Study of the diagnostic efficiency of anti-ZnT8 autoantibodies for type 1 diabetes in pediatric patients.

OBJECTIVE: Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. METHODS: A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. RESULTS: Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. CONCLUSION: The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.

Complete laboratory diagnosis of Insulin Autoimmune Syndrome.

The definition of Insulin autoimmune syndrome includes the presence of high levels of blood insulin and insulin autoantibodies. We encountered a 45-years-old white man with a high insulin serum value that do not fit with the C-peptide result. To discard or to confirm an analytical interference and diagnose a possible Insulin Autoimmune Syndrome we performed the following investigations: dilution linearity test, heterophilic antibody blocking, polyethylene glycol precipitation, measurements with alternative assays, and gel filtration chromatography by size exclusion. The latter technique confirmed that most of the insulin was complexed with a 150-kDa protein, corresponding to immunoglobulin G, identified as insulin autoantibodies. These antibodies were responsible for hypoglycemia attacks in the patient, who had a previous autoimmune disease. This case highlights the importance of carefully analyzing the results and ruling out possible interferences, as well as considering all kinds of pathologies, even if they are infrequent.

Análisis geoestadístico desde el laboratorio clínico en prevención cardiovascular para atención primaria / Geostatistical analysis from the clinical laboratory in cardiovascular prevention for primary care

Introducción y objetivos: Las enfermedades cardiovasculares continúan encabezando la mortalidad en España. Las técnicas de análisis geoestadístico en el laboratorio clínico son herramientas innovadoras que permiten el diseño de nuevas estrategias en prevención primaria de enfermedad cardiovascular. El objetivo fue estudiar la prevalencia y geolocalización de dislipidemias en las áreas sanitarias de estudio para implementar estrategias de prevención en atención primaria. Se llevó a cabo un estudio de cohorte retrospectivo de los niveles de colesterol unido a proteínas de baja densidad, triglicéridos y lipoproteína (a) en los años 2019 y 2020. Además, se realizó un análisis geoestadístico que incluyó la representación en mapas coropléticos y la detección de clústeres de agrupación; para ello, se utilizó la información geográfica en formato de código postal incluida en los datos demográficos de cada analítica. Resultados: Los datos analíticos incluidos en el estudio fueron triglicéridos (n=365.384), colesterol unido a proteínas de baja densidad (n=289.594) y lipoproteína (a) (n=502). Se identificaron las áreas con mayor y menor porcentaje de casos para los puntos de corte establecidos de cLDL> 190mg/dl y TG> 150mg/dl. Se detectaron 2clústeres de agrupación con significación estadística para cLDL> 190mg/dl y un total de 6 clústeres para los valores de TG> 150mg/dl. Conclusiones: La detección de clústeres, así como la representación de mapas coropléticos, pueden ser de gran ayuda en la detección de áreas geográficas que requieran de mayor atención para intervenir en el riesgo cardiovascular.(A)U

Introduction and objectives: Cardiovascular diseases continue to lead the ranking of mortality in Spain. The implementation of geostatistical analysis techniques in the clinical laboratory are innovative tools that allow the design of new strategies in primary prevention of cardiovascular disease. The aim of this study was to study the prevalence and geolocation of severe dyslipidemia in the health areas under study in order to implement prevention strategies in primary care. A retrospective cohort study of low-density protein-bound cholesterol, triglyceride and lipoprotein (a) levels in the years 2019 and 2020 were carried out. In addition, a geostatistical analysis was performed including representation in choropleth maps and the detection of clustering clusters, using geographic information in zip code format included in the demographic data of each analytic. Results: The analytical data included in the study were triglycerides (n=365,384), low density protein-bound cholesterol (n=289,594) and lipoprotein to lipoprotein (a) (n=502). Areas with the highest and lowest percentage of cases were identified for the established cut-off points of LDL-C>190mg/dL and TG>150mg/dL. Two clustering clusters with statistical significance were detected for cLDL>190mg/dL and a total of 6 clusters for TG values>150mg/dL. Conclusions: The detection of clusters, as well as the representation of choropleth maps, can be of great help in detecting geographic areas that require greater attention to intervene and improve cardiovascular risk.(AU)

SmartLab 2.0 in cardiovascular prevention of atherogenic dyslipidemia. / SmartLab 2.0 en prevención cardiovascular de dislipemia aterogénica.

