Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry.

Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient's journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country.

Versión en español de los criterios STOPP/START 3. Avances en la detección de la prescripción inapropiada de medicamentos en personas mayores / Spanish version of the STOPP/START 3 criteria: Advances in the detection of inappropriate prescribing medication in the older people

Los criterios STOPP/START son criterios explícitos basados en sistemas fisiológicos que resumen la evidencia sobre problemas de prescripción relevantes clínicamente relacionados con el uso de medicamentos potencialmente inapropiados (criterios STOPP) y con potenciales omisiones de prescripción (criterios START). Las dos versiones anteriores de los criterios STOPP/START se publicaron en 2008 y en 2015, y sus versiones en español, en 2009 y en 2015. En 2023 se acaba de publicar la versión3 de dichos criterios. El objetivo de este artículo es presentar la versión traducida al español, así como revisar la utilización y el impacto que ha tenido la versión2 del año 2015 en nuestro idioma. Se realizó una traducción del inglés al español por profesionales expertos y con alto nivel de inglés de la versión3 de los criterios STOPP/START, que incorporan la evidencia publicada desde abril de 2014 hasta marzo de 2022. Además, se hizo una revisión sistemática de las publicaciones que han usado la traducción española de la versión previa (versión2 de 2015) de los criterios STOPP/START. La nueva versión, presentada en este artículo, cuenta con 190 criterios STOPP/START (133 criterios STOPP y 57 criterios START), lo que supone un aumento del 40% en el número de criterios en comparación con la versión anterior. En la revisión se encontraron 37 estudios (21 observacionales, 11 de intervención y 5 de otro tipo) que han usado la versión española en lugar de la internacional. La versión3 en español de los criterios STOPP/START es una lista explícita actualizada de medicamentos potencialmente inapropiados y posibles omisiones en la prescripción que tienen el objetivo de optimizar la medicación y minimizar las reacciones adversas a los medicamentos durante la revisión de la medicación en las personas mayores, en particular aquellas con multimorbilidad y polifarmacia (AU)

The STOPP/START criteria are explicit physiologic systems-based criteria that summarize evidence on clinically relevant prescribing problems related to the use of potentially inappropriate medications (STOPP criteria) and potential prescribing omissions (START criteria). The two previous versions of the STOPP/START criteria were published in 2008 and 2015, and their Spanish versions in 2009 and 2015. Version3 of these criteria has just been published in 2023. The aim of this article is to present the Spanish translated version, and to review the use and impact that version2 of 2015 has had in our language. A translation from English to Spanish was performed by expert professionals with a high level of English of version3 of the STOPP/START criteria, which incorporates the evidence published from April 2014 to March 2022. In addition, a systematic review of publications that have used the Spanish translation of the previous version (version2 of 2015) of the STOPP/START criteria was performed. The new version, presented in this article, has 190 STOPP/START criteria (133 STOPP criteria and 57 START criteria), which is a 40% increase in the number of criteria compared to the previous version. The review found 37 studies (21 observational, 11 interventional and 5 other) that used the Spanish version instead of the international version. The Spanish version 3 of the STOPP/START criteria is an updated explicit list of potentially inappropriate medications and possible omissions in prescribing that aims to optimize medication and minimize adverse drug reactions during medication review in the elderly, particularly those with multimorbidity and polypharmacy (AU)

[Spanish version of the STOPP/START 3 criteria: Advances in the detection of inappropriate prescribing medication in the older people]. / Versión en español de los criterios STOPP/START 3. Avances en la detección de la prescripción inapropiada de medicamentos en personas mayores.

The STOPP/START criteria are explicit physiologic systems-based criteria that summarize evidence on clinically relevant prescribing problems related to the use of potentially inappropriate medications (STOPP criteria) and potential prescribing omissions (START criteria). The two previous versions of the STOPP/START criteria were published in 2008 and 2015, and their Spanish versions in 2009 and 2015. Version3 of these criteria has just been published in 2023. The aim of this article is to present the Spanish translated version, and to review the use and impact that version2 of 2015 has had in our language. A translation from English to Spanish was performed by expert professionals with a high level of English of version3 of the STOPP/START criteria, which incorporates the evidence published from April 2014 to March 2022. In addition, a systematic review of publications that have used the Spanish translation of the previous version (version2 of 2015) of the STOPP/START criteria was performed. The new version, presented in this article, has 190 STOPP/START criteria (133 STOPP criteria and 57 START criteria), which is a 40% increase in the number of criteria compared to the previous version. The review found 37 studies (21 observational, 11 interventional and 5 other) that used the Spanish version instead of the international version. The Spanish version 3 of the STOPP/START criteria is an updated explicit list of potentially inappropriate medications and possible omissions in prescribing that aims to optimize medication and minimize adverse drug reactions during medication review in the elderly, particularly those with multimorbidity and polypharmacy. With this new version, the original criteria are intended to be more widely disseminated within the Spanish-speaking healthcare community. The Spanish version2 of the STOPP/START has been widely used, so we consider that the translation into Spanish has helped to improve pharmacotherapy in older patients with polypharmacy and multimorbidity in our linguistic environment.

Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome.

