The importance of genetic counselling for turner syndrome transition.

The healthcare transition (HCT) is the process of planning, monitoring, and adjusting the clinical management from children's care to adult specialists. Although this practice is common for all children, it is especially crucial (and challenging) for those with chronic disorders and genetic conditions that also involve mental health issues, requiring a multidisciplinary approach. In this review, we aim to assess the current status of transition for girls and young women with Turner syndrome (TS) as a model as it is one of the most common sexual chromosomal aneuploidies. We first describe the syndrome highlighting some of the challenges regarding behavioural, neurodevelopmental, and mental health characteristics that must be addressed for a successful HCT. Finally, we emphasize the importance of genetic counselling within multidisciplinary groups for the successful implementation of HCT, especially for girls and women with TS, to facilitate their adaptation and adhesion to the transition process.

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Nurses' preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain.

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Update of cartilaginous tumours according to the WHO classification 2020.

Cartilaginous tumours are a large and heterogeneous group of neoplasms characterised by the presence of a chondroid matrix, with lobular growth and arcuate, ring-like or popcorn-like calcification patterns. MRI shows hyperintensity in T2-weighted sequences and a lobulated or septal relief in postcontrast images. In the WHO 2020 classification, chondral tumours are classified as benign, intermediate or malignant. Despite technological advances, they continue to pose a challenge for both the radiologist and the pathologist, being the main difficulty the differentiation between benign and malignant tumours, which is why they require a multidisciplinary approach. This paper describes the main changes introduced in the 2020 update, describes the imaging characteristics of the main cartilaginous tumours and provides the radiological keys to differentiate between benign and malignant tumours.

Association between myasthenia gravis and Alzheimer's disease. / Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio.

INTRODUCTION: Myasthenia gravis (MG) and Alzheimer's disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu-romuscular junction and in the second, in the central nervous system (CNS). AIM: To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. PATIENTS AND METHODS: We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. RESULTS: We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. CONCLUSION: Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG.

TITLE: Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio.Introducción. La miastenia gravis (MG) y la enfermedad de Alzheimer (EA) son dos de las enfermedades neurológicas en cuya fisiopatología interviene la acetilcolina en distintos niveles. En la primera, la alteración de este neurotransmisor se produce en la unión neuromuscular, y en la segunda, en el sistema nervioso central. Objetivo. Analizar la posible relación entre dichas patologías estudiando la prevalencia y la odds ratio de la EA dentro de los pacientes diagnosticados de MG con respecto a la prevalencia de EA en la población general. Pacientes y métodos. Se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de lenguaje natural a través de la plataforma clínica de inteligencia artificial Savana Manager?. Resultados. Se ha identificado a 970.503 pacientes mayores de 60 años, de los que 1.028 tenían diagnóstico de MG. La proporción de pacientes con diagnóstico de EA dentro de este grupo (4,28%) es mayor que en el resto de la población (2,82%; p = 0,0047), con una odds ratio de 1,54 (intervalo de confianza al 95%: 1,13-2,08; p = 0,0051), sin que se encuentren diferencias significativas en el análisis bivariante del resto de los factores de riesgo para EA más importantes conocidos hasta ahora. Conclusiones. Nuestros resultados sugieren que podría existir un aumento de la prevalencia de EA en pacientes con MG.

Effectiveness and safety of safinamide in the Toledo Movement Disorders Unit. / Efectividad y seguridad de la safinamida en la Unidad de Trastornos de Movimiento de Toledo.

INTRODUCTION: The management of motor fluctuations in Parkinson's disease (PD) can be challenging, and current therapeutic options include the use of monoamine oxidase B inhibitors (MAO-B inhibitors), among others. The aim of this study was to evaluate the effectiveness and safety of safinamide in the clinical practice carried out in the Toledo Movement Disorders Unit. PATIENTS AND METHODS: This is a retrospective study in which data were collected at baseline and at six months from PD patients who were started on safinamide as an add-on therapy with a stable dose of levodopa in line with standard clinical practice. An analysis was performed by subgroups: patients who were given low-dose safinamide and patients who previously received rasagiline. RESULTS: Ninety patients (47 previously received rasagiline) completed the six-month follow-up. A statistically significant decrease in morning akinesia, nocturnal akinesia, wearing off, unpredictable off phenomenon and Unified Parkinson's Disease Rating Scale-III was observed both in those who previously received rasagiline and in those treated with low doses of safinamide. No variation was found in the dyskinesias. The adverse events described were mild, with generalised weakness, dizziness, nausea, headache and alopecia. CONCLUSIONS: Safinamide has been shown to be effective and safe in improving motor fluctuations, motor symptoms and the subjective perception of disease severity in PD patients previously receiving rasagiline and in those receiving low-dose safinamide, all of which is accompanied by a good safety profile.