INTRODUCTION: SmartLab 2.0 is an innovative concept of multidisciplinary collaboration between the clinical laboratory and the diabetes day unit that was born with the aim of identifying patients at high cardiovascular risk who require priority attention, such as patients with atherogenic dyslipidemia, in order to create a cardiovascular prevention strategy. OBJECTIVE: Implementation in the Laboratory Information System (LIS) of an automated biochemical algorithm for the identification of patients with atherogenic dyslipidemia in routine analyses and priority referral to the diabetes day unit. MATERIAL AND METHODS: The algorithm designed in the SIL was: HBA1c>9.3 +TG>150mg/dl +HDLc<40mg/dl +LDL/ApoB<1.3. A comment was inserted alerting the requesting physician of the diagnosis of atherogenic dyslipidemia and priority referral was made from the laboratory to the diabetes day unit in the necessary cases. RESULTS: In the 1-year period, a total of 899 patients with HBA1c>7 and atherogenic dyslipidemia criteria were identified. Of these, 203 patients from primary care with HbA1c>9.3 were referred to the diabetes day hospital. CONCLUSIONS: Reinforcement of cardiovascular prevention is necessary at all levels. The clinical laboratory should play a fundamental role in the diagnosis of dyslipidemias. Early detection of patients at high cardiovascular risk is essential and collaboration between the different clinical units is fundamental to guarantee patient safety.

Geostatistical analysis from the clinical laboratory in cardiovascular prevention for primary care. / Análisis geoestadístico desde el laboratorio clínico en prevención cardiovascular para atención primaria.

INTRODUCTION AND OBJECTIVES: Cardiovascular diseases continue to lead the ranking of mortality in Spain. The implementation of geostatistical analysis techniques in the clinical laboratory are innovative tools that allow the design of new strategies in primary prevention of cardiovascular disease. The aim of this study was to study the prevalence and geolocation of severe dyslipidemia in the health areas under study in order to implement prevention strategies in primary care. A retrospective cohort study of low-density protein-bound cholesterol, triglyceride and lipoprotein (a) levels in the years 2019 and 2020 were carried out. In addition, a geostatistical analysis was performed including representation in choropleth maps and the detection of clustering clusters, using geographic information in zip code format included in the demographic data of each analytic. RESULTS: The analytical data included in the study were triglycerides (n=365,384), low density protein-bound cholesterol (n=289,594) and lipoprotein to lipoprotein (a) (n=502). Areas with the highest and lowest percentage of cases were identified for the established cut-off points of LDL-C>190mg/dL and TG>150mg/dL. Two clustering clusters with statistical significance were detected for cLDL>190mg/dL and a total of 6 clusters for TG values>150mg/dL. CONCLUSIONS: The detection of clusters, as well as the representation of choropleth maps, can be of great help in detecting geographic areas that require greater attention to intervene and improve cardiovascular risk.

High sensitivity troponins: A potential biomarkers of cardiovascular risk for primary prevention.

There have been several approaches to building charts for CV risk, all of which have both strengths and limitations. Identifying early organ damage provides relevant information and should be included in risk charts, although the direct relationship with risk is imprecise, variability between operators at the time to assess, and low availability in some healthcare systems, limits its use. Biomarkers, like troponin (cTns) isoforms cTnI and cTnT, a cardiac specific myocyte injury marker, have the great advantage of being relatively reproducible, more readily accessible, and applicable to different populations. New and improved troponin assays have good analytical performance, can measure very low levels of circulating troponin, and have low intra individual variation, below 10 %. Several studies have analyzed the blood levels in healthy subjects and their predictive value for cardiovascular events in observational, prospective and post-hoc studies. All of them offered relevant information and shown that high sensitivity hs-cTnI has a place as an additional clinical marker to add to current charts, and it also reflects sex- and age-dependent differences. Although few more questions need to be answered before recommend cTnI for assessing CV risk in primary prevention, seems to be a potential strong marker to complement CV risk charts.

Laboratory Value-Based Innovation in Heart Failure Improves Patient Health-Related Outcomes.

