Profile of plasma microRNAs as a potential biomarker of Wilson's disease.

BACKGROUND: Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. METHODS: We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b-/- mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. RESULTS: In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b-/- mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. CONCLUSIONS: The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.

Patient Safety Incidents in Primary Care: Comparing APEAS-2007 (Spanish Patient Safety Adverse Events Study in Primary Care) with Data from a Health Area in Catalonia (Spain) in 2019.

The initial APEAS study, conducted in June 2007, examined adverse events (AEs) in Spanish Primary Healthcare (PHC). Since then, significant changes have occurred in healthcare systems. To evaluate these changes, a study was conducted in the Camp de Tarragona PHC region (CTPHC) in June 2019. This cross-sectional study aimed to identify AEs in 20 PHC centres in Camp de Tarragona. Data collection used an online questionnaire adapted from APEAS-2007, and a comparative statistical analysis between APEAS-2007 and CTPHC-2019 was performed. The results revealed an increase in nursing notifications and a decrease in notifications from family doctors. Furthermore, fewer AEs were reported overall, particularly in medication-related incidents and healthcare-associated infections, with an increase noted in no-harm incidents. However, AEs related to worsened clinical outcomes, communication issues, care management, and administrative errors increased. Concerning severity, there was a decrease in severe AEs, coupled with an increase in moderate AEs. Despite family doctors perceiving a reduction in medication-related incidents, the overall preventability of AEs remained unchanged. In conclusion, the reporting patterns, nature, and causal factors of AEs in Spanish PHC have evolved over time. While there has been a decrease in medication-related incidents and severe AEs, challenges persist in communication, care management, and clinical outcomes. Although professionals reported reduced severity, the perception of preventability remains an area that requires attention.

Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study / Elevada heterogeneidad en el diagnóstico y tratamiento a largo plazo en la enfermedad de Wilson: resultados de un estudio multicéntrico español

There is uncertainty regarding Wilson's disease (WD) management. Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. Methods: Data on WD patients followed at 32 Spanish hospitals were collected. Results: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. Conclusions: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored. (AU)

Existe incertidumbre con respecto al manejo de la enfermedad de Wilson (EW). Objetivos: Evaluar, en un estudio de cohorte retrospectivo español multicéntrico, si el abordaje de la EW es homogéneo entre los centros. Métodos: Se recogieron datos sobre pacientes con EW seguidos en 32 hospitales españoles. Resultados: Un total de 153 casos, 58% hombres, 20,6 años al diagnóstico, 69,1% presentación hepática, fueron seguidos durante 15,5 años. Se objetivaron resultados discordantes en parámetros de laboratorio no invasivos en el 39,8%. La concentración intrahepática de cobre fue patológica en el 82,4%. Las pruebas genéticas solo se realizaron en el 56,6% con resultados positivos en el 83,9%. Un diagnóstico definitivo de EW (puntuación de Leipzig ≥4) se confirmó retrospectivamente en el 92,5% de los casos. Los agentes quelantes fueron la terapia inicial estándar (75,2%) con modificaciones frecuentes (57%), particularmente hacia zinc de mantenimiento. La normalización enzimática no se logró en un tercio, más comúnmente en el contexto de un cumplimiento deficiente, ausencia de mutaciones genéticas y/o presencia de factores de riesgo cardiometabólicos. Aunque sin alcanzar significación estadística, observamos diferencias entre hombres y mujeres en el número de casos, edad en el momento del diagnóstico y la respuesta bioquímica. Conclusiones: De este estudio multicéntrico que incluye centros de referencia pequeños y grandes se desprende una heterogeneidad significativa en el diagnóstico y manejo de los pacientes con EW. La incorporación de pruebas genéticas ha mejorado el diagnóstico. Las diferencias de sexo deben explorarse más a fondo en estudios futuros. (AU)

Precisión del diagnóstico óptico de pólipos de colon en la práctica clínica / Accuracy for optical diagnosis of colorectal polyps in clinical practice

Antecedentes: el diagnostico óptico consiste en predecir la histopatología de un pólipo a partir de sus características endoscópicas. Sólo es recomendable para pólipos diminutos (≤5 mm) y para predicciones realizadas con alta confianza. Objetivos: evaluar la precisión del diagnóstico óptico en la práctica clínica habitual y valorar si es posible recomendar un intervalo de seguimiento basado en diagnóstico óptico sin esperar el análisis histopatológico. Métodos: estudio prospectivo con pacientes consecutivos > 18 años. Las colonoscopias fueron realizadas por 5 endoscopistas expertos que realizaron previamente un entrenamiento ex-vivo. Se emplearon colonoscopios CF-H180AL y CF-Q180AL y procesadores Exera II (Olympus Medical System, Tokyo, Japan). Se evaluó cada pólipo en tiempo real con luz blanca y narrow band imaging. Se calculó la precisión del diagnóstico óptico (sensibilidad, especificidad, VPN, VPP), así como la concordancia entre la recomendación de seguimiento basada en diagnóstico óptico y en diagnóstico histopatológico. Resultados: se analizaron 311 pólipos de colon < 10 mm (216 diminutos) en 195 pacientes. Precisión del diagnóstico óptico para las predicciones realizadas con alta confianza: pólipos diminutos (sensibilidad 0,59, especificidad 0,92, VPN 0,48); pólipos < 10 mm (sensibilidad 0,73, especificidad 0,88, VPN 0,50). Pudo darse una recomendación de seguimiento basada en diagnóstico óptico a 90 pacientes, coincidiendo con la recomendación tras histopatología según la guía europea en 92,2% y según la guía ESGE en 93,3%. Conclusiones: el diagnóstico óptico permite dar una recomendación de seguimiento tras la colonoscopia. Sin embargo, en este estudio basado en práctica clínica, la precisión del diagnóstico óptico está por debajo de los estándares recomendados (AU)

