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Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.
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Protocolos de Quimioterapia Combinada Antineoplásica , DNA Tumoral Circulante , Linfoma Difuso de Grandes Células B , Neoplasia Residual , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Neoplasia Residual/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Biópsia Líquida/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Biomarcadores Tumorais/sangue , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Prognóstico , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Prednisona/uso terapêutico , Prednisona/administração & dosagemRESUMO
The result of the multidisciplinary collaboration of researchers from different areas of knowledge to validate a solar radiation model is presented. The MAPsol is a 3D local-scale adaptive solar radiation model that allows us to estimate direct, diffuse, and reflected irradiance for clear sky conditions. The model includes the adaptation of the mesh to complex orography and albedo, and considers the shadows cast by the terrain and buildings. The surface mesh generation is based on surface refinement, smoothing and parameterization techniques and allows the generation of high-quality adapted meshes with a reasonable number of elements. Another key aspect of the paper is the generation of a high-resolution digital elevation model (DEM). This high-resolution DEM is constructed from LiDAR data, and its resolution is two times more accurate than the publicly available DEMs. The validation process uses direct and global solar irradiance data obtained from pyranometers at the University of Salamanca located in an urban area affected by systematic shading from nearby buildings. This work provides an efficient protocol for studying solar resources, with particular emphasis on areas of complex orography and dense buildings where shadows can potentially make solar energy production facilities less efficient.
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Background and Objectives: Chronic Kidney Disease of uncertain or non-traditional etiology (CKDnT) is a form of chronic kidney disease of undetermined etiology (CKDu) and is not associated with traditional risk factors. The aim of this study was to investigate the association of polymorphisms rs2070744, 4b/a and rs1799983 of the NOS3 gene with CKDnT in Mexican patients. Materials and Methods: We included 105 patients with CKDnT and 90 controls. Genotyping was performed by PCR-RFLP's, genotypic and allelic frequencies were determined and compared between the two groups using χ2 analysis, and differences were expressed as odd ratios with 95% confidence intervals (CI). Values of p < 0.05 were considered statistically significant. Results: Overall, 80% of patients were male. The rs1799983 polymorphism in NOS3 was found to be associated with CKDnT in the Mexican population (p = 0.006) (OR = 0.397; 95% CI, 0.192-0.817) under a dominant model. The genotype frequency was significantly different between the CKDnT and control groups (χ2 = 8.298, p = 0.016). Conclusions: The results of this study indicate that there is an association between the rs2070744 polymorphism and CKDnT in the Mexican population. This polymorphism can play an important role in the pathophysiology of CKDnT whenever there is previous endothelial dysfunction.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Óxido Nítrico Sintase Tipo III/genética , Estudos de Casos e Controles , GenótipoRESUMO
The MYD88 gene has a physiological role in the innate immune system. Somatic mutations in MYD88, including the most common L265P, have been associated with the development of certain types of lymphoma. MYD88L265P is present in more than 90% of patients with Waldenström's macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The absence of MYD88 mutations in WM patients has been associated with a higher risk of transformation into aggressive lymphoma, resistance to certain therapies (BTK inhibitors), and shorter overall survival. The MyD88 signaling pathway has also been used as a target for specific therapies. In this review, we summarize the clinical applications of MYD88 testing in the diagnosis, prognosis, follow-up, and treatment of patients. Although MYD88L265P is not specific to WM, few tumors present a single causative mutation in a recurrent position. The role of the oncogene in the pathogenesis of WM is still unclear, especially considering that the mutation can be found in normal B cells of patients, as recently reported. This may have important implications for early lymphoma detection in healthy elderly individuals and for the treatment response assessment based on a MYD88L265P analysis.
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Mutação , Fator 88 de Diferenciação Mieloide , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Imunoglobulina M/genética , Imunoglobulina M/metabolismo , Linfoma/genética , Linfoma/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/metabolismoRESUMO
The presence of a foreign body in the airway is a potentially life-threatening clinical condition that requires urgent medical attention. We present a case of a 12-year-old boy who presented in the emergency room with a history of an episode of choking after aspiration of a foreign body, followed by severe respiratory distress and subcutaneous emphysema. Chest radiography revealed hyperinflation data, pneumothorax, and subcutaneous emphysema data. The flexible bronchoscope examination showed the presence of an inorganic foreign body impacted on the carina with tracheal lesions and laryngeal edema. It was necessary to perform a tracheostomy for its definitive extraction. The gold standard in the treatment of foreign body aspiration is bronchoscopy; although, in children, the technique adopted continues to be controversial, flexible bronchoscopy can be effective and very useful.
