Instrumented lumbar fusion in patients over 75 years of age: is it worthwhile?-a comparative study of the improvement in quality of life between elderly and young patients.

Background: Surgical treatment of degenerative lumbar disease in the elderly is controversial. Elderly patients have an increased risk for medical and surgical complications commensurate with their comorbidities, and concerns over complications have led to frequent cases of insufficient decompression to avoid the need for instrumentation. The purpose of this study was to evaluate clinical outcome between older and younger patients undergoing lumbar instrumented arthrodesis. Methods: This is a retrospective, comparative study of prospectively collected outcomes. One hundred and fifty-four patients underwent 1- or 2-level posterolateral lumbar fusion. Patients were divided into two groups. Group 1: 87 patients ≤65 years of age who underwent decompression and posterolateral instrumented fusion; Group 2: 67 patients ≥75 years of age who underwent the same procedures with polymethylmethacrylate (PMMA) pedicle-screw augmentation. Mean follow-up 27.47 months (range, 76-24 months). Results: Mean age was 49.1 years old (range, 24-65) for the younger group and 77.8 (range, 75-86) in the elderly group. Patients ≥75 years of age showed higher preoperative comorbidity (American Society of Anesthesiology, ASA: 1.7 vs. 2.4), and ≥2 systemic diseases with greater frequency (12.5% vs. 44.7%). No significant differences were found between the two groups in terms of postoperative complications, fusion, or revision rate. During follow-up, adjacent disc disease and adjacent fracture occurred significantly more in Group 2 (P<0.05). At the end of follow-up, there were no significant differences between the two groups in any of the clinical and health-related quality of life scores or satisfaction with treatment received. Conclusions: Osteoporosis represents a major consideration before performing spine surgery. Despite an obvious increased risk of complications in elderly patients, PMMA-augmented fenestrated pedicle screw instrumentation in spine fusion represents a safe and effective surgical treatment option to elderly patients with poor bone quality. Age itself should not be considered a contraindication in otherwise appropriately selected patients.

A prognostic six-gene expression risk-score derived from proteomic profiling of the metastatic colorectal cancer secretome.

The necessity to accurately predict recurrence and clinical outcome in early stage colorectal cancer (CRC) is critical to identify those patients who may benefit from adjuvant chemotherapy. Here, we developed and validated a gene-based risk-score algorithm for patient stratification and personalised treatment in early stage disease based on alterations in the secretion of metastasis-related proteins. A quantitative label-free proteomic analysis of the secretome of highly and poorly metastatic CRC cell lines with different genetic backgrounds revealed 153 differentially secreted proteins (fold-change >5). These changes in the secretome were validated at the transcriptomic level. Starting from 119 up-regulated proteins, a six-gene/protein-based prognostic signature composed of IGFBP3, CD109, LTBP1, PSAP, BMP1, and NPC2 was identified after sequential discovery, training, and validation in four different cohorts. This signature was used to develop a risk-score algorithm, named SEC6, for patient stratification. SEC6 risk-score components showed higher expression in the poor prognosis CRC subtypes: consensus molecular subtype 4 (CMS4), CRIS-B, and stem-like. High expression of the signature was also associated with patients showing dMMR, CIMP+ status, and BRAF mutations. In addition, the SEC6 signature was associated with lower overall survival, progression-free interval, and disease-specific survival in stage II and III patients. SEC6-based risk stratification indicated that 5-FU treatment was beneficial for low-risk patients, whereas only aggressive treatments (FOLFOX and FOLFIRI) provided benefits to high-risk patients in stages II and III. In summary, this novel risk-score demonstrates the value of the secretome compartment as a reliable source for the retrieval of biomarkers with high prognostic and chemotherapy-predictive capacity, providing a potential new tool for tailoring decision-making in patient care.

[Use of mobile immunization teams to increase influenza vaccination coverage among heatlthcare workers. A community intervention trial]. / Uso de equipos móviles para aumentar la cobertura vacunal antigripal entre el personal sanitario. Ensayo comunitario de intervención.

OBJECTIVE: The use of mobile immunization teams has been proposed as a strategy to increase influenza vaccination (IV) coverage among healthcare workers (HCW), but has not been evaluated in Primary Healthcare (PHC). The objective of this work was to determine if the use of mobile immunization teams increases IV coverage among HCW of a basic health area in the Valencian Community. METHODS: Community intervention trial that included all HCWs from a basic health area in the Valencian Community. The assignment was by conglomerates in one stage, with the HCWs of a health center as an intervention group and that of the rest of the centers as a control group. The intervention group was visited by a team consisting of a doctor and a nurse who offered on-site IV, while the control group did not receive such a visit. The independent variable was the visit of the mobile immunization team and the dependent variable was IV in the study season (2015-2016). Data analysis was done both for the total IV coverage and separately for sex, age, professional category and history of IV in the previous seasons. A McNemar test was used to compare frequency distributions of paired data. RESULTS: The control group went from 14 (31.8%) vaccinated in the 2014-2015 season to 19 (45.2%) in the 2015-2016 season, while the intervention group went from 19 (30.6%) to 34 (54.8%). Among the total of the WHCs it went from 33 (31.3%) vaccinated to 53 (50.0%). This increase was significant. By groups, the increase was significant among those who received the visit of the mobile team (p = 0.0003), but not in the control group (p = 0.18). CONCLUSIONS: The visit of a mobile immunization team is a significant factor favorable to IV among HCW in our setting.

