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Background and objective: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. Material and Methods: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12 ± 4 weeks post-initiation of evolocumab were reviewed. Results: 60 patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73 m2 (51.7% of patients had eGFR 2]), 50.0% had proteinuria (>300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c ≥160 mg/dL and 29.3% ≥190 mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels 2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study. Resumen: Antecedentes y objetivo: Describir las características clínicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab en las unidades de Nefrología de España. Material y Métodos: Estudio retrospectivo, observacional, y multicéntrico que incluye los pacientes que iniciaron tratamiento con evolocumab (desde febrero 2016 a agosto 2018), en 15 unidades de Nefrología en España. Se revisaron las características demográficas y clínicas de los pacientes, el tratamiento hipolipemiante y la evolución de los perfiles lipídicos entre 24 semanas antes y 12 ± 4 semanas después del inicio de evolocumab. Resultados: Se incluyeron 60 pacientes: 53,3% mujeres, edad media (DE) de 56,9 (12,8) años, 45,0% con hipercolesterolemia familiar (HF) (5,0% homocigota y 40,0% heterocigota), y 65,0% con enfermedad cardiovascular aterosclerótica (ECVA) previa. El filtrado glomerular estimado (FGe) medio fue 62,6 (30,0) ml/min/1,73 m2 (51,7% pacientes con FGe2]), 50,0% proteinuria (>300 mg/g) y 10,0% síndrome nefrótico. Otros factores de riesgo CV fueron: hipertensión (75,0%), diabetes mellitus (25,0%) y hábito tabáquico (21,7%). El 40,0% eran intolerantes a estatinas. Al inicio de evolocumab, el 41,7% tomaban estatinas de alta intensidad, el 18,3% estatinas de moderada intensidad y el 50,0% ezetimiba. Los niveles medios (DE) de c-LDL al inicio de evolocumab fueron de 179,7 (62,9) mg/dL (53,4% pacientes con c-LDL≥160 mg/dL y 29,3% ≥190 mg/dL). Después de 12 semanas del tratamiento con evolocumab se observó una reducción de los niveles de c-LDL del 60,1%. A la semana 12, el 90,0% de pacientes alcanzó niveles c-LDL 2) y prevención secundaria, con niveles de c-LDL muy por encima de los recomendados por las guías. Evolocumab utilizado en práctica clínica, redujo significativamente los niveles de c-LDL en todos los pacientes incluidos en el estudio.

Resumen: Antecedentes y objetivo: Describir las características clínicas de los pacientes tratados con evolocumab, las razones del inicio de la terapia y los efectos del tratamiento en la fase inicial de disponibilidad de evolocumab en las unidades de nefrología de España. Material y métodos: Estudio retrospectivo, observacional y multicéntrico que incluye los pacientes que iniciaron tratamiento con evolocumab (desde febrero de 2016 a agosto de 2018) en 15 unidades de nefrología en España. Se revisaron las características demográficas y clínicas de los pacientes, el tratamiento hipolipemiante y la evolución de los perfiles lipídicos entre 24 semanas antes y 12 ± 4 semanas después del inicio de evolocumab. Resultados: Se incluyeron 60 pacientes: 53,3% mujeres, edad media (DE) de 56,9 (12,8) años, el 45,0% con hipercolesterolemia familiar (HF) (5,0% homocigota y 40,0% heterocigota) y el 65,0% con enfermedad cardiovascular aterosclerótica (ECVA) previa. El filtrado glomerular estimado (FGe) medio fue de 62,6 (30,0) ml/min/1,73 m2 (51,7% pacientes con FGe 2]), el 50,0% con proteinuria (> 300 mg/g) y el 10,0% con síndrome nefrótico. Otros factores de riesgo CV fueron: hipertensión (75,0%), diabetes mellitus (25,0%) y hábito tabáquico (21,7%). El 40,0% eran intolerantes a estatinas. Al inicio de evolocumab, el 41,7% tomaban estatinas de alta intensidad, el 18,3% estatinas de moderada intensidad y el 50,0% ezetimiba. Los niveles medios (DE) de c-LDL al inicio de evolocumab fueron de 179,7 (62,9) mg/dl (53,4% pacientes con c-LDL ≥ 160 mg/dl y 29,3% ≥ 190 mg/dl). Después de 12 semanas del tratamiento con evolocumab se observó una reducción de los niveles de c-LDL del 60,1%. A la semana 12, el 90,0% de los pacientes alcanzó niveles c-LDL 2) y prevención secundaria, con niveles de c-LDL muy por encima de los recomendados por las guías. Evolocumab utilizado en práctica clínica, redujo significativamente los niveles de c-LDL en todos los pacientes incluidos en el estudio. Abstract: Background and objective: To describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain. Material and methods: Retrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12 ± 4 weeks post-initiation of evolocumab were reviewed. Results: Sixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73 m2 (51.7% of patients had eGFR 2]), 50.0% had proteinuria (>300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c≥160 mg/dL and 29.3%≥190 mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels 2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.

At present, designing an RNA sequence that folds into a specific secondary structure is a problem that is not fully solved, due to its exponentially increasing complexity. To address this matter, many computational methods have been developed, but none of them has been able to completely and in an affordable time solve Eterna100, a widely recognized benchmark used to test the performance of RNA inverse folding algorithms. In previous publications we presented the m2dRNAs tool, a Multiobjective Evolutionary Algorithm, and its extension eM2dRNAs, which added a recursive decomposition of the target structure, thus simplifying the problem. At that time they successfully improved the ability to solve the RNA inverse folding problem, but were still unable to complete the Eterna100 benchmark. Here we introduce ES+eM2dRNAs, an improvement of eM2dRNAs that optimizes the decomposition process, as a drawback in its nature was identified.A comparative study of this new tool against its predecessors and other RNA design methods was performed using the two current versions of the Eterna100 benchmark. ES+eM2dRNAs was shown to be the best in all performance indicators considered (number of structures solved, success rate, and total run time). Moreover, it is able to solve two Eterna100 structures for which none of the compared methods had ever found a solution.