BACKGROUND: NT-proBNP is emerging as a novel tool for improving management of patients with heart failure (HF). The concept of health-related outcomes as the primary endpoint for therapeutic intervention in chronic disease, such as HF, should be the focal point going forward. METHODS: We conducted a prospective real-world study in heart failure with reduced ejection fraction (HFrEF) patients. The main target was to evaluate the impact on patient's health-related outcomes of a personalized medical follow-up procedure, based on a laboratory model of risk stratification supported by NT-proBNP. One hundred and five consecutive patients admitted to the Hospital Heart-Failure unit were stratified into three groups (low, medium, and high risk) and prospective follow-ups during the 12 months post discharge. RESULTS: It was found that patients under this new approach experienced early and robust improvements in patient health-related outcomes with consistency in most domains which persisted beyond 12 months post follow-up. Improvements in health related quality of life score (HRQLS) was observed over the time of the study. After 6 months we found a significant improvement in HRQLS of 18.2% (from 76.5 ± 22.4 to 95.0 ± 15.7) and 14.4% (from 76.5 ± 22.4 to 96.3 ± 15.9) after 12 months of follow-up (p < 0.001). The highest improvements were found in the symptom severity domain where patients reported an improvement of 22.6% after 6 months and 18.9% after 12 months (p < 0.001). The lowest scores were reported in the physical domain with increase of 11.0% and 4.3% after 6 months and 12 months (p = 0.089). Psychosocial domain and the ability to carry out the activities of normal life showed improvement as well. CONCLUSIONS: Our strategy based on NT-proBNP optimizes HFrEF management and represents a major new approach for clinical laboratories to improve patient health-related outcomes in HFrEF.

Emergency severity level-3 patient flow based on point-of-care testing improves patient outcomes.

BACKGROUND: Overcrowding of the Emergency Department is rapidly becoming a global challenge and a major source of concern for emergency physicians. The desire to improve Emergency Department throughput requires novel approaches to patient flow. MATERIALS AND METHODS: We conducted a prospective and cluster-randomized study, to evaluate the impact in patient outcomes of a new patient flow based on Point-of-Care Testing (POCT). A total of 380 Emergency Severity Level-3 patients were enrolled and studied in two different groups, interventional arm (laboratory analyses performed on POCT analyzers implemented in the Emergency Department) or control arm (central laboratory). The primary outcome was the Emergency Department length of stay. Secondary outcome included the time to first medical intervention, the laboratory turnaround time and the time to disposition decision. Readmission within the 7 days after discharge was also calculated. RESULTS: Length of stay significantly decreased by 88.50 min (from 247.00 to 158.50), time to disposition decision by 89.00 min (from 192.00 to 103.00) and laboratory turnaround time by 67.11 min (from 89.84 to 22.73) in the POCT group. No increase in readmission was found. CONCLUSION: Our strategy based on POCT represents a good approach to optimize patient flow in the Emergency Department and it should be seen as a starting point for further studies focusing on improving throughput.

Comparison of the analytical and clinical performances of two different routine testing protocols for antinuclear antibody screening.

BACKGROUND: The diagnosis of systemic autoimmune rheumatic diseases (SARD) is based on the detection of serum antinuclear antibodies (ANA) for which indirect immunofluorescence (IIF) is the golden standard. New solid-phase immunoassays have been developed to be used alone or in combination with the detection of extractable antinuclear antibodies (ENA) to improve SARD diagnosis. The purpose of this study was to compare the clinical performances of different ANA screening methods alone or in combination with ENA screening methods for SARD diagnosis. METHODS: A total of 323 patients were screened for ANA by IIF, EliA™ CTD Screen, and ELISA methods. Agreements were calculated between the methods. Then, EliA™ CTD Screen positive samples were screened for ENA by line immunoassay (LIA) and fluorescence enzyme immunoassay (FEIA). RESULTS: The diagnostic accuracy of EliA™ CTD Screen (79% sensitivity and 91% specificity) was better than that of ELISA or IIF. The combination of EliA™ CTD plus IIF had the highest sensitivity (93%). ENA determination revealed that Ro52 and Ro60 were the most prevalent specificities. The use of IIF alone was not able of detecting up to 36% of samples positive for Ro52, and 41% for Ro60. CONCLUSIONS: EliA™ CTD Screen has a better diagnostic performance when compared to IIF and ELISA. The combined use of EliA™ CTD Screen and IIF clearly improves the rate and accuracy of SARD diagnosis. The use of EliA™ CTD Screen as first-line screening technique allows the detection of antibodies, which could not be detected by IIF alone.

Contingent prenatal screening for frequent aneuploidies with cell-free fetal DNA analysis.

OBJECTIVE: To analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. MATERIALS AND METHODS: Traditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. RESULTS: In this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. CONCLUSIONS: Our results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.

Development and validation of a laboratory-based risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19.