BACKGROUND: Optical diagnostic involves predicting polyp histopathology from its endoscopic characteristics. It is only recommended for diminutive polyps (≤ 5 mm) and for predictions made with high confidence. OBJECTIVES: To evaluate the accuracy of optical imaging in clinical practice and to assess if optical diagnosis is useful for predicting future colonoscopy surveillance intervals without waiting for histopathological analysis. METHODS: consecutive > 18 years patients were enrolled in this prospective study. Colonoscopies were performed by five expert endoscopists who previously participated in an ex-vivo training. Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II (Olympus Medical System, Tokyo, Japan) processors. Each polyp was characterized in real time using white light and Narrow Band Imaging. Accuracy of optical diagnosis (S, E, NPV, PPV) and correlation between surveillance interval based on optical diagnosis and histopathological analysis were calculated. RESULTS: 311 colon polyps < 10 mm (216 diminutive) in 195 patients were analyzed. Accuracy of optical diagnostics for predictions made with high confidence: Diminutive polyps (sensitivity 0.59, specificity 0.92, NPV 0.48); polyps < 10 mm (sensitivity 0.73, specificity 0.88, NPV 0.50). An optical diagnosis based surveillance recommendation was given to 90 patients. Concordance with histopathology based recommendation was 92.2% according to the European guideline and 93.3% according to the ESGE guideline. CONCLUSIONS: Optical diagnostics can be used to predict future surveillance intervals immediately after colonoscopy. However, in this study, based on clinical practice, the accuracy of optical imaging is below the recommended standards

Factores relacionados con la eficacia del colonoscopio de rigidez variable: resultados de un análisis multivariante / Factors related to the effectiveness of variable stiffness colonoscope: results of a multivariate analysis

Introducción: diversos estudios y dos metaanálisis han demostrado que los colonoscopios con rigidez variable mejoran el porcentaje de intubación cecal. Sin embargo, hay pocos estudios sobre la forma en que deben utilizarse estos colonoscopios. Objetivo: el objetivo del presente estudio fue identificar factores relacionados con el avance del colonoscopio cuando se activa la rigidez variable. Métodos: estudio prospectivo en el que se incluyeron pacientes consecutivos remitidos para colonoscopia. Se utilizó el colonoscopio con rigidez variable (Olympus CF-H180DI/L®). Se realizó análisis univariante y multivariante para identificar los factores relacionados con el avance del colonoscopio tras activar la rigidez variable. Resultados: se analizaron los datos de 260 pacientes. La rigidez variable se utilizó más en segmentos proximales del colon (84 % en colon ascendente y transverso vs. 15.2 % en colon descendente/sigmoide). El índice de masa corporal fue menor en los pacientes en los que el endoscopio avanzó tras activar la rigidez variable que en los que no avanzó (25,9 ± 4,8 vs. 28,3 ± 5,4 kg/m2; p = 0,009). El endoscopio avanzó en menos ocasiones cuando se activó la rigidez en colon ascendente frente a la activación en el resto de segmentos del colon (25 % colon ascendente vs. 64,5 % resto de segmentos; p < 0,05). En el análisis multivariado sólo el segmento del colon en el que se activó la rigidez fue un factor predictivo independiente del avance del endoscopio. Conclusiones: El empleo de la rigidez variable permite el avance del colonoscopio sobre todo cuando se activa en colon transverso, descendente y sigma. Cuando se activa en colon ascendente su eficacia es menor (AU)

Background: Various studies and two meta-analysis have shown that a variable stiffness colonoscope improves cecal intubation rate. However, there are few studies on how this colonoscope should be used. Objective: The aim of this study was to identify factors related to the advancement of the colonoscope when the variable stiffness function is activated. Methods: Prospective study enrolling consecutive patients referred for colonoscopy. The variable stiffness colonoscope (Olympus CF-H180DI/L®) was used. We performed univariate and multivariate analyses of factors associated with the success of the variable stiffness function. Results: After the data inclusion period, 260 patients were analyzed. The variable stiffness function was used most in the proximal colon segments (ascending and transverse colon 85 %; descending/sigmoid colon 15.2 %). The body mass index was lower in patients in whom the endoscope advanced after activating the variable stiffness than those in which it could not be advanced (25.9 ± 4.8 vs. 28.3 ± 5.4 kg/m2, p = 0.009). The endoscope advanced less frequently when the stiffness function was activated in the ascending colon versus activation in other segments of the colon (25 % vs. 64.5 % ascending colon vs. other segments; p < 0.05). In the multivariate analysis, only the colon segment in which the variable stiffness was activated was an independent predictor of advancement of the colonoscope. Conclusions: The variable stiffness function is effective, allowing the colonoscope advancement especially when applied in the transverse colon, descending colon and sigmoid. However, when used in the ascending colon it has a lower effectiveness (AU)

Aneurisma de arteria mesentérica superior / Aneurysm of the superior mesenteric artery

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Púrpura trombótica trombocitopénica asociada a pancreatitis aguda / Thrombotic thrombocytopenic purpura occurring in association with acute pancreatitis

No disponible