ABSTRACT Introduction and objectives: Coronary lesions with stent overlapping are associated with higher neointimal proliferation that leads to more restenosis. Furthermore, the tapering of coronary ...arteries is a major challenge when treating long coronary lesions. This study attempted to assess the safety and clinical level of performance of long nontapered sirolimus-eluting coronary stent systems (> 36 mm) to treat long and diffused de novo coronary lesions in real-world scenarios. Methods: This was a prospective, non-randomized, multicentre study that included 696 consecutive patients treated with the long nontapered BioMime sirolimus-eluting coronary stent system in long and diffused de novo coronary lesions. The safety endpoint was major adverse cardiovascular events defined as a composite of cardiac death, myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, and major bleeding at the 12-month follow-up. Results: Of a total of 696 patients, 38.79% were diabetic. The mean age of all the patients was 64.6 ± 14 years, and 80% were males. The indication for revascularization was acute coronary syndrome in 63.1%. A total of 899 lesions were identified out of which 742 were successfully treated with long BioMime stents (37 mm, 40 mm, 44 mm, and 48 mm). The cumulative incidence of major adverse cardiovascular events was 8.1% at the 12-month follow-up including cardiac death (2.09%), myocardial infarction (1.34%), and total stent thrombosis (0.5%). Conclusions: This study confirms the safety and good performance of long nontapered BioMime coronary stents to treat de novo coronary stenosis. Therefore, it can be considered a safe and effective treatment for long and diffused de novo coronary lesions in the routine clinical practice.
Introduction and objectives: Coronary lesions with stent overlapping are associated with higher neointimal proliferation that leads to more restenosis. Furthermore, the tapering of coronary arteries ...is a major challenge when treating long coronary lesions. This study attempted to assess the safety and clinical level of performance of long nontapered sirolimus-eluting coronary stent systems (> 36 mm) to treat long and diffused de novo coronary lesions in real-world scenarios.
Methods: This was a prospective, non-randomized, multicentre study that included 696 consecutive patients treated with the long nontapered BioMime sirolimus-eluting coronary stent system in long and diffused de novo coronary lesions. The safety endpoint was major adverse cardiovascular events defined as a composite of cardiac death, myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, and major bleeding at the 12-month follow-up.
Results: Of a total of 696 patients, 38.79% were diabetic. The mean age of all the patients was 64.6 ± 14 years, and 80% were males. The indication for revascularization was acute coronary syndrome in 63.1%. A total of 899 lesions were identified out of which 742 were successfully treated with long BioMime stents (37 mm, 40 mm, 44 mm, and 48 mm). The cumulative incidence of major adverse cardiovascular events was 8.1% at the 12-month follow-up including cardiac death (2.09%), myocardial infarction (1.34%), and total stent thrombosis (0.5%).
Conclusions: This study confirms the safety and good performance of long nontapered BioMime coronary stents to treat de novo coronary stenosis. Therefore, it can be considered a safe and effective treatment for long and diffused de novo coronary lesions in the routine clinical practice.
Introducción y objetivos: Las lesiones coronarias largas y difusas, cuando se tratan percutáneamente, requieren a menudo superposición de los stents, que se asocia a una mayor tasa de reestenosis. Por otro lado, el adelgazamiento progresivo de las arterias dificulta el tratamiento de las lesiones largas. En este estudio se analizan la seguridad y la eficacia clínica de los stents liberadores de sirolimus largos no cónicos (> 36 mm) para el tratamiento de lesiones largas de novo en un escenario real.
Métodos: Estudio prospectivo, no aleatorizado, multicéntrico, con 696 pacientes consecutivos con implantación de stent BioMime largo no cónico para el tratamiento de lesiones coronarias de novo largas y difusas. El criterio de valoración de seguridad fueron los eventos adversos cardiovasculares mayores en el seguimiento, definidos como la combinación de muerte cardiaca, infarto de miocardio, necesidad de nueva revascularización en la misma lesión guiada por la clínica, trombosis del stent o hemorragia mayor a los 12 meses.