OBJECTIVE: To describe the clinical characteristics and outcomes in patients with refractory myasthenia gravis (MG) and to determine the effectiveness and side effects of the drugs used for their treatment. METHODS: This observational retrospective cross-sectional multicenter study was based on data from the Spanish MG Registry (NMD-ES). Patients were considered refractory when their MG Foundation of America post-interventional status (MGFA-PIS) was unchanged or worse after corticosteroids and two or more other immunosuppressive agents. Clinical and immunologic characteristics of drug-refractory patients, efficiency and toxicity of drugs used, and outcome (MGFA-PIS) at end of follow-up were studied. RESULTS: We included 990 patients from 15 hospitals. Eighty-four patients (68 of 842 anti-acetylcholine receptor [AChR], 5 of 26 anti-muscle-specific tyrosine kinase [MusK], 10 of 120 seronegative, and 1 of 2 double-seropositive patients) were drug refractory. Drug-refractory patients were more frequently women (p < 0.0001), younger at onset (p < 0.0001), and anti-MuSK positive (p = 0.037). Moreover, they more frequently presented a generalized form of the disease, bulbar symptoms, and life-threatening events (p < 0.0001; p = 0.018; and p = 0.002, respectively) than non-drug-refractory patients. Mean follow-up was 9.8 years (SD 4.5). Twenty-four (50%) refractory patients had side effects to one or more of the drugs. At the end of follow-up, 42.9% of drug-refractory patients (42.6% of anti-AChR, 100% of anti-MuSK, and 10% of seronegative patients) and 79.8% of non-drug-refractory patients (p < 0.0001) achieved remission or had minimal manifestations. Eighty percent of drug-refractory-seronegative patients did not respond to any drug tested. INTERPRETATION: In this study, 8.5% of MG patients were drug-refractory. New more specific drugs are needed to treat drug-refractory MG patients.

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis.

BACKGROUND AND PURPOSE: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG. METHODS: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed. RESULTS: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up. CONCLUSIONS: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.

AIMS: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1. METHODS AND RESULTS: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells. CONCLUSIONS: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations.

Clinical and therapeutic features of myasthenia gravis in adults based on age at onset.

OBJECTIVE: To describe the characteristics of patients with very-late-onset myasthenia gravis (MG). METHODS: This observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late-onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed. RESULTS: A total of 939 patients from 15 hospitals were included: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men (p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti-acetylcholine receptor (anti-AChR) antibodies (p < 0.0001) was higher and fewer patients had thymoma (p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening (p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset (p = 0.002), they required fewer drugs (p < 0.0001) and were less frequently drug-refractory (p < 0.0001). CONCLUSIONS: Patients with MG are primarily ≥65 years of age with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, they achieve a good outcome with fewer immunosuppressants when diagnosed and treated properly.

[The high-sensitivity C-reactive protein level one month after bare-metal coronary stenting may predict late adverse events]. / La PCR-as al mes de implantar un stent coronario metálico puede ser predictora de eventos adversos tardíos.

The significance of the high-sensitivity C-reactive protein (hs-CRP) level in percutaneous coronary interventions (PCIs) is unclear. Troponin-T and hs-CRP levels were measured before PCI, after stenting, and 8 h, 24 h, and 30 days after the procedure in 68 consecutive patients who received bare-metal stents. The study endpoints were death, nonfatal myocardial infarction, and the need for revascularization. The mean follow-up time after PCI was 16.6 months. Patients who experienced an event had higher hs-CRP levels 24 h (P=.05) and 30 days (P< .02) after stenting. The area under the receiver operating characteristic (ROC) curve at 30 days had the highest sensitivity (i.e., 80%) and specificity (i.e., 72%) for predicting an event. The 12-month event-free survival rate (Kaplan-Meier) was greater when the hs-CRP level at 30 days was < or =2.5 mg/L than when it was above this value (P=.04). Consequently, measuring the hs-CRP level 30 days after stenting may be useful for predicting late events.

La PCR-as al mes de implantar un stent coronario metálico puede ser predictora de eventos adversos tardíos / The high-sensitivity C-reactive protein level one month after bare-metal coronary stenting may predict late adverse events

La proteína C reactiva de alta sensibilidad (PCR-as) tiene un valor incierto en el intervencionismo coronario percutáneo (ICP). En 68 pacientes consecutivos tratados con stents metálicos, se determinaron PCR-as y troponina T pre-ICP, post-stent, a las 8 h, a las 24 h y a los 30 días. Los objetivos finales fueron muerte, infarto de miocardio y nueva revascularización. El seguimiento medio post-ICP fue 16,6 meses. Los pacientes con eventos tuvieron PCR-as más alta a las 24 h (p = 0,05) y a los 30 días (p < 0,02). El área bajo la curva ROC de 30 días fue la más sensible (80%) y específica (72%) para predecir eventos. La supervivencia libre de eventos a los 12 meses fue superior cuando la PCR-as a los 30 días era <= 2,5 mg/l que cuando estuvo más elevada (p = 0,04). Por lo tanto, determinar PCR-as 30 días tras el ICP puede ser útil para predecir eventos tardíos

The significance of the high-sensitivity C-reactive protein (hs-CRP) level in percutaneous coronary interventions (PCIs) is unclear. Troponin-T and hs-CRP levels were measured before PCI, after stenting, and 8 h, 24 h, and 30 days after the procedure in 68 consecutive patients who received bare-metal stents. The study endpoints were death, nonfatal myocardial infarction, and the need for revascularization. The mean follow-up time after PCI was 16.6 months. Patients who experienced an event had higher hs-CRP levels 24 h (P=.05) and 30 days (P<.02) after stenting. The area under the receiver operating characteristic (ROC) curve at 30 days had the highest sensitivity (i.e., 80%) and specificity (i.e., 72%) for predicting an event. The 12-month event-free survival rate (Kaplan-Meier) was greater when the hs-CRP level at 30 days was <=2.5 mg/L than when it was above this value (P=.04). Consequently, measuring the hs-CRP level 30 days after stenting may be useful for predicting late events

Síndrome nefrótico y tratamiento con litio / Nephrotic syndrome and lithium therapy

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