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Corpos Estranhos , Síndrome do Desconforto Respiratório , Enfisema Subcutâneo , Broncoscopia/métodos , Criança , Corpos Estranhos/complicações , Corpos Estranhos/cirurgia , Humanos , Masculino , Enfisema Subcutâneo/complicações , Enfisema Subcutâneo/terapia , TraqueiaRESUMO
The Hodgkin lymphoma (HL) genomic landscape is hardly known due to the scarcity of tumour cells in the tissue. Liquid biopsy employing circulating tumour DNA (ctDNA) can emerge as an alternative tool for non-invasive genotyping. By using a custom next generation sequencing (NGS) panel in combination with unique molecule identifiers, we aimed to identify somatic variants in the ctDNA of 60 HL at diagnosis. A total of 277 variants were detected in 36 of the 49 samples (73·5%) with a good quality ctDNA sample. The median number of variants detected per patient was five (range 1-23) with a median variant allele frequency of 4·2% (0·84-28%). Genotyping revealed somatic variants in the following genes: SOCS1 (28%), IGLL5 (26%), TNFAIP3 (23%), GNA13 (23%), STAT6 (21%) and B2M (19%). Moreover, several poor prognosis features (high LDH, low serum albumin, B-symptoms, IPI ≥ 3 or at an advanced stage) were related to significantly higher amounts of ctDNA. Variant detection in ctDNA by NGS is a feasible approach to depict the genetic features of HL patients at diagnosis. Our data favour the implementation of liquid biopsy genotyping for the routine evaluation of HL patients.
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DNA de Neoplasias/sangue , Técnicas de Genotipagem , Doença de Hodgkin/genética , Biópsia Líquida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Doença de Hodgkin/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
Deletion of the long arm of chromosome 6 (del6q) is the most frequent cytogenetic abnormality in Waldenström macroglobulinaemia (WM), occurring in approximately 50% of patients. Its effect on patient outcome has not been completely established. We used fluorescence in situ hybridisation to analyse the prevalence of del6q in selected CD19+ bone marrow cells of 225 patients with newly diagnosed immunoglobulin M (IgM) monoclonal gammopathies. Del6q was identified in one of 27 (4%) cases of IgM-monoclonal gammopathy of undetermined significance, nine of 105 (9%) of asymptomatic WM (aWM), and 28/93 (30%) of symptomatic WM (sWM), and was associated with adverse prognostic features and higher International Prognostic Scoring System for WM (IPSSWM) score. Asymptomatic patients with del6q ultimately required therapy more often and had a shorter time to transformation (TT) to symptomatic disease (median TT, 30 months vs. 199 months, respectively, P < 0·001). When treatment was required, 6q-deleted patients had shorter progression-free survival (median 20 vs. 47 months, P < 0·001). The presence of del6q translated into shorter overall survival (OS), irrespective of the initial diagnosis, with a median OS of 90 compared with 131 months in non-del6q patients (P = 0·01). In summary, our study shows that del6q in IgM gammopathy is associated with symptomatic disease, need for treatment and poorer clinical outcomes.
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Transformação Celular Neoplásica/genética , Macroglobulinemia de Waldenstrom/genética , Idoso , Doenças Assintomáticas , Células da Medula Óssea/química , Células da Medula Óssea/ultraestrutura , Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Feminino , Humanos , Imunoglobulina M/sangue , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/genética , Paraproteínas/análise , Prognóstico , Intervalo Livre de Progressão , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Rechargeable magnesium batteries attract lots of attention because of their high safety and low cost compared to lithium batteries, and it is needed to develop more efficient electrode materials. Although MgMn2 O4 is a promising material for the positive electrode in Mg rechargeable batteries, it usually exhibits poor cyclability. To improve the electrochemical behavior, we have prepared nanoparticles of MgMn2-y Fey O4 . The XRD results have confirmed that when Mn3+ (Jahn-Teller ion) ions are replaced by Fe3+ (non-Jahn-Teller ion), the resulting MgMn2-y Fey O4 is a cubic phase. The structure and theoretical voltage are theoretically calculated by using the DFT method. The obtained samples have been chemically treated in acid solution for partial demagnesiation, and it is observed that the presence of iron inhibits the deinsertion of Mg through disproportionation and favors the exchange reaction. The electrochemical behavior in non-aqueous magnesium cells has been explored.
