Grado de consecución de los objetivos lipídicos a largo plazo en una cohorte de pacientes con síndrome coronario agudo en práctica clínica real / Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice

Introduction and objectives According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. Methods This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. Results A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88–111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. Conclusions Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7–10 years), especially in patients with recurrent ACS (AU)

Introducción y objetivos Según los recientes estudios epidemiológicos europeos, el grado de control lipídico de los pacientes de muy alto riesgo vascular es subóptimo. En este estudio se han analizado las características epidemiológicas, los factores de riesgo cardiovascular, el perfil lipídico, la recurrencia y el grado de consecución de los objetivos lipídicos a largo plazo, según las Guías ESC/EAS, en una cohorte de pacientes con síndrome coronario agudo (SCA), en condiciones de práctica clínica real. Métodos Estudio de cohorte retrospectivo de los pacientes con diagnóstico de SCA ingresados en la unidad coronaria de un hospital de tercer nivel, entre el 1 de enero de 2012 y el 31 de diciembre de 2015, y seguidos hasta marzo de 2022. Resultados Se estudiaron 826 pacientes. Durante el periodo de seguimiento se observó una mayor prescripción de terapia hipolipemiante combinada, principalmente estatinas de alta y moderada intensidad y ezetimibe. A los 24 meses del SCA, un 33,6% de los pacientes vivos tenían un LDL < 70 mg/dl y en un 9,3% los niveles eran < 55 mg/dl. Al final del seguimiento (101 [88–111] meses), las correspondientes cifras eran del 54,5 y 21,1%. Un 22,1% de los pacientes presentaron un evento coronario recurrente, y solamente un 24,6% de ellos alcanzaron un nivel de LDL < 55 mg/dl. Conclusiones El cumplimiento de los objetivos recomendados por las Guías ESC/EAS en pacientes con SCA, es subóptimo, tanto a los 2 años como a largo plazo (7-10 años) desde el evento, y en especial en los pacientes con SCA recurrente (AU)

Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice.

INTRODUCTION AND OBJECTIVES: According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. METHODS: This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. RESULTS: A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88-111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. CONCLUSIONS: Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7-10 years), especially in patients with recurrent ACS.

The poor accuracy of D-dimer for the diagnosis of prosthetic joint infection but its potential usefulness in early postoperative infections following revision arthroplasty for aseptic loosening.

BACKGROUND: D-dimer was introduced in 2018 as an alternative biomarker for C-reactive protein (CRP) in the diagnostic of prosthetic joint infection (PJI) criteria of the Musculoskeletal Infection Society. We assessed the accuracy of plasma D-dimer for the diagnosis of early, delayed, and late PJI according to Infectious Diseases Society of America (IDSA) criteria, and whether persistently high levels of D-dimer in cases of aseptic loosening (AL) may be predictive of subsequent implant-related infection. METHODS: A prospective study of a consecutive series of 187 revision arthroplasties was performed at a single institution. Septic (n = 39) and aseptic revisions (n = 141) were classified based on IDSA criteria. Preoperative assessment of CRP, erythrocyte sedimentation rate (ESR) and D-dimer was performed. Receiver operating curves were used to determine maximum sensitivity and specificity of the biomarkers. The natural progress of D-dimer for AL cases was followed up either until the date of implant-related infection at any time during the first year or 1 year after revision in patients without failure. Clinical outcomes for those AL cases included infection-related failure that required a new surgery or need for antibiotic suppression. RESULTS: Preoperative D-dimer level was significantly higher in PJI cases than in AL cases (p = 0.000). The optimal threshold of D-dimer for the diagnosis of PJI was 1167 ng/mL. For overall diagnosis of PJI, C-reactive protein (CRP) achieved the highest sensitivity (84.6%), followed by erythrocyte sedimentation rate (ESR) and D-dimer (82% and 71.8%, respectively). Plasma D-dimer sensitivity was lower for all PJI types. When combinations of 2 tests were studied, the combined use of ESR and CRP achieved the best accuracy for all types of PJI (76.9%). 4.25% of AL cases had implant failure due to implant-related infection during the first year after the index revision arthroplasty, only the cases with early failure maintained high D-dimer levels. CONCLUSIONS: Plasma D-dimer did not offer an improvement over the individual or combined diagnosis for any type of PJI according to IDSA criteria. Persistently raised levels of D-dimer after revision arthroplasty in AL cases might be used to effectively diagnose early postoperative infection.