BACKGROUND: Early identification of patients with COVID-19 who may develop critical illness is of great importance. METHODS: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in a cohort of 154 cases admitted at Valme and Virgen del Rocio University Hospital. RESULTS: A total of 62 (23.5%) patients developed a critical illness during their hospitalization stay, 21 (8.0%) patients needed invasive ventilation, 34 (12.9%) were admitted at the ICU and the overall mortality was of 14.8% (39 cases). 5 variables were included in the final model: age >59.5 years (OR: 3.11;95%CI 1.39-6.97), abnormal CRP results (OR: 5.76;95%CI 2.32-14.30), abnormal lymphocytes count (OR: 3.252;95%CI 1.56-6.77), abnormal CK results (OR: 3.38;95%CI 1.59-7.20) and abnormal creatinine (OR: 3.30;95%CI 1.42-7.68). The AUC of this model was 0.850 with sensitivity of 65% and specificity of 87% and the IDI and NRI were 0.1744 and 0.2785, respectively. The validation indicated a good discrimination for the external population. CONCLUSIONS: Biomarkers add prognostic information in COVID-19 patients. Our risk-score provides an easy to use tool to identify patients who are likely to develop critical illness during their hospital stay.

Biomarkers-based personalized follow-up in chronic heart failure improves patient's outcomes and reduces care associate cost.

BACKGROUND: Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). METHODS: This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient's outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. RESULTS: Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. CONCLUSIONS: A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

Prevalence of severe hypercholesterolemia observed in different hospitals in Andalusia and Ceuta. / Prevalencia de hipercolesterolemias severas observadas en los distintos hospitales de Andalucía y Ceuta.

Severe hypercholesterolaemia is a major cardiovascular risk factor. Early detection and treatment can reduce the incidence of cardiovascular disease. Given the high prevalence of hypercholesterolaemia in Andalusia, the development of a screening strategy for its detection in Primary Care may be an efficient measure. OBJECTIVE: To identify patients in Primary Care with severe hypercholesterolaemia that may increase their cardiovascular risk by reviewing LDL-cholesterol results in computerised laboratory systems. MATERIAL AND METHODS: Observational, retrospective, multi-centre study in 16 hospitals in Andalusia and Ceuta. Anonymous analytical data were acquired from the different laboratory computer systems for the year 2018, and exclusively from Macarena Hospital for the year 2019. RESULTS: From a total of 1,969,035 determinations on≥18 years old, 2,791 patients (0.14%) were detected with LDL-cholesterol>250mg/dl and from a total of 2.327.211 determinations studied in children under 18 years old, 3,804 patients (0.16%) were detected with LDL-cholesterol>135mg/dL. The highest incidence of possible genetic hypercholesterolaemia in adults corresponded to the province of Seville with 23.6 cases/1,000 determinations, while in minors, the highest incidence corresponded to the province of Cadiz with 75 possible cases/1,000 determinations. A geographical triangle of greater prevalence is observed between the provinces of Seville, Huelva and Cadiz. CONCLUSIONS: The development of a screening strategy using a computerised review of LDL-cholesterol in Primary Care detects a large number of subjects with severe hypercholesterolaemia that could benefit from an early intervention.

Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.

Hallazgo casual mediante array de polimorfismo de nucleótido simple. Síndrome de Warkany / Casual finding using single nucleotide polymorphisms arrays: warkany syndrome

Introducción: La trisomía del cromosoma 8, conocida como síndrome de Warkany, es una rara enfermedad genética que cursa con un fenotipo muy variable. Su principal característica clínica es la discapacidad intelectual, facies dismórficas y pliegues plantares profundos. Presentamos el caso de un paciente de 10 años de edad, con facies gargoloides, retraso mental y rigidez en las articulaciones. El estudio inicial del cariotipo, en el que se analizaron 20 metafases, fue normal. Se solicitó array de polimorfismos de nucleótido único (SNPs) al laboratorio. Resultados: Se detectó una ganancia completa del cromosoma 8, que se interpretó como una trisomía 8 en mosaico de aproximadamente un 20%, y que era compatible con la clínica que presentaba el paciente. Discusión: Este caso muestra las limitaciones que tiene el análisis de solo 20 metafases en el cariotipo en pacientes con aneuploidías en mosaico. En estos casos estaría recomendado ampliar el estudio a al menos 30 metafases de cara a detectar mosaicismos en baja proporción

Introduction: Chromosome 8 trisomy, known as Warkany syndrome, is a rare genetic disease that has a very variable phenotype. Its main clinical characteristic is intellectual disability, dysmorphic facies, and deep plantar folds. The case is presented of a 10-year-old patient with gargoyle-like facies, mental retardation, and joint stiffness. The initial study of the karyotype, in which 20 metaphases were analysed, was normal. A single nucleotide polymorphisms (SNPs) array was requested from the laboratory. Results: A complete gain of chromosome 8 was detected, which was interpreted as a mosaic trisomy 8 of approximately 20%, and which was compatible with the clinical presentation of the patient. Discussion: This case shows the limitations of the analysis of only 20 metaphases in the karyotype in patients with mosaic aneuploidies. In these cases it would be recommended to extend the study to at least 30 metaphases in order to detect mosaicisms in low proportion

