports Biomech ; : 1-15, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915207

RESUMEN

The aim of this study was to explore the reliability and feasibility of the isometric mid-thigh pull (IMTP) and dynamic strength index (DSI) in semi-professional handball players (seventeen male and eighteen female). A cross-sectional design was used to determine the test-retest reliability of several kinetic metrics registered with a force plates. The peak force, peak relative force, rate of force development (RFD 0-250 ms), and impulse 0-250 ms were selected from the IMTP test, whereas the peak propulsive force was chosen from the countermovement jump test to obtain the DSI. The intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of the measurement (SEM) and smallest detectable difference (SDD) were calculated. A paired sample t-test was also performed. No significant differences were found between the testing sessions for all variables, except for peak propulsive force for all players (p = 0.036) and DSI for female players (p = 0.037). Reliability for all kinetic metrics was good to excellent (ICC = 0.78-0.97), with low variability (CV ≤ 8.64%), being the SEM scores lower than SDD. In conclusion, the IMTP test and DSI are highly reliable and feasible tools for assessing neuromuscular performance in semi-professional handball players.

10.
Eur J Pediatr ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916739

RESUMEN

An early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. The objectives were (i) to analyze the characteristics of miRNA expression and metabolic patterns of neonates with NE and (ii) to assess their predictive performance for neurodevelopmental outcomes. Plasma samples from moderate/severe NE patients (N = 92) of the HYPOTOP study were collected before, during, and after therapeutic hypothermia (TH) and compared to a control group (healthy term infants). The expression of miRNAs and concentrations of metabolites (hypoxia-related and energy, steroid, and tryptophan metabolisms) were analyzed. Neurodevelopmental outcomes were evaluated at 24 months postnatal age using Bayley Scales of Infant Development, ed. III, BSID-III. Differences in miRNA and metabolic profiles were found between NE vs. control infants, abnormal (i.e., mildly and moderately abnormal and severe) vs. normal, and severe vs. non-severe (i.e., normal and mildly and moderately abnormal) BSID-III. 4-Androstene-3,17-dione, testosterone, betaine, xanthine, and lactate were suitable for BSID-III outcome prediction (receiver operating characteristic areas under the curve (AUCs) ≥ 0.6), as well as 68 miRNAs (AUCs of 0.5-0.9). Significant partial correlations of xanthine and betaine levels and the expression of several miRNAs with BSID-III sub-scales were found. Conclusion: We have identified metabolites/miRNAs that might be useful to support the prediction of middle-term neurodevelopmental outcomes of NE. What is known and what is new: • The early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. • Alterations of the metabolome and miRNAs had been observed in NE. • We performed miRNA sequencing and quantified selected metabolites (i.e., lactate, pyruvate, ketone bodies, Krebs cycle intermediates, tryptophan pathway, hypoxia-related metabolites, and steroids) by GC- and LC-MS. • Specific miRNAs and metabolites that allow prediction of middle-term neurodevelopmental outcomes of newborns with NE undergoing hypothermia treatment were identified.

11.
Childs Nerv Syst ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937287

RESUMEN

INTRODUCTION: During infancy, infectious aneurysms are uncommon and potentially fatal lesions with an imminent risk of intracranial hemorrhage development. CASE PRESENTATION: A 1-month-old infant presented with loss of consciousness and clonic movements of the right superior limb after a work-up for Hirschsprung's disease. His physical exam revealed stupor, miosis, anterior fontanelle swelling, and hyperreflexia of the right superior limb. Blood cultures were positive for Candida albicans. In addition, brain imaging revealed an intraparenchymal hematoma in the left temporal lobe and a saccular aneurysm at the M3 segment of the left middle cerebral artery. Upon careful discussion with the patient's family, he underwent evacuation of the hematoma and aneurysm repair. His postoperative clinical course was uneventful. At the 5-month follow-up, a brain MRI showed encephalomalacia in the area of prior hemorrhage. Furthermore, he had preserved motor function and adequate psychomotor development on subsequent pediatric evaluations. CONCLUSION: Microsurgical management of ruptured mycotic aneurysms demands a systematic work-up and nuanced appraisal of clinical and aneurysmal factors. Operating in a confined space and considering the fragile nature of aneurysms are of utmost relevance for effectively treating these lesions.