Método sensible para monitorizar la migración de las células madre mesenquimales de la médula ósea en modelos murinos / A sensitive method for monitoring the migration of mesenchymal stem cells from bone marrow in murine models

OBJETIVO: Las células madre mesenquimales (MSCs) son atractivas en la terapia regenerativa de patologías humanas. En los modelos murinos, en los que se trasplantan MSCs humanas, es muy importante poder distinguir el origen de las MSCs identificadas en los órganos de ratones. El objetivo de este estudio fue determinar el rendimiento del análisis basado en PCR de secuencias Alu humanas para detectar ADN humano después de la infusión de células madre de médula ósea humana (hBMSCs) en ratones inmunodeficientes. MATERIAL Y MÉTODO: Las hBMSCs se obtuvieron de la cabeza femoral de pacientes sometidos a cirugía de reemplazo de cadera. Se infundieron 106 hBMSCs por vía intravenosa mediante inyección en el seno retro-orbitario de ratones NOD/SCID. Después se evaluó la presencia de ADN humano en pulmón, hígado y hueso. RESULTADOS: En mezclas de ADN in vitro, el ADN humano se detectó fácilmente con una buena relación logarítmica-lineal. De manera similar, cuando se mezclaron osteoblastos humanos y de ratón, se detectaron fácilmente 1-10 células humanas entre 105 células de ratón. Asimismo, se detectó el ADN humano en los pulmones 1 y 7 días después de las infusiones celulares en ratones NOD/SCID. Sin embargo, el ADN humano se detectó de manera inconsistente en el hígado y los huesos. CONCLUSIÓN: La detección de secuencias Alu es un procedimiento eficaz para detectar ADN humano. Los resultados confirman que la mayoría de las hBMSCs inyectadas por vía intravenosa quedan atrapadas en los pulmones. Por lo tanto, de cara al tratamiento de trastornos esqueléticos, se necesitan procedimientos para aumentar la migración de dichas células al hueso

OBJETIVE: Mesenchymal stem cells (MSCs) are commonly used in regenerative therapy of human diseases. In murine models, in which human MSCs are transplanted, distinguishing the origin of the identified MSCs in the organs of mice is important. The objective of this study was to determine the performance of PCR-based analysis of human Alu sequences to detect human DNA after infusion of human bone marrow stem cells (hBMSCs) in immunodeficient mice. MATERIAL AND METHOD: HBMSCs were obtained from the femoral head of patients undergoing hip replacement surgery. 106 hBMSCs were infused intravenously by injection into the retro-orbital sinus of NOD/SCID mice. The presence of human DNA in lung, liver and bone was then assessed. RESULTS: In in vitro DNA mixtures, human DNA was easily detected with a good logarithmic-linear relationship. Similarly, when human and mouse osteoblasts were mixed, 1-10 cells were easily detected among 105 mouse cells. Likewise, human DNA was detected in the lungs 1 and 7 days after cell infusions in NOD/SCID mice. However, human DNA was inconsistently detected in the liver and bones. CONCLUSION: Detecting Alu sequences is an effective procedure to observe human DNA. The results confirm that most intravenously injected hBMSCs are trapped in the lungs. Thus, for the treatment of skeletal disorders, procedures are needed to increase the migration of these cells to the bone

Influencia del oxígeno a alta concentración en cámara hiperbárica sobre el metabolismo óseo / Influence of high-concentration hyperbaric oxygen therapyon bone metabolism

OBJETIVOS: Conocer las acciones del oxígeno a alta concentración en cámara hiperbárica (CH) sobre la expresión de genes relacionados con el metabolismo óseo en líneas celulares osteoblásticas y hueso trabecular humano. MATERIAL Y MÉTODOS: Se analizó la expresión diferencial de varios genes relacionados con el metabolismo óseo (SOST, RUNX2, MMP14, OPG, HIF-1α y SIRT1) en dos líneas celulares osteoblásticas humanas (Saos y Super-Saos) y en fragmentos de hueso trabecular humano sometidos a una, tres o cinco sesiones de CH (90 minutos, oxígeno 100%; 2,3 atmósferas). En cada experimento se utilizó un control que no recibió CH. RESULTADOS: No encontramos diferencias significativas tras la CH en la expresión de los genes estudiados, ni en las células ni en hueso trabecular. Solo en la línea celular Super-Saos la expresión de OPG tras 5 sesiones de CH descendió 6 veces con respecto a la del grupo control (2-∆Ct de 72; p = 0,01). CONCLUSIONES: El oxígeno a alta concentración en cámara hiperbárica no parece tener influencia en la expresión de genes relacionados con el metabolismo óseo