Resultados: De los 696 pacientes incluidos, el 38,79% eran diabéticos. La edad media fue de 64,6 ± 14 años y el 80% eran varones. La indicación de revascularización fue un síndrome coronario agudo en el 63,1%. Se identificaron 899 lesiones, de las que 742 se trataron con éxito con stents BioMime (37-40-44-48 mm). La incidencia acumulada de eventos adversos cardiovasculares mayores fue del 8,1% a los 12 meses, con un 2,09% de muertes de causa cardiaca, un 1,34% de infartos de miocardio y un 0,5% de trombosis del stent.
Conclusiones: El presente estudio confirma la seguridad y el buen perfil clínico a 12 meses del stent BioMime largo no cónico para el tratamiento de lesiones coronarias de novo largas y difusas, por lo que debe considerarse un tratamiento seguro y eficaz para este tipo de lesiones en la práctica clínica habitual.
Summary
Polyphosphate (polyP) is a linear chain of up to hundreds of inorganic phosphate residues that is necessary for many physiological functions in all living organisms. In some bacteria, polyP ...supplies material to molecules such as DNA, thus playing an important role in biosynthetic processes in prokaryotes. In the present study, we set out to gain further insight into the role of polyP in eukaryotic cells. We observed that polyP amounts are cyclically regulated in Saccharomyces cerevisiae, and those mutants that cannot synthesise (vtc4Δ) or hydrolyse polyP (ppn1Δ, ppx1Δ) present impaired cell cycle progression. Further analysis revealed that polyP mutants show delayed nucleotide production and increased genomic instability. Based on these findings, we concluded that polyP not only maintains intracellular phosphate concentrations in response to fluctuations in extracellular phosphate levels, but also muffles internal cyclic phosphate fluctuations, such as those produced by the sudden demand of phosphate to synthetize deoxynucleotides just before and during DNA duplication. We propose that the presence of polyP in eukaryotic cells is required for the timely and accurate duplication of DNA.
The phosphate concentration in cells remains constant through the cell cycle, although there are stages where a higher demand of phosphate is required (DNA replication). The faithful duplication of genomes is reliant upon a constant supply of deoxynucleotide triphosphates (dNTP). Here, we show that the degradation of polyphosphate is involved in buffering the cyclical intracellular variations in the phosphate concentration and thus is an important process in sustaining dNTP synthesis and maintaining correct cell proliferation.
The upward trend in energy prices makes it necessary to find new ways to provide electricity to end consumers. The cooperation between different self-consumption facilities that form an energy ...community based on networked microgrids can be a more efficient way of managing the available renewable resources. However, the complexity of its associated control problem is bringing unresolved challenges from the point of view of its formulation. The optimization of energy exchanges among microgrids in the day-ahead electricity market needs to generate an optimal profile for the purchase and sale of energy with the main grid, being charged for any deviation from the schedule proposed in the regulation service market. Microgrids based on renewable generation are systems subject to inherited uncertainties in their energy forecast, whose interconnection generates a distributed control problem of stochastic systems. Microgrids are systems of subsystems that can integrate various components, such as hybrid energy storage systems (ESS), generating multiple terms to be included in the associated cost function for its optimization. In this work, the problem of solving complex distributed stochastic systems in the Mixed Logic Dynamic (MLD) framework is addressed, generating a tractable formulation to generate deterministic values for both exchange and output variables in interconnected systems subject to uncertainties using hybrid, stochastic and distributed Model Predictive Control (MPC) techniques.
Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against ...SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD.