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A model for a pumped thermal energy storage system is presented. It is based on a Brayton cycle working successively as a heat pump and a heat engine. All the main irreversibility sources expected in real plants are considered: external losses arising from the heat transfer between the working fluid and the thermal reservoirs, internal losses coming from pressure decays, and losses in the turbomachinery. Temperatures considered for the numerical analysis are adequate for solid thermal reservoirs, such as a packed bed. Special emphasis is paid to the combination of parameters and variables that lead to physically acceptable configurations. Maximum values of efficiencies, including round-trip efficiency, are obtained and analyzed, and optimal design intervals are provided. Round-trip efficiencies of around 0.4, or even larger, are predicted. The analysis indicates that the physical region, where the coupled system can operate, strongly depends on the irreversibility parameters. In this way, maximum values of power output, efficiency, round-trip efficiency, and pumped heat might lay outside the physical region. In that case, the upper values are considered. The sensitivity analysis of these maxima shows that changes in the expander/turbine and the efficiencies of the compressors affect the most with respect to a selected design point. In the case of the expander, these drops are mostly due to a decrease in the area of the physical operation region.
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Recommended genetic categorization of acute myeloid leukaemias (AML) includes a favourable-risk category, but not all these patients have good prognosis. Here, we used next-generation sequencing to evaluate the mutational profile of 166 low-risk AML patients: 30 core-binding factor (CBF)-AMLs, 33 nucleophosmin (NPM1)-AMLs, 4 biCEBPα-AMLs and 101 acute promyelocytic leukaemias (APLs). Functional categories of mutated genes differed among subgroups. NPM1-AMLs showed frequent variations in DNA-methylation genes (DNMT3A, TET2, IDH1/2) (79%), although without prognostic impact. Within this group, splicing-gene mutations were an independent factor for relapse-free (RFS) and overall survival (OS). In CBF-AML, poor independent factors for RFS and OS were mutations in RAS pathway and cohesin genes, respectively. In APL, the mutational profile differed according to the risk groups. High-risk APLs showed a high mutation rate in cell-signalling genes (P = 0·002), highlighting an increased incidence of FLT3 internal tandem duplication (ITD) (65%, P < 0·0001). Remarkably, in low-risk APLs (n = 28), NRAS mutations were strongly correlated with a shorter five-year RFS (25% vs. 100%, P < 0·0001). Overall, a high number of mutations (≥3) was the worst prognostic factor RFS (HR = 2·6, P = 0·003). These results suggest that gene mutations may identify conventional low-risk AML patients with poor prognosis and might be useful for better risk stratification and treatment decisions.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Nucleofosmina , Fatores de RiscoRESUMO
Spontaneous rupture of the spleen is a rare clinical condition that usually presents as a complication of a background pathology and can become a life-threatening condition if it is not diagnosed in time. We present the case of a 15-year-old girl with abdominal pain and clinical data of hypovolemic shock. The simple tomographic study revealed deformation of the splenic architecture and hemoperitoneum. Surgery demonstrated splenic rupture with ptosis spleen and intraperitoneal free blood. The anatomopathological examination showed the presence of splenomegaly and findings suggestive of peliosis. It also highlights the known causes related to spontaneous splenic rupture.
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Hemoperitônio , Ruptura Esplênica , Adolescente , Serviço Hospitalar de Emergência , Feminino , Hemoperitônio/etiologia , Humanos , Ruptura Espontânea/complicações , Ruptura Esplênica/complicaçõesRESUMO
The stability of endoreversible heat engines has been extensively studied in the literature. In this paper, an alternative dynamic equations system was obtained by using restitution forces that bring the system back to the stationary state. The departing point is the assumption that the system has a stationary fixed point, along with a Taylor expansion in the first order of the input/output heat fluxes, without further specifications regarding the properties of the working fluid or the heat device specifications. Specific cases of the Newton and the phenomenological heat transfer laws in a Carnot-like heat engine model were analyzed. It was shown that the evolution of the trajectories toward the stationary state have relevant consequences on the performance of the system. A major role was played by the symmetries/asymmetries of the conductance ratio σhc of the heat transfer law associated with the input/output heat exchanges. Accordingly, three main behaviors were observed: (1) For small σhc values, the thermodynamic trajectories evolved near the endoreversible limit, improving the efficiency and power output values with a decrease in entropy generation; (2) for large σhc values, the thermodynamic trajectories evolved either near the Pareto front or near the endoreversible limit, and in both cases, they improved the efficiency and power values with a decrease in entropy generation; (3) for the symmetric case (σhc=1), the trajectories evolved either with increasing entropy generation tending toward the Pareto front or with a decrease in entropy generation tending toward the endoreversible limit. Moreover, it was shown that the total entropy generation can define a time scale for both the operation cycle time and the relaxation characteristic time.