OBJETIVO: El uso de equipos móviles ha sido propuesto como estrategia para aumentar la cobertura de vacunación antigripal (VAG) entre el personal sanitario (PS), pero no ha sido evaluado en Atención Primaria (AP). El objetivo de este trabajo fue determinar si el uso de equipos móviles aumenta la cobertura de la VAG entre el PS de una zona básica de salud de AP de la Comunidad Valenciana. METODOS: Ensayo de intervención comunitaria que incluyó a todo el PS de AP de una zona básica de salud de la Comunidad Valenciana. La asignación fue por conglomerados en una etapa, con el PS de un centro de salud como grupo de intervención y el del resto de centros como grupo control. El PS del grupo de intervención recibió la visita de un equipo formado por un médico y un enfermero que ofreció in situ la vacunación antigripal, mientras que el grupo control no recibió tal visita. La variable independiente fue la visita del equipo móvil y la variable dependiente fue la VAG en la temporada de estudio (2015-2016). El análisis de los datos se realizó tanto para las coberturas de VAG totales como separadamente por sexo, edad, categoría profesional y antecedentes de VAG en las temporadas anteriores. Para comparar las distribuciones de frecuencia de datos apareados se usó la prueba de McNemar. RESULTADOS: El grupo control pasó de 14 (31,8%) vacunados en la temporada 2014-2015 a 19 (45.2%) en la 2015-2016, mientras que el grupo de intervención pasó de 19 (30,6%) a 34 (54,8%). Entre el total del PS se pasó de 33 (31,3%) vacunados a 53 (50,0%). Este aumento fue significativo. Por grupos, el aumento fue significativo entre los que recibieron la visita del equipo móvil (p=0,0003), pero no en el grupo de control (p=0,18). CONCLUSIONES: La visita de un equipo móvil es un factor significativo favorable a la VAG entre el PS de AP en nuestro medio.

Uso de equipos móviles para aumentar la cobertura vacunal antigripal entre el personal sanitario. Ensayo comunitario de intervención / Use of mobile immunization teams to increase influenza vaccination coverage among heatlthcare workers. A community intervention trial

OBJETIVO: El uso de equipos móviles ha sido propuesto como estrategia para aumentar la cobertura de vacunación antigripal (VAG) entre el personal sanitario (PS), pero no ha sido evaluado en Atención Primaria (AP). El objetivo de este trabajo fue determinar si el uso de equipos móviles aumenta la cobertura de la VAG entre el PS de una zona básica de salud de AP de la Comunidad Valenciana. MÉTODOS: Ensayo de intervención comunitaria que incluyó a todo el PS de AP de una zona básica de salud de la Comunidad Valenciana. La asignación fue por conglomerados en una etapa, con el PS de un centro de salud como grupo de intervención y el del resto de centros como grupo control. El PS del grupo de intervención recibió la visita de un equipo formado por un médico y un enfermero que ofreció in situ la vacunación antigripal, mientras que el grupo control no recibió tal visita. La variable independiente fue la visita del equipo móvil y la variable dependiente fue la VAG en la temporada de estudio (2015-2016). El análisis de los datos se realizó tanto para las coberturas de VAG totales como separadamente por sexo, edad, categoría profesional y antecedentes de VAG en las temporadas anteriores. Para comparar las distribuciones de frecuencia de datos apareados se usó la prueba de McNemar. RESULTADOS: El grupo control pasó de 14 (31,8%) vacunados en la temporada 2014-2015 a 19 (45.2%) en la 2015-2016, mientras que el grupo de intervención pasó de 19 (30,6%) a 34 (54,8%). Entre el total del PS se pasó de 33 (31,3%) vacunados a 53 (50,0%). Este aumento fue significativo. Por grupos, el aumento fue significativo entre los que recibieron la visita del equipo móvil (p=0,0003), pero no en el grupo de control (p=0,18). CONCLUSIONES: La visita de un equipo móvil es un factor significativo favorable a la VAG entre el PS de AP en nuestro medio

