Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Genetics of inborn errors of immunity: Diagnostic strategies and new approaches to CNV detection.

BACKGROUND: Genetic diagnosis of inborn errors of immunity (IEI) is complex due to the large number of genes involved and their molecular features. Missense variants have been reported as the most common cause of IEI. However, the frequency of copy number variants (CNVs) may be underestimated since their detection requires specific quantitative techniques. At this point, the use of Next Generation Sequencing (NGS) is acquiring relevance. METHODS: In this article, we present our experience in the genetic diagnosis of IEI based on three diagnostic algorithms that allowed the detection of single nucleotide variants (SNVs) and CNVs. Following this approximation, 703 index cases were evaluated between 2014 and 2021. Sanger sequencing, MLPA, CGH array, breakpoint spanning PCR or a customized NGS-based multigene-targeted panel were performed. RESULTS: A genetic diagnosis was reached in 142 of the 703 index cases (20%), 19 of them presented deletions as causal variants. Deletions were also detected in 5 affected relatives and 16 healthy carriers during the family studies. Additionally, we compile, characterize and present all the CNVs detected by our diagnostic algorithms, representing the largest cohort of deletions related to IEI to date. Furthermore, three bioinformatic tools (LACONv, XHMM, VarSeq™) based on NGS data were evaluated. VarSeq™ was the most sensitive and specific bioinformatic tool; detecting 21/23 (91%) deletions located in captured regions. CONCLUSION: Based on our results, we propose a strategy to guide the molecular diagnosis that can be followed by expert and non-expert centres in the field of IEI.

Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.

Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, ß-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.

Silver Nanowire-Based Transparent Electrodes for V2O5 Thin Films with Electrochromic Properties.

The development of electrochromic systems, known for the modulation of their optical properties under an applied voltage, depends on the replacement of the state-of-the-art ITO (In2O3:Sn) transparent electrode (TE) as well as the improvement of electrochromic films. This study presents an innovative ITO-free electrochromic film architecture utilizing oxide-coated silver nanowire (AgNW) networks as a TE and V2O5 as an electrochromic oxide layer. The TE was prepared by simple spray deposition of AgNWs that allowed for tuning different densities of the network and hence the resistance and transparency of the film. The conformal oxide coating (SnO2 or ZnO) on AgNWs was deposited by atmospheric-pressure spatial atomic layer deposition, an open-air fast and scalable process yielding a highly stable electrode. V2O5 thin films were then deposited by radio frequency magnetron sputtering on the AgNW-based TE. Independent of the oxide's nature, a 20 nm protective layer thickness was insufficient to prevent the deterioration of the AgNW network during V2O5 deposition. On the contrary, crystalline V2O5 films were grown on 30 nm thick ZnO or SnO2-coated AgNWs, exhibiting a typical orange color. Electrochromic characterization demonstrated that only V2O5 films deposited on 30 nm thick SnO2-coated AgNW showed characteristic oxidation-reduction peaks in the Li+-based liquid electrolyte associated with a reversible orange-to-blue color switch for at least 500 cycles. The electrochromic key properties of AgNW/SnO2 (30 nm)/V2O5 films are discussed in terms of structural and morphological changes due to the AgNW network and the nature and thickness of the two protective oxide coatings.

Familial ApoB-specific familial hypobetalipoproteinemia in a patient with non-classical congenital adrenal hyperplasia. / Hipobetalipoproteinemia familiar ApoB específica en una paciente con hiperplasia suprarrenal congénita no clásica.