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OBJECTIVE: To determine the validity of plasma lactate in the emergency department for the early detection of tissue hypoperfusion in septic patients. MATERIALS AND METHODS: Longitudinal descriptive study. Non probabilistic sampling for convenience. Plasma lactate levels were determined in patients admitted to the emergency department with systemic inflammatory response data and clinical suspicion or documented infection. Follow-up was seven days. Complications were considered if the patients presented septic shock, severe sepsis, entry to intensive care or death. RESULTS: Ninety patients were included. The mean age was 57.4±20.31. Fifty five percent (n=49) were women. 25% (n=22) of the patients showed complications. Plasma lactate levels were 1.55mmol/L in uncomplicated patients and 3.72mmol/L for complicated patients (p<0.001). The area under the ROC curve was 0.72 (95% CI, 0.575-0.829). The cutoff point that best described the relationship with the probability of complications was that set at 4.2mmol/L. The variables studied that showed a significant association with the probability of complications were edema (p=0.004), and infections of the respiratory tract (p=0.037). A model that included lactate levels, using as adjustment variables edema and the presence of low respiratory tract infection explained between 0.234 and 0.349 of the dependent variant, correctly classifying 80% of the cases. CONCLUSION: Plasma lactate is useful in emergency departments as a predictive test for the early detection of patients with tissue hypoperfusion that evolve to severe sepsis, septic shock or death.
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Ácido Láctico/sangue , Sepse/sangue , Choque Séptico/sangue , Adulto , Idoso , Biomarcadores/sangue , Diagnóstico Precoce , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Curva ROC , Sepse/complicações , Sepse/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Fatores de TempoRESUMO
The biology of macrochelid mites might offer new venues for the interpretation of the environmental conditions surrounding human death and decomposition. Three human corpses, one from Sweden and two from Spain, have been analysed for the occurrence of Macrochelidae species. Macrocheles muscaedomesticae (Scopoli) females were associated with a corpse that was found in a popular beach area of southeast Spain. Their arrival coincides with the occurrence of one of their major carrier species, the filth fly Fannia scalaris, the activity of which peaks during mid-summer. Macrocheles glaber (Müller) specimens were collected from a corpse in a shallow grave in a forest in Sweden at the end of summer, concurrent with the arrival of beetles attracted by odours from the corpse. Macrocheles perglaber Filipponi and Pegazzano adults were sampled from a corpse found indoors in the rural surroundings of Granada city, south Spain. The phoretic behaviour of this species is similar to that of M. glaber, but it is more specific to Scarabaeidae and Geotrupidae dung beetles, most of which favour human faeces. Macrocheles muscaedomesticae is known from urban and rural areas and poultry farms, M. glaber from outdoors, particularly the countryside, whereas M. perglaber is known from outdoor, rural, and remote, potentially mountainous locations. Macrocheles muscaedomesticae and M. perglaber are reported for the first time from the Iberian Peninsula. This is the first record of M. perglaber from human remains.