12.
Intern Emerg Med ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864971

RESUMEN

Point-of-care ultrasound (POCUS) is an important tool for clinical diagnosis and decision-making in critical and non-critical scenarios. Dyspnea, chest pain, and shock are conditions susceptible to evaluation with ultrasound considering diagnostic accuracy and clinical impact already proven. There is scarce evidence in diagnosis agreement using ultrasound as an extension of physical examination. We aimed to evaluate ED patients in whom POCUS was performed, to analyze agreement between clinical initial diagnosis using ultrasound images and final diagnosis. Furthermore, we analyze failed diagnosis, inconclusive POCUS exams, and discuss details. A cross-sectional analytical study was conducted on adults who visited the emergency department with any of these three chief complaints: dyspnea, chest pain, and shock. All were evaluated with ultrasound at admission. Agreement between initial diagnosis using POCUS and final definite diagnosis was calculated. Failed diagnosis and inconclusive exams were analyzed. A total of 209 patients were analyzed. Populations: mostly males, mean age 64 years old, hypertensive. Agreement on patients with dyspnea and suspicion of acute decompensated heart failure was 0.98; agreement on chest pain suspicion of non-ST acute coronary syndrome was 0.96; agreement on type of shock was 0.90. Among the population, 12 patients had an inconclusive POCUS exam, and 16 patients had a failed diagnosis. The use of POCUS in the emergency department shows almost perfect agreement when compared with the final diagnosis in individuals experiencing acutely decompensated heart failure, acute coronary syndrome, and shock. Prospective studies are needed to evaluate the impact of this tool on mortality and prognosis when there are diagnostic errors.

13.
Healthcare (Basel) ; 12(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38921281

RESUMEN

The main objective of this study was to analyze the relationship between Geriatric Syndromes (GSs) and in-hospital mortality in adults aged 65 and older admitted to the Emergency Department (ED). The study included 202 Older Adults (OAs) who met the inclusion criteria. We conducted a Comprehensive Geriatric Assessment and collected clinical and demographic data. A univariate analysis was carried out for each of the GSs analyzed. Those variables with p < 0.05 were entered into a multiple logistic regression using the backward stepwise entry method to analyze the independent predictor variables. The average number of GSs per individual was 4.65 (±2.76). Frailty syndrome was the most prevalent (70.2% of patients). Our study found an association between mortality and some GSs, such as frailty (p = 0.042), risk of falls (p = 0.010), delirium, cognitive impairment, dependence, and risk of ulcers (p < 0.001). We found that cognitive impairment (adjusted OR, 6.88; 95% CI, 1.41-33.5; p = 0.017) and dependence (adjusted OR, 7.52; 95% CI, 1.95-29.98; p = 0.003) were independent predictors associated with mortality in our population. It is necessary to develop new care strategies in the ED that respond to the needs of aging societies, including the use of new technologies and personnel with experience in gerontology.

14.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891917

RESUMEN

The European "Green Deal" policies are shifting toward more sustainable and environmentally conscious agricultural practices, reducing the use of chemical fertilizer and pesticides. This implies exploring alternative strategies. One promising alternative to improve plant nutrition and reinforce plant defenses is the use of beneficial microorganisms in the rhizosphere, such as "Plant-growth-promoting rhizobacteria and fungi". Despite the great abundance of iron (Fe) in the Earth's crust, its poor solubility in calcareous soil makes Fe deficiency a major agricultural issue worldwide. Among plant promoting microorganisms, the yeast Debaryomyces hansenii has been very recently incorporated, for its ability to induce morphological and physiological key responses to Fe deficiency in plants, under hydroponic culture conditions. The present work takes it a step further and explores the potential of D. hansenii to improve plant nutrition and stimulate growth in cucumber plants grown in calcareous soil, where ferric chlorosis is common. Additionally, the study examines D. hansenii's ability to induce systemic resistance (ISR) through a comparative relative expression study by qRT-PCR of ethylene (ET) biosynthesis (ACO1), or ET signaling (EIN2 and EIN3), and salicylic acid (SA) biosynthesis (PAL)-related genes. The results mark a significant milestone since D. hansenii not only enhances nutrient uptake and stimulates plant growth and flower development but could also amplify induced systemic resistance (ISR). Although there is still much work ahead, these findings make D. hansenii a promising candidate to be used for sustainable and environmentally friendly integrated crop management.


Asunto(s)
Producción de Cultivos , Fertilizantes , Producción de Cultivos/métodos , Hierro/metabolismo , Cucumis sativus/microbiología , Cucumis sativus/crecimiento & desarrollo , Cucumis sativus/metabolismo , Productos Agrícolas/microbiología , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Deficiencias de Hierro , Regulación de la Expresión Génica de las Plantas , Debaryomyces/metabolismo , Rizosfera , Etilenos/metabolismo , Microbiología del Suelo , Ácido Salicílico/metabolismo
15.
Sci Rep ; 14(1): 9984, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693352

RESUMEN

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.