Familial hypobetalipoproteinaemia is a disorder of lipid metabolism characterized by low levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. ApoB-related familial hypolipoproteinemia is an autosomal condition with a codominance inheritance pattern. Non-classical congenital adrenal hyperplasia is an autosomal recessive disorder due to mutations in the CYP21A2, a gene encoding for the enzyme 21-hydroxylase, which results in an androgen excess production from adrenal source. We here present the case of a 25-year-old woman with NCAH showing decreased levels of total-cholesterol, low-density lipoprotein cholesterol and triglycerides. Her parent had digestive symptoms and severe hepatic steatosis with elevated liver enzymes, as well as decreased levels of total and low-density lipoprotein cholesterol. A genetic-molecular study of the proband identified a mutation in the APOB gene, which allowed a diagnosis of heterozygous ApoB-related hypolipoproteinaemia to be made.

Exploring the degradation of silver nanowire networks under thermal stress by coupling in situ X-ray diffraction and electrical resistance measurements.

The thermal instability of silver nanowires (AgNWs) leads to a significant increase of the electrical resistance of AgNW networks. A better understanding of the relationship between the structural and electrical properties of AgNW networks is primordial for their efficient integration as transparent electrodes (TEs) for next-generation flexible optoelectronics. Herein, we investigate the in situ evolution of the main crystallographic parameters (i.e. integrated intensity, interplanar spacing and peak broadening) of two Ag-specific Bragg peaks, (111) and (200), during a thermal ramp up to 400 °C through in situ X-ray diffraction (XRD) measurements, coupled with in situ electrical resistance measurements on the same AgNW network. First, we assign the (111) and (200) peaks of χ-scans to each five crystallites within AgNWs using a rotation matrix model. Then, we show that the thermal transition of bare AgNW networks occurs within a temperature range of about 25 °C for the electrical properties, while the structural transition spans over 200 °C. The effect of a protective tin oxide coating (SnO2) on AgNW networks is also investigated through this original in situ coupling approach. For SnO2-coated AgNW networks, the key XRD signatures from AgNWs remain constant, since the SnO2 coating prevents Ag atomic surface diffusion, and thus morphological instability (i.e. spheroidization). Moreover, the SnO2 coating does not affect the strain of both (111) and (200) planes. The thermal expansion for bare and SnO2-coated AgNW networks appears very similar to the thermal expansion of bulk Ag. Our findings provide insights into the underlying failure mechanisms of AgNW networks subjected to thermal stress, helping researchers to develop more robust and durable TEs based on metallic nanowire networks.

Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.

BACKGROUND: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated. METHODS: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders). RESULTS: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively. CONCLUSION: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants.

Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia.

High myopia is the most severe and pathological form of myopia. It occurs when the spherical refractive error exceeds -6.00 spherical diopters (SDs) or the axial length (AL) of the eye is greater than 26 mm. This article focuses on early-onset high myopia, an increasingly common condition that affects children under 10 years of age and can lead to other serious ocular pathologies. Through the genetic analysis of 21 families with early-onset high myopia, this study seeks to contribute to a better understanding of the role of genetics in this disease and to propose candidate genes. Whole-exome sequencing studies with a panel of genes known to be involved in the pathology were performed in families with inconclusive results: 3% of the variants found were classified as pathogenic, 6% were likely pathogenic and the remaining 91% were variants of uncertain significance. Most of the families in this study were found to have alterations in several of the proposed genes. This suggests a polygenic inheritance of the pathology due to the cumulative effect of the alterations. Further studies are needed to validate and confirm the role of these alterations in the development of early-onset high myopia and its polygenic inheritance.

Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus.

Keratoconus is a corneal dystrophy that is one of the main causes of corneal transplantation and for which there is currently no effective treatment for all patients. The presentation of this disease in pediatric age is associated with rapid progression, a worse prognosis and, in 15-20% of cases, the need for corneal transplantation. It is a multifactorial disease with genetic variability, which makes its genetic study difficult. Discovering new therapeutic targets is necessary to improve the quality of life of patients. In this manuscript, we present the results of whole-exome sequencing (WES) of 24 pediatric families diagnosed at the University Hospital La Paz (HULP) in Madrid. The results show an oligogenic inheritance of the disease. Genes involved in the structure, function, cell adhesion, development and repair pathways of the cornea are proposed as candidate genes for the disease. Further studies are needed to confirm the involvement of the candidate genes described in this article in the development of pediatric keratoconus.

Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.

Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.

MiR-151a: a robust endogenous control for normalizing small extracellular vesicle cargo in human cancer.

Small extracellular vesicles (sEVs) in the blood of cancer patients contain higher amounts of tumor markers than those identified as free-circulating. miRNAs have significant biomedical relevance due to their high stability and feasible detection. However, there is no reliable endogenous control available to measure sEVs-miRNA content, impairing the acquisition of standardized consistent measurements in cancer liquid biopsy. In this study, we identified three miRNAs from a panel of nine potential normalizers that emerged from a comprehensive analysis comparing the sEV-miRNA profile of six lung and ovarian human cancer cell lines in the absence of or under different conditions. Their relevance as normalizers was tested in 26 additional human cancer cell lines from nine different tumor types undergoing chemotherapy or radiotherapy treatment. The validation cohorts were comprised of 242 prospective plasma and ascitic fluid samples from three different human tumor types. Variability and normalization properties were tested in comparison to miR-16, the most used control to normalize free-circulating miRNAs in plasma. Our results indicate that miR-151a is consistently represented in small extracellular vesicles with minimal variability compared to miR-16, providing a novel normalizer to measure small extracellular vesicle miRNA content that will benefit liquid biopsy in cancer patients.

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital. / [Artículo traducido] Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyse the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: To analyse the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary-level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (management, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analysed by the administration route: Into oral or parenteral. RESULTS: Twenty eight ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing, and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: Limiting the duration of treatments when possible, favouring the implementation of computer prescription order entry, favouring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process, and oral administration over intravenous should be prioritized in order to reduce environmental impact.

Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts.

Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.

Isotope Exchange Raman Spectroscopy (IERS): A Novel Technique to Probe Physicochemical Processes In Situ.

A novel in situ methodology for the direct study of mass-transport properties in oxides with spatial and unprecedented time resolution, based on Raman spectroscopy coupled to isothermal isotope exchanges, is developed. Changes in the isotope concentration, resulting in a Raman frequency shift, can be followed in real time, which is not accessible by conventional methods, enabling complementary insights for the study of ion-transport properties of electrode and electrolyte materials for advanced solid-state electrochemical devices. The proof of concept and strengths of isotope exchange Raman spectroscopy (IERS) is demonstrated by studying the oxygen isotope back-exchange in gadolinium-doped ceria (CGO) thin films. Resulting oxygen self-diffusion and surface exchange coefficients are compared to conventional time-of-flight secondary-ion mass spectrometry (ToF-SIMS) characterization and literature values, showing good agreement, while at the same time providing additional insight, challenging established assumptions. IERS captivates through its rapidity, simple setup, non-destructive nature, cost effectiveness, and versatile fields of application and thus can readily be integrated as new standard tool for in situ and operando characterization in many laboratories worldwide. The applicability of this method is expected to consolidate the understanding of elementary physicochemical processes and impact various emerging fields including solid oxide cells, battery research, and beyond.

Evaluación de las características de la clínica típica del síndrome coronario agudo en mujeres del Área Básica de Salud de Florida Sud, Florida Nord y Pubilla Cases de 2015 a 2019 / Evaluation of the typical clinical characteristics of acute coronary syndrome in women from the basic health area of Florida Sud, Florida Nord and Pubilla Cases from 2015 to 2019