OBJECTIVES: To learn how high concentration in hyperbaric oxygen therapy (HBO) acts on the expression of genes relatedto bone metabolism in osteoblast cell lines and human trabecular bone. MATERIAL AND METHODS: The differential expression of several genes related to bone metabolism (SOST, RUNX2, MMP14,OPG, HIF‐1α and SIRT1) in two human osteoblastic cell lines (Saos and Super‐Saos) and in human trabecular bone fragments subjected to one, three or five HBO sessions (90 minutes, 100% oxygen; 2.3 atmospheres). In each experiment, acontrol that did not receive HBO was used. RESULTS: We did not find significant differences after HBO in the expression of the genes studied, neither in the cells nor in trabecular bone. Only in the Super‐Saos cell line the expression of OPG after 5 sessions of HBO decreased 6 times with respect to that of the control group (2‐∆CtCt of 72; p = 0.01). CONCLUSIONS: High concentration oxygen in the hyperbaric chamber (HC) does not seem to influence the expression of genes related to bone metabolism

Estudio de la microestructura femoral de pacientes con coxartrosis y con fractura de cadera mediante micro-TAC / Study of the microstructure of femoral patients with hip osteoarthritis and hip fracture by microCT

La disminución de la densidad mineral ósea (DMO), es decir, del volumen de tejido óseo por unidad de volumen del esqueleto, es característica de la osteoporosis, mientras que se ha sugerido que la artrosis se acompaña de un aumento de la DMO a nivel local y sistémico. Para comprobar esta hipótesis analizamos mediante microTAC el hueso trabecular de la cabeza femoral de 10 pacientes con fractura de cadera y 9 con coxartrosis. El análisis no reveló diferencias significativas entre ambos grupos en el volumen de tejido óseo trabecular, ni en los demás parámetros estructurales analizados. Tampoco se encontró una caída significativa del volumen de hueso trabecular con la edad. Esto indica que el hueso de esta región tiene una evolución peculiar. Los mecanismos responsables de ese comportamiento son desconocidos, pero su esclarecimiento podría, quizás, abrir la puerta a nuevos abordajes en el tratamiento de la pérdida de hueso asociada al envejecimiento (AU)

Whereas bone mineral density (BMD) is characteristically low in osteoporosis, it has been postulated that in osteoarthritis BMD is increased. We aimed to check this concept by analyzing bone volumen and structure in the femoral heads of patients with hip fractures (n=10) and with hip osteoarthritis (n=9). Unexpectedly, the analysis of microstructural parameters by microCT did not reveal significant differences between both groups. In addition, we did not find a significant decline in the trabecular bone volume across the age range studied. These results suggest that the evolution of the trabecular bone of the femoral head is different from the age-related decrease of bone mass in other regions of the skeleton. Elucidating the mechanism involved could suggest new approaches to treat the bone loss associated with aging (AU)

Missense polymorphisms of the WNT16 gene are associated with bone mass, hip geometry and fractures.

UNLABELLED: Two missense polymorphisms of WNT16 were associated with hip bone mineral density (BMD), the buckling ratio of the femoral neck, calcaneal ultrasound and hip fractures in individuals under 80 years of age. These results confirm the association of the WNT16 gene with bone mass and osteoporotic fractures. INTRODUCTION: Osteoporosis has a strong genetic component. Wnt ligands stimulate the differentiation of osteoblast precursors and play a major role in skeletal homeostasis. Therefore, the aim of this study was to explore the association of allelic variants of the WNT16 gene with BMD, other structural parameters of bone and osteoporotic hip fractures. METHODS: Six single nucleotide polymorphisms were analysed in 1,083 Caucasian individuals over 49 years of age. RESULTS: Two missense polymorphisms (rs2908004 and rs2707466) were associated with femoral neck BMD, with average differences across genotypes of 35 mg/cm(2) (p = 0.00037 and 0.0015, respectively). Likewise, the polymorphisms were associated with calcaneal quantitative ultrasound parameters (p = 0.00004 and 0.0014, respectively) and the buckling ratio, an index of cortical instability of the femoral neck (p = 0.0007 and 0.0029, respectively). Although there were no significant differences in the genotype frequency distributions between 294 patients with hip fractures and 670 controls, among the subgroup under 80 years of age, TT genotypes were underrepresented in patients with fractures (odds ratio 0.50; CI 0.27-0.94). CONCLUSION: Common missense polymorphisms of the WNT16 gene are associated with BMD at the hip, calcaneal ultrasound and the buckling ratio of the femoral neck, as well as with hip fractures in individuals under 80 years of age. Overall, these results confirm the association of the WNT16 locus with BMD identified in genome-wide association studies and support its role in determining the risk of osteoporotic fractures.

Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study.

OBJECTIVE: Several lines of evidence suggest that estrogens influence the development of osteoarthritis (OA). The aim of this study was to explore the association of two common polymorphisms within the aromatase (CYP19A1) and estrogen receptor (ER) alpha (ESR1) genes with severe OA of the lower limbs. METHODS: The rs1062033 (CYP19A1) and rs2234693 (ESR1) single nucleotide polymorphisms were genotyped in 5528 individuals (3147 patients with severe hip or knee OA, and 2381 controls) from four centres in Spain and the United Kingdom. Gene expression was measured in femoral bone samples from a group of patients. RESULTS: In the global analysis, both polymorphisms were associated with OA, but there was a significant sex interaction. The GG genotype at rs1062033 was associated with an increased risk of knee OA in women [odds ratio (OR) 1.23; P=0.04]. The CC genotype at rs2234693 tended to be associated with reduced OA risk in women (OR 0.76, P=0.028, for knee OA; OR=0.84, P=0.076 for hip OA), but with increased risk of hip OA in men (OR 1.28; P=0.029). Women with unfavourable genotypes at both loci had an OR of 1.61 for knee OA (P=0.006). The rs1062033 genotype associated with higher OA risk was also associated with reduced expression of the aromatase gene in bone. CONCLUSIONS: Common genetic variations of the aromatase and ER genes are associated with the risk of severe OA of the large joints of the lower limb in a sex-specific manner. These results are consistent with the hypothesis that estrogen activity may influence the development of large-joint OA.

Lesiones hepáticas y uso prolongado de anticonceptivos orales / Hepatic lesions and prolonged use of oral contraceptive

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Características funcionales, cognitivas y comorbilidad de ancianos ingresados. (réplica) / Functional, cognitive and comorbidity characteristics of the hospitalized elderly subjects (reply)

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Características funcionales y cognitivas de los ancianos ingresados en un Servicio de Medicina Interna / Functional and cognitive capacity in elderly patients admitted to a general Internal Medicine Service

Fundamento. Analizar las características clínicas, el grado de dependencia física y cognitiva y la cobertura social de los pacientes mayores de 64 años que ingresan en un Servicio de Medicina Interna. Pacientes y métodos. Se han estudiado 105 pacientes (63 mujeres y 42 hombres) mayores de 64 años ingresados en una de las secciones del Servicio de Medicina Interna del Hospital Universitario Marqués de Valdecilla. Resultados. Cincuenta y nueve pacientes eran mayores de 79 años. Las causas más frecuentes que determinaron el ingreso fueron las enfermedades pulmonares, cardíacas y digestivas. El 80% de los pacientes presentaban otros procesos asociados, alcanzándose un índice de comorbilidad de Charlson de 2,7±1,4. El índice de Barthel previo al ingreso fue de 71±35. Más de una tercera parte de los pacientes tenían deterioro cognitivo (MEC <23/35). El 18% de los pacientes recibían algún tipo de ayuda social. Conclusiones. Los ancianos que ingresan en nuestro Servicio de Medicina Interna suelen presentar reagudizaciones de procesos cardiorrespiratorios. Más de la mitad son mayores de 79 años y presentan con relativa frecuencia deterioro cognitivo y funcional. A pesar de ello, la utilización de recursos sociales es todavía escasa

Objectives. To analyze the clinical characteristics, grade of physical and cognitive dependence and social coverage of patients of 64 years who are admitted to an Internal Medicine Service. Design and methods. A total of 105 patients (63 females, 42 males) older than 64 years admitted over 2 months in a General Internal Medicine Unit of a tertiary University Hospital were studied. Results. Fifty nine patients (56%) were 80 years or older. Pulmonary, cardiac, and gastrointestinal problems were the main reasons for admission. A total of 80% of patients had comorbid conditions with a Charlson index of 2.7 ± 1.4. Mean Barthel index before admission was 71 ± 35. More than one third of the patients had cognitive impairment (MMSE < 23/35). Social aid was received by 18% of patients. Conclusions. Patients aged 80 or older with cardiopulmonary disease and a moderate comorbidity grade are frequently admitted to our General Internal Medicine Unit. Physical and cognitive dependence is observed in a significant number of our inpatients, but the uses of social-health services are still low in our area