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Distribuição Animal , Cadáver , Besouros/fisiologia , Ácaros/fisiologia , Muscidae/fisiologia , Simbiose , Animais , Feminino , Ciências Forenses , Humanos , Espanha , SuéciaAssuntos
Doença de Hodgkin/genética , Carioferinas/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Mutação Puntual , Receptores Citoplasmáticos e Nucleares/genética , Adulto , Distribuição por Idade , Idoso , Feminino , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Linfonodos/química , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Índice de Gravidade de Doença , Distribuição por Sexo , Espanha/epidemiologia , Análise de Sobrevida , Proteína Exportina 1RESUMO
BACKGROUND: Interoperability between health information systems is a fundamental requirement to guarantee the continuity of health care for the population. The Fast Healthcare Interoperability Resource (FHIR) is the standard that enables the design and development of interoperable systems with broad adoption worldwide. However, FHIR training curriculums need an easily administered web-based self-learning platform with modules to create scenarios and questions that the learner answers. This paper proposes a system for teaching FHIR that automatically evaluates the answers, providing the learner with continuous feedback and progress. OBJECTIVE: We are designing and developing a learning management system for creating, applying, deploying, and automatically assessing FHIR web-based courses. METHODS: The system requirements for teaching FHIR were collected through interviews with experts involved in academic and professional FHIR activities (universities and health institutions). The interviews were semistructured, recording and documenting each meeting. In addition, we used an ad hoc instrument to register and analyze all the needs to elicit the requirements. Finally, the information obtained was triangulated with the available evidence. This analysis was carried out with Atlas-ti software. For design purposes, the requirements were divided into functional and nonfunctional. The functional requirements were (1) a test and question manager, (2) an application programming interface (API) to orchestrate components, (3) a test evaluator that automatically evaluates the responses, and (4) a client application for students. Security and usability are essential nonfunctional requirements to design functional and secure interfaces. The software development methodology was based on the traditional spiral model. The end users of the proposed system are (1) the system administrator for all technical aspects of the server, (2) the teacher designing the courses, and (3) the students interested in learning FHIR. RESULTS: The main result described in this work is Huemul, a learning management system for training on FHIR, which includes the following components: (1) Huemul Admin: a web application to create users, tests, and questions and define scores; (2) Huemul API: module for communication between different software components (FHIR server, client, and engine); (3) Huemul Engine: component for answers evaluation to identify differences and validate the content; and (4) Huemul Client: the web application for users to show the test and questions. Huemul was successfully implemented with 416 students associated with the 10 active courses on the platform. In addition, the teachers have created 60 tests and 695 questions. Overall, the 416 students who completed their courses rated Huemul highly. CONCLUSIONS: Huemul is the first platform that allows the creation of courses, tests, and questions that enable the automatic evaluation and feedback of FHIR operations. Huemul has been implemented in multiple FHIR teaching scenarios for health care professionals. Professionals trained on FHIR with Huemul are leading successful national and international initiatives.
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Algoritmos , Aprendizagem , Humanos , Estudantes , Software , Atenção à SaúdeRESUMO
This work provides a novel, low-cost, and effective method to prepare disordered carbon materials for advanced sodium-ion batteries using biomass. A large amount of olive stone waste is yearly produced in the world, and it could be re-used for fine applications other than fuel for heat production. After treatment with sulfuric acid solution and carbonization process, wastes of olive stone are efficiently transformed into optimized carbon electrode material. XRD, XRF and XPS, electron microscopy, and physical gas adsorption are used for the compositional, microstructural, and textural characterization of the carbons. During the synthesis, impurities are removed, C-S links are formed and micropores pores are created. Sulfuric acid acts like S-dopant. The latent pores, or pores closed to nitrogen, can be found using CO2 adsorption, and are very suitable for accommodation for sodium. The results reveal that the reversible capacity is raised from ca. 200â mAh g-1 to ca. 250â mAh g-1 for the carbon obtained through treatment with sulfuric acid. The improved electrochemistry is the result of the s-doping and the porosity.
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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.
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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.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Imunossupressores , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Transplante de Rim/efeitos adversos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Adulto , México , Imunossupressores/farmacocinética , Imunossupressores/sangue , Imunossupressores/administração & dosagem , Pessoa de Meia-Idade , Genótipo , Rejeição de Enxerto/genéticaRESUMO
Despite the fact that mites were used at the dawn of forensic entomology to elucidate the postmortem interval, their use in current cases remains quite low for procedural reasons such as inadequate taxonomic knowledge. A special interest is focused on the phoretic stages of some mite species, because the phoront-host specificity allows us to deduce in many occasions the presence of the carrier (usually Diptera or Coleoptera) although it has not been seen in the sampling performed in situ or in the autopsy room. In this article, we describe two cases where Poecilochirus austroasiaticus Vitzthum (Acari: Parasitidae) was sampled in the autopsy room. In the first case, we could sample the host, Thanatophilus ruficornis (Küster) (Coleoptera: Silphidae), which was still carrying phoretic stages of the mite on the body. That attachment allowed, by observing starvation/feeding periods as a function of the digestive tract filling, the establishment of chronological cycles of phoretic behavior, showing maximum peaks of phoronts during arrival and departure from the corpse and the lowest values in the phase of host feeding. From the sarcosaprophagous fauna, we were able to determine in this case a minimum postmortem interval of 10 days. In the second case, we found no Silphidae at the place where the corpse was found or at the autopsy, but a postmortem interval of 13 days could be established by the high specificity of this interspecific relationship and the departure from the corpse of this family of Coleoptera.