Objetivo: se pretende analizar la adecuación de la clínica previa al diagnóstico de síndrome coronario agudo (SCA) en mujeres de tres Áreas de Salud de Barcelona. El objetivo secundario fue determinar si existe retraso terapéutico en las mujeres analizadas. Métodos: estudio observacional descriptivo transversal sobre mujeres con nuevo diagnóstico de SCA durante 2015-2019 a través de recogida de datos de la historia clínica. Se estimó la adecuación clínica mediante el porcentaje de mujeres que presentaban o no la clínica típica de SCA. Se consideró la presencia de otros síntomas sugestivos y de factores de riesgo cardiovascular. Se tuvieron en cuenta el número acumulado de visitas previas al diagnóstico, el decalaje entre diagnóstico y tratamiento y la actuación en Atención Primaria el mes anterior al diagnóstico. Resultados: se incluyeron 102 mujeres, con una media de edad de 75 años. El 49% presentaron clínica típica (intervalo de confianza [IC] 95%: 39,32-58,72). Los antecedentes más frecuentes fueron hipertensión y dislipemia. De las pacientes analizadas, 11 (10,8%) presentaron debilidad, y, de ellas, 9 (81,8%) presentaron clínica típica, siendo estadísticamente significativo (IC 95%: 4,76-16,80). En el 66,3% de los casos se administró tratamiento inmediato y en el 22,5% se llevó a cabo cateterismo inmediato. Conclusiones: la mitad de las pacientes presentaron clínica típica y ninguno de los síntomas atípicos fue más prevalente. Solo la mitad de las mujeres recibieron tratamiento temprano, con una minoría de tratamientos invasivos. Podría ser beneficioso una mejora del registro de los síntomas en las historias clínicas para mejorar los tiempos en la instauración de tratamiento.(AU)

Aim: to analyze the clinic’s suitability prior to the diagnosis of Acute Coronary Syndrome in women from three health areas of Barcelona. The secondary objective was to determine whether there is a therapeutic delay in the women analyzed. Methods: cross-sectional, descriptive, observational study on women with a new diagnosis of ACS during 2015-2019 by means of data collection from the medical history. Clinical suitability was estimated using the percentage of women who presented or did not present typical symptoms of ACS (dependent variable). The existence of other suggestive symptoms and cardiovascular risk factors (independent variables) was considered. The cumulative number of visits prior to diagnosis, the gap between diagnosis and treatment, and treatment and performance in primary care the month prior to diagnosis (covariables) were taken into account. Results: a total of 102 women with a mean age of 75 years were included; 49% presented typical symptoms. The most common histories were hypertension and dyslipidaemia. Of the patients analyzed, 11 (10.8%) presented weakness, of whom 9 (81.8%) presented typical clinical symptoms. This was statistically significant. Immediate treatment was performed in 66.3% and immediate catheterization was performed in 22.5%. Conclusions: half of the patients presented typical symptoms and none of the atypical symptoms was more prevalent. Only half the women received early treatment with a minority of invasive treatments. Improved recording of symptoms in the clinical histories could be beneficial to improve the times to establish treatment.(AU)

Serie de casos sobre la mortalidad a 30 días tras trombectomía o fibrinólisis. El reto de la dispersión demográfica / Case series on 30-day mortality after thrombectomy or fibrinolysis. The challenge of demographic dispersion

Objetivo: el presente estudio tiene como propósito conocer la supervivencia de la trombectomía o fibrinólisis de pacientes con criterios de código ictus al cabo de 30 días. Además, se propone observar si la dispersión demográfica por ubicación del hospital tiene alguna influencia en dicha relación para el paciente. Método: estudio longitudinal, retrospectivo y observacional. Pacientes dentro del código ictus en la provincia de Ourense (Galicia). Los participantes son 153 pacientes con una media de edad de 76 ± 12 años, de los cuales 83 son mujeres, reclutados durante 17 meses. Las variables a considerar incluyeron la arteria afectada, intervención fibrinólisis/trombectomía, mortalidad al cabo de 30 días, aplicación de angiotomografía computarizada (angio-TC), cambios en la National Institutes Health Stroke Scale (NIHSS) y tiempos en el servicio de urgencias en tres hospitales de la provincia (Ourense, O Barco y Verín). Resultados: el 12,9% de los pacientes fallecieron en los 30 días siguientes a partir del evento. El 54,2% (84 pacientes) fueron sometidos a fibrinólisis; el 19,4%, a trombectomía, y el 26,0% (40 pacientes) fueron tratados mediante intervención combinada (fibrinólisis + trombectomía). El 13,1% de los pacientes bajo fibrinólisis alcanzaron el exitus letalis al cabo de 30 días. El análisis de regresión logística determinó que hacer una trombectomía disminuye la probabilidad de fallecimiento, pero no de forma significativa. Conclusiones: no se encontró una relación significativa entre la aplicación de un tratamiento concreto (trombectomía/fibrinólisis) o su combinación y la tasa de mortalidad de los pacientes al cabo de 30 días.(AU)