TITLE: Efectividad y seguridad de la safinamida en la Unidad de Trastornos de Movimiento de Toledo.Introducción. El manejo de las fluctuaciones motoras en la enfermedad de Parkinson (EP) puede suponer un reto, que cuenta entre las diversas opciones terapéuticas actuales con el uso de inhibidores de la monoaminooxidasa B (IMAO-B), entre otros. El objetivo de este estudio fue evaluar la efectividad y seguridad de la safinamida en la práctica clínica de la Unidad de Trastornos de Movimiento de Toledo. Pacientes y métodos. Es un estudio retrospectivo en el que se registraron datos en una visita inicial y a los seis meses de pacientes con EP en los que se inició tratamiento con safinamida como terapia adicional con una dosis estable de levodopa según la práctica clínica habitual. Se realizó un análisis por subgrupos: pacientes que recibieron safinamida en dosis bajas y pacientes que recibieron previamente rasagilina. Resultados. Completaron los seis meses de seguimiento 90 pacientes (47 recibieron previamente rasagilina). Tanto en los pacientes que recibieron rasagilina previa como en los tratados con dosis bajas de safinamida se observó una disminución estadísticamente significativa de la acinesia matutina, la acinesia nocturna, el wearing off, el fenómeno off impredecible y la Unified Parkinson's Disease Rating Scale-III. No hubo variación en las discinesias. Los acontecimientos adversos descritos fueron leves, y se describieron sensación de debilidad generalizada, mareo, náuseas, cefalea y alopecia. Conclusiones. La safinamida ha demostrado ser eficaz y segura en la mejoría de fluctuaciones motoras, los síntomas motores y la percepción subjetiva de la gravedad de la enfermedad tanto en pacientes con EP que recibieron previamente rasagilina como en los que recibieron safinamida en dosis bajas, todo ello acompañado de un buen perfil de seguridad.

Reverse total shoulder arthroplasty for proximal humerus fractures: Primary or delayed after failed treatment?

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has recently become an option for the treatment of proximal humerus fractures (PHFs) or as a salvage procedure after failure of another treatment. The purpose of this study was to compare primary RTSA with delayed RTSA in the treatment of displaced PHFs. STUDY DESIGN & METHODS: A retrospective cohort study was conducted on patients with PHFs who were treated between May 2013 and December 2021 with primary or delayed RTSA after failure of conservative treatment or osteosynthesis. Clinical data were withdrawn from our local computerized database. Complications, active range of motion, as well as the functional outcome were recorded at the end of the follow-up period. Differences between clinical outcomes were analyzed using a logistic regression analysis. RESULTS: A total of 70 individuals were included in this study (41 primary RTSA and 29 delayed RTSA). The mean of follow-up time was of 112 and 60 months, respectively. There were no differences between groups regarding fracture type according Neer Classification, ASA score or the presence of complications. Q-DASH and Oxford Shoulder scores were significantly better when patients underwent a primary RTSA (49.8 vs 31.4, p = 0.006 and 37.2 vs 27.5, p = 0.004 respectively). In addition, primary RTSA achieved more degrees of flexion and abduction than delayed RTSA (96.8 vs 72.9, p < 0.001 and 94.1 vs 69.3, p < 0.001 respectively). CONCLUSION: Primary RTSA for PHFs achieved better functional outcomes and a wider range of motion when compared with delayed RTSA. However, primary and delayed RTSA have similar complication and reintervention rates. LEVEL OF CLINICAL EVIDENCE: 3.

[Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia]. / Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.

TITLE: Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.

Color prediction of layered dental resin composites with varying thickness.