OBJECTIVE: The use of mobile immunization teams has been proposed as a strategy to increase influenza vaccination (IV) coverage among healthcare workers (HCW), but has not been evaluated in Primary Healthcare (PHC). The objective of this work was to determine if the use of mobile immunization teams increases IV coverage among HCW of a basic health area in the Valencian Community. METHODS: Community intervention trial that included all HCWs from a basic health area in the Valencian Community. The assignment was by conglomerates in one stage, with the HCWs of a health center as an intervention group and that of the rest of the centers as a control group. The intervention group was visited by a team consisting of a doctor and a nurse who offered on-site IV, while the control group did not receive such a visit. The independent variable was the visit of the mobile immunization team and the dependent variable was IV in the study season (2015-2016). Data analysis was done both for the total IV coverage and separately for sex, age, professional category and history of IV in the previous seasons. A McNemar test was used to compare frequency distributions of paired data. RESULTS: The control group went from 14 (31.8%) vaccinated in the 2014-2015 season to 19 (45.2%) in the 2015-2016 season, while the intervention group went from 19 (30.6%) to 34 (54.8%). Among the total of the WHCs it went from 33 (31.3%) vaccinated to 53 (50.0%). This increase was significant. By groups, the increase was significant among those who received the visit of the mobile team (p = 0.0003), but not in the control group (p = 0.18). CONCLUSIONS: The visit of a mobile immunization team is a significant factor favorable to IV among HCW in our setting

Polµ deficiency induces moderate shortening of P53-/- mouse lifespan and modifies tumor spectrum.

Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polµ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53-/- mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polµ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background. Array comparative genomic hybridization (aCGH) analyses showed DNA copy number alterations in both P53-/- and Polµ-/-P53-/- lymphomas. Our results also indicate that the increase in sarcoma incidence in Polµ-/-P53-/- mice could be associated with Cdk4 and Kub3 amplification and overexpression. These results identify a role for Polµ in the prevention of sarcomagenesis on a murine P53-deficient background, in contrast to most other NHEJ factors.

Polµ deficiency increases resistance to oxidative damage and delays liver aging.

Polµ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polµ (Polµ(-/-)) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polµ(-/-) mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polµ(-/-) deficiency on liver aging. We found that old Polµ(-/-) mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polµ(-/-) liver showed reduced genomic instability and increased apoptosis resistance. However, Polµ(-/-) mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polµ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.

Increased learning and brain long-term potentiation in aged mice lacking DNA polymerase µ.

A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.

[The Alliance for the Prevention of Colorectal Cancer in Spain. A civil commitment to society]. / Alianza para la Prevención del Cáncer de Colon en España: un compromiso cívico con la sociedad.

Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together.

Differential requirement for H2AX and 53BP1 in organismal development and genome maintenance in the absence of poly(ADP)ribosyl polymerase 1.

Combined deficiencies of poly(ADP)ribosyl polymerase 1 (PARP1) and ataxia telangiectasia mutated (ATM) result in synthetic lethality and, in the mouse, early embryonic death. Here, we investigated the genetic requirements for this lethality via analysis of mice deficient for PARP1 and either of two ATM-regulated DNA damage response (DDR) factors: histone H2AX and 53BP1. We found that, like ATM, H2AX is essential for viability in a PARP1-deficient background. In contrast, deficiency for 53BP1 modestly exacerbates phenotypes of growth retardation, genomic instability, and organismal radiosensitivity observed in PARP1-deficient mice. To gain mechanistic insights into these different phenotypes, we examined roles for 53BP1 in the repair of replication-associated double-strand breaks (DSBs) in several cellular contexts. We show that 53BP1 is required for DNA-PKcs-dependent repair of hydroxyurea (HU)-induced DSBs but dispensable for RPA/RAD51-dependent DSB repair in the same setting. Moreover, repair of mitomycin C (MMC)-induced DSBs and sister chromatid exchanges (SCEs), two RAD51-dependent processes, are 53BP1 independent. Overall, our findings define 53BP1 as a main facilitator of nonhomologous end joining (NHEJ) during the S phase of the cell cycle, beyond highly specialized lymphocyte rearrangements. These findings have important implications for our understanding of the mechanisms whereby ATM-regulated DDR prevents human aging and cancer.

Altered hematopoiesis in mice lacking DNA polymerase mu is due to inefficient double-strand break repair.

Polymerase micro (Polmicro) is an error-prone, DNA-directed DNA polymerase that participates in non-homologous end-joining (NHEJ) repair. In vivo, Polmicro deficiency results in impaired Vkappa-Jkappa recombination and altered somatic hypermutation and centroblast development. In Polmicro(-/-) mice, hematopoietic development was defective in several peripheral and bone marrow (BM) cell populations, with about a 40% decrease in BM cell number that affected several hematopoietic lineages. Hematopoietic progenitors were reduced both in number and in expansion potential. The observed phenotype correlates with a reduced efficiency in DNA double-strand break (DSB) repair in hematopoietic tissue. Whole-body gamma-irradiation revealed that Polmicro also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polmicro function is required for physiological hematopoietic development with an important role in maintaining early progenitor cell homeostasis and genetic stability in hematopoietic and non-hematopoietic tissues.