e16617 Background: Diverse trials using immune checkpoint inhibitors (ICI) in the adjuvant setting in urothelial carcinoma (UC) or in the peri-operative setting in renal cell carcinoma (RCC) have ...been recently published. However, conflicting results have been noted. Methods: A meta-analysis of the randomized phase 3 trials of peri-operative treatment with anti-PD-1/PD-L1 agents or anti-PD1/antiCTL4 in combination in RCC or UC was conducted. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). Secondary outcomes of interest were the proportion of grade 3-4 adverse events (AE) according to CTCAE 5.0. Subgroup analyses were performed according to clinically relevant characteristics. Statistical heterogeneity assumption was evaluated by the χ²-based Cochran’s Q test and quantified with the I² statistic. All statistical analyses were performed using RevMan® (version 5.4, The Cochrane Collaboration, 2020). Results: Published results of 7 phase 3 trials were included, involving 4232 RCC patients and 2220 UC patients. 3425 patients received ICI (anti-PD1: 2018 patients; anti-PD-L1 796 patients, antiPD1/anti-CTLA4 611 patients) while 3027 received no active treatment (1861 placebo, 1166 observation). ICI did not show to increase DFS (Hazard ratio (HR) 0.85 95% CI 0.72 - 1.00, p 0.05) or OS (HR 0.77 95% CI 0.49 - 1.20, p 0.25) in RCC patients. ICI showed an increase in DFS (HR 0.76 95% CI 0.65 - 0.90, p 0.002) but not in OS (HR 0.91 95% CI 0.76 - 1.09, p 0.30) in UC patients. High-grade AEs were approximately 2 times more frequent in the immunotherapy arm in RCC (OR 2.48 95% CI 1.55 - 3.96, p < 0.001) and UC (OR 1.82 95% CI 1.27 - 2.60, p 0.001) patients compared to placebo or observation. Subgroup analyses showed statistically significant differences among selected subgroups. In RCC patients, an effect favoring experimental arm in patients with sarcomatoid differentiation (HR 0.57 95% CI 0.40 - 0.82, p 0.002) and PD-L1 positive tumors (HR 0.73 95% CI 0.61 - 0.89, p 0.001) was noted. In UC patients, a statistically significant difference was noted in patient that had received neoadjuvant chemotherapy (HR 0.69 95% CI 0.52 - 0.90, p 0.006) and, interestingly, in PD-L1 negative patients (HR 0.78 95% CI 0.64 - 0.94, p 0.009). PD-L1 positivity was not associated with a significant benefit in DFS (HR 0.74 95% CI 0.51 - 1.08, p 0.12). Upper tract showed a trend for inferior outcomes with adjuvant ICI (HR 1.19 95% CI0.86 - 1.65, p 0.29). Conclusions: The introduction of anti-PD-(L)1 +/- anti-CTLA-4 agents in the adjuvant setting of RCC and UC might benefit some patients, although no currently available biomarker is available to select them. Concerns may also arise about a potential increase in toxicity. Longer follow-up of the conducted studies and data from studies pending publication is needed to establish a potential benefit in long-term survival.
•A new function for the polyphosphate (polyP) is proposed.•polyP provide phosphate for the extra demand of dNTPs needed for DNA damage repair.•This function is conserved in human dermal fibroblast.
...Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention.
Conocer mejor las variables clínicas, funcionales y analíticas que se asocian al síndrome confusional agudo (SCA) en urgencias y la evolución de las mismas con el fin de obtener una mejora en el ...abordaje terapéutico del paciente anciano previniendo así la morbimortalidad en este tipo de pacientes.
Se trata de un estudio descriptivo prospectivo de SCA en urgencias.
Hospital General Universitario de Ciudad Real.
Se incluyó, en el intervalo de las 24 h siguientes al ingreso en el Servicio de Geriatría, a todos los pacientes procedentes del Servicio de Urgencias con diagnóstico de SCA.
Se realizó un análisis de las variables del conjunto de datos (variables sociodemográficas y clínicas), calculando tablas de frecuencias para variables de tipo cualitativo y estadísticos descriptivos para las variables cuantitativas. Posteriormente, se han empleado técnicas de inferencia estadística.
El antecedente médico más frecuente fueron la enfermedad neurológica y la HTA, seguida de las enfermedades reumatológicas. Los motivos de consulta principales fueron el deterioro del estado general, la disnea, la disminución del nivel de consciencia y la fiebre. Se debe destacar la incidencia de la polifarmacia, especialmente de fármacos como los diuréticos, benzodiacepinas o hipnóticos. En relación con la etiología principal, destaca el papel de las infecciones de tipo urinario y respiratorio.
Se destaca el papel fundamental de las enfermedades neurológicas (especialmente la demencia), la HTA, la polifarmacia (uso inadecuado de benzodiacepinas e hipnóticos) y las infecciones urinarias y respiratorias como factores tratables o prevenibles del delirium en el paciente de Atención Primaria en nuestro medio.