OBJECTIVE: The aim of this study was to assess the accuracy of a Principal Components Analysis (PCA)-based method for reflectance reconstruction and color estimation of layered dental resin-based composites with different thicknesses. METHOD: Bi-layered samples of different clinically relevant thicknesses were created using shades of VITAPAN Excell (VE), VITAPAN Dentine (VD) and VITA Physiodens (VP), combined with their corresponding enamel shades. Spectral reflectance of all samples was measured over a black background using a non-contact spectroradiometer with CIE 45∘∕0∘ geometry. Two different PCA-based models, built from two different configurations of known samples, were proposed to reconstruct the spectral data and color of unknown layered samples. Root Mean Square Error (RMSE), Goodness of Fit (GFC), as well as ΔE00 with corresponding 50:50% acceptability and perceptibly thresholds (AT and PT) were used as performance assessment. RESULTS: The 5-samples training set approach provided an average RMSE < 0.015 and GFC > 0.999 when measured and predicted spectral reflectances were compared, while for the 9-samples training set, RMSE < 0.0098 and GFC > 0.9999 were obtained. The overall mean color differences obtained with the 5-samples training set approach were ΔE00 = 0.99 (AT% = 96.25% and PT% = 32.50%), while using the 9-samples training set resulted in lower overall mean color differences: ΔE00 = 0.50 (AT% = 99.22% and PT% = 83.87%). SIGNIFICANCE: Within the framework of this study, the two proposed PCA-based configurations allow the prediction of the spectral reflectance of layered dental resin-based composites of different shades and thicknesses, with a high degree of accuracy.

Bilateral neurosensory retinal detachment secondary to tadalafil treatment.

A 53-year-old male with no systemic disorders, other than controlled arterial hypertension, presented with asymptomatic, bilateral neurosensory retinal detachment (NRD) detected during a routine revision. The patient reported the use of tadalafil (a phosphodiesterase-5 inhibitor [PDE5I]) for erectile dysfunction. Following suspension of the drug, subretinal fluid reabsorption was confirmed, with the persistence of chronic alterations in the optical coherence tomography (OCT) and the visual field. PDE5Is have ocular side effects, including exudative retinal detachment. Although no direct causal relationship has been confirmed, PDE5 inhibition at chorioretinal level produces vasodilatation, increased choroid hydrostatic pressure, and exudation into the subretinal space. In cases of NRD, a thorough assessment of the drug treatment history is crucial. Patients who use PDE5I drugs should be alerted to their potential ocular side effects.

Efficacy of early use of remdesivir: a systematic review of subgroup analysis.

OBJECTIVE: A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19. METHODS: A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability. RESULTS: A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution. CONCLUSIONS: We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.

Microbiota composition and intestinal integrity remain unaltered after the inclusion of hydrolysed Nannochloropsis gaditana in Sparus aurata diet.

The use of lysed microalgae in the diet of carnivorous fish can increase the bioavailability of proteins and bioactive compounds, such as unsaturated fatty acids or vitamins in the digestive tract. These are essential molecules for the proper physiological development of fish in aquaculture. However, some antinutritional components and other undesirable molecules can be released from an excess of microalgae supplied, compromising the integrity of the intestine. The inclusion of small amounts of hydrolized microalgae in the fish diet can be a good strategy to avoid negative effects, improving the availability of beneficial compounds. Nannochloropsis gaditana is an interesting microalgae as it contains nutraceuticals. Previous studies reported beneficial effects after its inclusion in the diet of Sparus aurata, a widely cultured species in Europe and in all Mediterranean countries. However, administration of raw microalgae can produce intestinal inflammation, increased intestinal permeability, bacterial translocation and disturbance of digestion and absorption processes. The aim of this study was to evaluate changes in the intestinal microbiota and barrier stability of S. aurata fed with low inclusion (5%) hydrolysed N. gaditana. Intestinal microbiota was analyzed using Illumina MiSeq technology and libraries were constructed using variable regions V3-V4 of 16S rDNA molecules. Analysis were based in the identification, quantification and comparison of sequences. The predictive intestinal microbial functionality was analyzed with PICRUSt software. The results determined that the intestinal microbiota bacterial composition and the predictive intestinal microbiota functionality did not change statistically after the inclusion of N. gaditana on the diet. The study of gene expression showed that genes involved in intestinal permeability and integrity were not altered in fish treated with the experimental diet. The potential functionality and bacterial taxonomic composition of the intestinal microbiota, and the expression of integrity and permeability genes in the intestine of the carnivorous fish S. aurata were not affected by the inclusion of hydrolysed 5% N. gaditana microalgae.