[Current status of the prognostic value of molecular markers in patients with colorectal cancer and the prediction of response to adjuvant therapy]. / Estado actual del valor pronóstico de los marcadores moleculares en pacientes con cáncer colorrectal y la predicción de respuesta al tratamiento adyuvante.

Colorectal cancer is one of the best studied of all malignant diseases in terms of genetics and/or molecular prognostic factors. These factors, and relationships with prognosis, may have important implications especially in the design of surgical and adjuvant chemo-radiotherapy options. However, the true prognostic significance of all known factors has yet to be realised. We have reviewed the literature with specific focus on the role of molecular markers involved in prognosis and the prediction of response to adjuvant treatment.

Estado actual del valor pronóstico de los marcadores moleculares en pacientes con cáncer colorrectal y la predicción de respuesta al tratamiento adyuvante / Current status of the prognostic value of molecular markers in patients with colorectal cancer and the prediction of response to adjuvant therapy

El cáncer colorrectal es uno de los tumores mejor conocidos de todas las enfermedades malignas en términos genéticos y/o moleculares. Su conocimiento y su relación con el pronóstico puede tener importantes implicaciones, fundamentalmente en el diseño de estrategias quirúrgicas y de quimiorradioterapia adyuvante. Sin embargo, aún desconocemos el verdadero significado pronóstico de todos los factores hasta ahora estudiados. En este trabajo hemos revisado la literatura acerca del papel específico de los marcadores moleculares en cáncer colorrectal y su probable respuesta al tratamiento

Colorectal cancer is one of the best studied of all malignant diseases in terms of genetics and/or molecular prognostic factors. These factors, and relationships with prognosis, may have important implications especially in the design of surgical and adjuvant chemo-radiotherapy options. However, the true prognostic significance of all known factors has yet to be realised. We have reviewed the literature with specific focus on the role of molecular markers involved in prognosis and the prediction of response to adjuvant treatment

Hemorroidectomía con bisturí armónico (Ultracision®) frente a electrocauterio: ¿disminuye el dolor postoperatorio? / Harmonic scalpel (Ultracision®) versus electrocautery hemorrhoidectomy: does it reduce postoperative pain?

Objetivo. Evaluar el efecto sobre el dolor postoperatorio, las complicaciones derivadas de su manejo y los efectos sobre la cicatrización de las heridas en hemorroidectomías con bisturí armónico en comparación con el electrocauterio. Diseño. Estudio prospectivo, aleatorizado. Pacientes y método. Se aleatorizó a 72 pacientes consecutivos con hemorroides de grado 3-4 sintomáticas en 2 grupos: grupo 1 (bisturí armónico) y grupo 2 (electrocauterio). Se evaluaron las diferencias en ambos grupos en cuanto al dolor postoperatorio, el tiempo de cicatrización de la herida y la incontinencia. Resultados. El dolor postoperatorio fue significativamente menor en el grupo 1 en los días 1, 2 y 30 y similar al grupo 2 en los días 7 y 15. El número de analgésicos requeridos en 24 h fue también menor en el grupo 1 en los días 1, 2 y 7 (p = 0,037; p = 0,042; p = 0,049). No hubo diferencias significativas entre ambos grupos en los días 15 y 30. Solamente 2 pacientes del grupo 1 necesitaron analgesia de rescate con petidina, frente a 8 pacientes del grupo 2. El tiempo de cicatrización de la herida fue menor en el grupo 1 (26,3 ñ 3,2 días) que en el grupo 2 (35,2 ñ 2,4 días) (p = 0,049). Las complicaciones postoperatorias fueron similares en ambos grupos. Cuatro pacientes del grupo 1 presentaron retención urinaria y 1, una fisura anal. En el grupo 2, 4 pacientes presentaron retención urinaria y 2, impactación fecal. El grado de incontinencia posquirúrgica medida a los 7 días fue similar en ambos grupos, un 15,23 por ciento de los pacientes del grupo 1 y un 17,26 por ciento del grupo 2, presentaron escape ocasional de gas o moco menos de una vez a la semana (grado A1 de Pescatori). A las 4 semanas poscirugía todos los pacientes de ambos grupos estaban continentes. Conclusión. El estudio muestra que la hemorroidectomía realizada con bisturí armónico produjo menos dolor postoperatorio que la realizada con electrocauterio, sobre todo durante las primeras 48 h postoperatorias, sin afección significativa de la continencia anal y una rápida cicatrización de las heridas (AU)