Asunto(s)
Queratocono , Queratocono/diagnóstico por imagen , Queratocono/diagnóstico , Humanos , Adulto , Femenino , Masculino , Topografía de la Córnea/métodos , Adulto Joven , Aberrometría/métodos , Córnea/diagnóstico por imagen , Córnea/patología , Análisis de Fourier
16.
Data Brief ; 54: 110444, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38708304

RESUMEN

This paper aims to provide a comprehensive and innovative 12-lead electrocardiogram (ECG) dataset tailored to understand the unique needs of professional football players. Other ECG datasets are available but collected from common people, normally with diseases confirmed, while it is well known that ECG characteristics change in athletes and elite players as a result of their intense long-term physical training. This initiative is part of a broader research project employing machine learning (ML) to analyse ECG data in this athlete population and explore them according to the International criteria for ECG interpretation in athletes. The dataset is generated through the establishment of a prospective observational cohort consisting of 54 male football players from La Liga, representing a UEFA Pro-level team. Named the Pro-Football 12-lead Resting Electrocardiogram Database (PF12RED), it comprises 163 10-s ECG recordings, offering a detailed examination of the at-rest heart activity of professional football athletes. Data collection spans five phases over multiple seasons, including the 2018-2019 postseason, the 2019-20 preseason, the 2020-21 preseason, and the 2021-22 preseason. Athletes undergo medical evaluations that include a 10-s resting 12-lead ECG performed with General Electric's USB-CAM 14 module (https://co.services.gehealthcare.com/gehcstorefront/p/900995-002), with data saved using General Electric's CardioSoft V6.73 12SL V21 ECG Software. (https://www.gehealthcare.es/products/cardiosoft-v7) The data collection adheres to ethical principles, with clearance granted by the Autonomous Community of Andalusia Ethics Committee (Spain) under protocol number 1573-N-19 in December 2019. Participants provide informed consent, and data sharing is permitted following anonymization. The study aligns with the Declaration of Helsinki and adheres to the recommendations of the International Committee of Medical Journal Editors (ICMJE). The generated dataset serves as a valuable resource for research in sports cardiology and cardiac health. Its potential for reuse encompasses:1.International Comparison: Enabling cross-regional comparisons of cardiac characteristics among elite football players, enriching international studies.2.ML Model Development: Facilitating the development and refinement of machine learning models for arrhythmia detection, serving as a benchmark dataset.3.Validation of Diagnostic Methods: Allowing the validation of automatic diagnostic methods, contributing to enhanced accuracy in detecting cardiac conditions.4.Research in Sports Cardiology: Supporting future investigations into specific cardiac adaptations in elite athletes and their relation to cardiovascular health.5.Reference for Athlete Protection Policies: Influencing athlete protection policies by providing data on cardiac health and suggesting guidelines for medical assessments.6.Health Professionals Training: Serving as a training resource for health professionals interested in interpreting ECGs in sports contexts.7.Tool and Application Development: Facilitating the development of tools and applications related to the visualization, simulation and analysis of ECG signals in athletes.

19.
Rev Bras Parasitol Vet ; 33(2): e001524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38695451

RESUMEN

Rhipicephalus (Boophilus) microplus is a leading cause of significant economic losses in the livestock industry, and tick populations have developed multiple forms of resistance to acaricides; therefore, the potential of novel natural bioactive compounds that are effective for targeting ticks must be addressed. The aim of this study was to evaluate the acaricidal and anticholinesterase activities of R. aculeata seeds and to identify naturally occurring compounds that potentially inhibit anticholinesterase through in silico docking. The acaricidal activity of the extract of R. aculeata seeds against larval and adult R. microplus ticks was assessed through immersion tests. Inhibition of anticholinesterase activity was measured spectrophotometrically. Extracts of R. aculeata seeds showed activity against larvae and engorged females of R. microplus, and a reduction in the reproductive index were also observed. Rutin, chlorogenic acid, quercetin, and epicatechin exhibited noteworthy interactions with the active site residues of RmAChE. These findings could significantly contribute to the exploration of novel natural products that can potentially inhibit RmAChE and could be used in the development of new acaricides for tick control.


Asunto(s)
Acaricidas , Inhibidores de la Colinesterasa , Extractos Vegetales , Rhipicephalus , Semillas , Animales , Rhipicephalus/efectos de los fármacos , Acaricidas/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Semillas/química , Inhibidores de la Colinesterasa/farmacología , Simulación por Computador , Femenino , Simulación del Acoplamiento Molecular
20.
Genes (Basel) ; 15(4)2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38674430

RESUMEN

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP , Citocromo P-450 CYP3A , Inmunosupresores , Trasplante de Riñón , Polimorfismo de Nucleótido Simple , Tacrolimus , Humanos , Citocromo P-450 CYP3A/genética , Trasplante de Riñón/efectos adversos , Tacrolimus/sangre , Tacrolimus/farmacocinética , Tacrolimus/administración & dosificación , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto , México , Inmunosupresores/farmacocinética , Inmunosupresores/sangre , Inmunosupresores/administración & dosificación , Persona de Mediana Edad , Genotipo , Rechazo de Injerto/genética
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