Recomendaciones para la elaboración de un cuadro de mando integral para la gestión de pruebas en el lugar de asistencia del paciente (POCT). Recomendación (2017) / Recommendations for constructing a balanced scorecard for point-of-care testing (POCT) management. Recommendation (2017)

El avance tecnológico en el campo del diagnóstico clínico ha generado una diversidad de pruebas de laboratorio aplicables en el lugar de asistencia al paciente (POCT), y ha permitido contar con una mayor calidad analítica de los procedimientos implementados. La elaboración de un cuadro de mando integral es una herramienta útil para el éxito en la gestión de un proceso trasversal, complejo e interdisciplinario, como es el de obtener resultados analíticos fiables, transferibles de forma inmediata mediante sistemas POCT. Para la elaboración de un cuadro de mando integral se deben considerar cuatro perspectivas: la de los clientes (pacientes, médicos, grupos de interés), la financiera (inversores privados o públicos), la de los procesos operativos internos (sistemas, procesos) y la de los profesionales (cultura organizativa). El objeto de este documento es establecer recomendaciones para la elaboración de un cuadro de mando integral para gestionar los sistemas POCT disponibles en una institución

Technological development of in vitro diagnostics has led to a diversity of new tests for point-of-care testing (POCT) and at the same time provides quality in the process. Construction of a balanced scorecard is a useful tool for the success in the management of a cross-sectional, complex and interdisciplinary process, as well as to obtain reliable analytical results for immediately use with POCT systems. In constructing a balanced scorecard, four perspectives should be considered: Customer (patients, doctors), Financial (private or public investors), Operating procedures (systems, processes), and Professionals (organisational culture). The aim of this document is to establish the recommendations for the development of an adequate balanced scorecard to manage a point-of-care network in a healthcare system

Noonan syndrome: Severe phenotype and PTPN11 mutations / Síndrome de Noonan: fenotipo grave y mutaciones en el gen PTPN11

Introduction and objective: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. Patients and methods: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. Results: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. Discussion: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations

Introducción y objetivo: El síndrome de Noonan (SN) es un trastorno genético caracterizado por una amplia gama de signos distintivos y problemas de salud. Está causado en el 50% de los casos por mutaciones missense en el gen PTPN11. Se ha postulado que es posible predecir el curso de la enfermedad en función del impacto de las mutaciones en la proteína. Pacientes y métodos: Presentamos 2 casos de fenotipo severo de SN con hydrops fetalis. En ambos casos se realizó la secuenciación del gen PTPN11 en células germinales. Resultados: Se identificaron 2 mutaciones diferentes en dicho gen (p.Gly503Arg y p.Met504Val). Discusión: Estas mutaciones ya han sido identificadas previamente, y cuando se presentan en línea germinal, los pacientes pueden presentar SN clásico, SN con alteraciones malignas o recientemente, p.Gly503Arg se ha observado en un paciente con SN e hydrops fetalis, como los 2 casos que presentamos. Por tanto, estas observaciones muestran, que en pacientes con SN y mutaciones en el gen PTPN11, no es siempre posible determinar la relación genotipo-fenotipo en función del impacto de la mutación en la proteína

Noonan syndrome: Severe phenotype and PTPN11 mutations.

INTRODUCTION AND OBJECTIVE: Noonan syndrome (NS) is a genetic disorder characterized by a wide range of distinctive features and health problems. It caused in 50% of cases by missense mutations in PTPN11 gene. It has been postulated that it is possible to predict the disease course based into the impact of mutations on the protein. PATIENTS AND METHODS: We report two cases of severe NS phenotype including hydrops fetalis. PTPN11 gene was studied in germinal cells of both patients by sequencing. RESULTS: Two different mutations (p.Gly503Arg and p.Met504Val) was detected in PTPN11 gene. DISCUSSION: These mutations have been reported previously, and when they were germinal variants, patients presented classic NS, NS with other malignancies and recently, p.Gly503Arg has been also observed in a patient with severe NS and hydrops fetalis, as our cases. Therefore, these observations shade light on that it is not always possibly to determine the genotype-phenotype relation based into the impact of mutations on the protein in NS patients with PTPN11 mutations.