Purpose: this study aims to analyze the survival and mortality rate after 30 days in patients with stroke code and fibrinolysis/thrombectomy. In addition, it is proposed to observe whether the demographic dispersion by the hospital’s location has any impact on this relationship for the patient. Method: longitudinal, retrospective and observational study. Patients with stroke code in the province of Ourense, Galicia. Subjects are 153 patients with a mean age of 76±12 years (83 women), recruited over 17 months. The variables to consider included the affected artery, fibrinolysis/thrombectomy intervention, mortality after 30 days, application of computerized tomography angiography, changes in the NIHSS (National Institutes Stroke Scale) and times in the casualty department in three hospitals in the province (Ourense, O Barco and Verín). Results: 12.9% of patients died within 30 days of the event. At least 54.2% of patients (84) received fibrinolysis, 19.4% underwent thrombectomy and at least 40 patients (26.0%) underwent a combined intervention (fibrinolysis + thrombectomy). A total of 13.1% of patients with fibrinolysis reached exitus letalis after 30 days. Logistic analysis determined that performing a thrombectomy reduces the probability of death, but not significantly. Conclusions: no statistically significant relationship was detected between the application of a specific treatment (thrombectomy/fibrinolysis) or its combination with the mortality rate of patients after 30 days. Ourense hospital that is closest to the thrombectomy referral centres shows P<0.005 in regard to mortality.(AU)

Effectiveness of ultrasound screening in right upper quadrant pain: A comparative study in a basic emergency service.

Background and Aims: The use of ultrasound screening is primarily facilitated by point-of-care ultrasound (POCUS) and its integration into healthcare systems is a result of the versatility of this imaging technique. This study intends to compare the accuracy and pertinence of sonographic findings obtained by a sonographer in a Basic Emergency Service (BES) with that of radiologists at referral hospital (RH) in Portugal. Methods: Twenty patients with right upper quadrant (RUQ) pain and suspected cholecystitis or biliary pathology underwent sonography screening using POCUS in the BES. They were then forwarded to the RH where a radiologist performed a conventional ultrasound exam on the same patients. The results of both exams were compared to determine if the findings obtained in the BES were confirmed by the radiologist in the RH. Results: In our sample, 60% of cases were related to biliary pathology, 20% were liver-related, 10% had hepatopancreatic biliary etiology, and 10% had unknown etiology. A strong association between the sonographic findings in the BES and the RH was found in the variables "Sonographic Murphy sign" (V = 0.859; p = 0.001), "Cholelithiasis/Gallbladder sludge" (V = 0.840; p = 0.001), and "Intrahepatic biliary tract dilatation" (V = 0.717; p = 0.006). Adequate measures of agreement between the findings of the radiographer and radiologist were obtained for the "Sonographic Murphy sign" (k = 0.664; p = 0.001) and the presence of "Cholelithiasis/Gallbladder sludge" (k = 0.712; p = 0.000). Conclusion: Major biliary abnormalities were detected in patients with RUQ pain in BES using sonography. The correlation between the sonographic findings obtained by the sonographers at BES and those obtained by radiologists at the RH in Portugal was strong, showing that POCUS screening could be extended to other similar settings; however, more studies are needed.

Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.