To better understand the clinical, functional and analytical variables associated with delirium in emergencies and their evolution in order to obtain an improvement in the therapeutic approach of the elderly patient, thus preventing morbidity and mortality in this type of patient.
This is a prospective descriptive study of acute confusional syndrome in the emergency department.
General University Hospital of Ciudad Real.
All patients from the emergency department with a diagnosis of delirium were included in the 24-h interval following admission to the geriatric service.
An analysis of the variables of the data set (sociodemographic and clinical variables) was performed, calculating frequency tables for qualitative variables and descriptive statistics for quantitative variables. Subsequently, statistical inference techniques have been used.
The most frequent medical antecedent were neurological pathology and hypertension, followed by rheumatologic diseases. The main reasons for consultation were deterioration in general condition, dyspnea, decreased level of consciousness, and fever. Highlight the incidence of polypharmacy, especially drugs such as diuretics, benzodiazepines or hypnotics. In relation to the main etiology, the role of urinary and respiratory infections is noteworthy.
Highlight the fundamental role of neurological diseases (especially dementia), hypertension, polypharmacy (inappropriate use of benzodiazepines and hypnotics) and urinary and respiratory infections as treatable and/or preventable factors of delirium in Primary Care patients in our setting.
Introducción: La obesidad es una enfermedad que se ha convertido en una preocupación importante de salud pública. El objetivo de esta investigación, fue analizar los cambios en la calidad de vida y ...en parámetros clínicos, fisiológicos y antropométricos en pacientes con obesidad, pertenecientes a un programa multidisciplinario para pérdida de peso.
Materiales y métodos: Estudio observacional de cohorte retrospectivo que incluyó pacientes con obesidad en un programa multidisciplinario. La comparación de variables cuantitativas al ingreso y egreso del programa se realizó con la prueba de rangos con signo de Wilcoxon, mientras que las variables cualitativas fueron comparadas con la prueba de McNemar. El análisis estadístico fue realizado en el programa STATA V.15.
Resultados: Se analizaron 323 pacientes, se observó que la mediana del peso disminuyo 4.4 kg (p<0.001). La adherencia a la actividad física aumentó de 30% (n=97) a 90% (n=289) (p<0.001). De igual modo, la mediana del VO2 max aumentó de 23.6 (RIC 19.7-30.4) al ingreso a 32.9 (RIC 27.8-38) al egreso. En cuanto a calidad de vida, el autocuidado fue una de las dimensiones con mayor impacto durante el programa, con una disminución en el reporte de dificultades extremas de 17.7% a 0.3%. Asimismo, la escala visual análoga (EVA) aumento la mediana de 50 (RIC 50-70) a 80 (RIC 70-90) (p<0.001).
Conclusión: El abordaje multidisciplinario de la obesidad ofrece un enfoque integral al paciente, impactando no solo aspectos físicos, sino psicológicos y emocionales del problema mejorando su calidad de vida.
Introduction: Obesity is a disease that has become a major public health concern. The objective of this research was to analyze the changes in the quality of life and in clinical, physiological, and anthropometric parameters in patients with obesity, belonging to a multidisciplinary program for weight loss.
Materials and methods: Observational retrospective cohort study that included obese patients in a multidisciplinary program. The comparison of quantitative variables at admission and discharge from the program was performed with the Wilcoxon signed rank test, while the qualitative variables were compared with the McNemar test. Statistical analysis was performed in the STATA V.15 program.
Results: 323 patients were analyzed; it was shown that the median weight decreased 4.4 kg (p<0.001). Adherence to physical activity increased from 30% (n=97) to 90% (n=289) (p<0.001). Similarly, the median VO2 max increased from 23.6 (IQR 19.7-30.4) on admission to 32.9 (IQR 27.8-38) on discharge. Regarding quality of life, self-care was one of the dimensions with the greatest impact during the program, with a decrease in the report of extreme difficulties from 17.7% to 0.3%. Likewise, the visual analogue scale (VAS) increased the median from 50 (RIC 50-70) to 80 (RIC 70-90) (p<0.001).
Conclusion: The multidisciplinary approach to obesity offers a comprehensive approach to the patient, impacting not only physical, but also psychological and emotional aspects of the problem, improving her quality of life.
PDF
