Surgical planning and finite element analysis for the neurocraneal protection in cranioplasty with PMMA: A case study.

New developments in terms of additive manufacturing, computational tools and mathematical simulation techniques have favored the development of successful methodologies for the restoration or restitution of bone structures in the human body. Likewise, achievements in Materials Science have allowed the development of biocompatible composites capable of achieving mechanical characteristics and biological similarities comparable to those of natural bone. Without considering the advantages and disadvantages of some biomaterials with respect to others, this research aims to evaluate the surgical planning, the design process, the impact resistance and the critical deflection of a customized cranial implant manufactured from polymethylmethacrylate (PMMA). With the support of finite element methods (FEM), the level of neurocranial protection offered by the implant is assessed.

Usefulness of red cell distribution width to predict mortality in patients undergoing endovascular repair of abdominal aortic aneurysms.

BACKGROUND: Red cell distribution width (RDW) reflecting impaired erythropoyesis, has been associated with poor prognosis and mortality in several conditions. The aim of this study was to determine the relationship between RDW and the 5-year survival after the endovascular repair of abdominal aortic aneurysms (EVAR) and its ability to improve the discriminative power of a survival predictive score. METHODS: Retrospective analysis of 284 patients undergoing EVAR at a single centre. The pattern of relationship between RDW and survival was assessed with penalized smoothing splines. Categorized RDW values were added to a predictive score based in standard preoperative variables, whose improvement in discriminative power was calculated on the basis of changes in the C-statistics and the continuous Net Reclassification Index (c-NRI). RESULTS: The survival rate at 5 years was 66.2% and was independently associated with hemoglobin (HR=0.85, P<0.004), statin intake (HR=0.54, P<0.004), heart failure (HR=2.53, P<0.018), atrial fibrillation (HR=2.53, P<0.000) and the non-revascularized coronary artery disease (HR=2.15, P<0.005). The relationship between RDW values and 5-year survival was linear. RDW-CV and RDW-SD were categorized to cut-off values of ≥15% (N.=83, 29.2%) and ≥50 fL (N.=82, 28.9%) that were independently associated with poorer 5-year survival rates (HR=2.03, CI 95%=1.29-3.19, P=0.002 and HR=1.89, CI 95%=1.21-2.95, P=0.005, respectively). The addition of the RDW CV or the RDW-SD to the baseline predictive score significantly improved the c-NRI (0.437, P<0.001 and 0.442, P<0.001, respectively). CONCLUSIONS: High preoperative RDW levels were linear and adversely related to 5-year survival after EVAR, improved the discriminative power of a predictive score based in standard preoperative variables and may help in decision-making at the time of surgical planning.

Influence of Operative Time in the Results of Infrainguinal Bypass for Chronic Limb Threatening Ischemia.

BACKGROUND: An increased operative time (OT) has been associated with a higher rate of adverse outcomes after several surgical procedures although scarce evidence exists for infrainguinal bypass surgery (IBS) and its impact beyond the postoperative period. The aim of this study was to define surgical characteristics related to a prolonged OT in IBS for chronic limb threatening ischemia and its influence on postoperative and 1-year outcomes. MATERIALS AND METHODS: Retrospective study of 249 consecutive patients (mean age 72.4 years, 73.1% male) undergoing IBS for CLI between 2008 and 2018. The characteristics related to the duration of surgery and its impact on outcome were assessed with a multiple linear regression and a multivariate logistic regression, respectively. RESULTS: Interventions associated with a prolonged OT included the bypass to a below-the-knee artery (additional 36 min, p = 0.002), the need for an alternative vein or a hybrid PTFE-vein graft (additional 37 min, p = 0.02) and inflow associated procedures (additional 47 min, p < 0.001). OT was associated with a higher rate of postoperative complications (OR for each additional 30 min 1.123, 95% CI 1.021-1.234) and need for a sociosanitary facility at discharge (OR 1.143, 95% CI 1.033-1.265). At 1-year of follow-up, OT was related to a higher major amputation rate (OR 1.201, 95% CI 1.036-1.393) and non-significantly to mortality (OR 1.125, 95% CI 0.999-1.268). CONCLUSIONS: A prolonged OT is a risk factor for adverse outcomes after IBS that extends beyond the immediate postoperative period. Further research is needed to evaluate how an expected high OT might influence decision-making.

Supervivencia de pacientes con diagnóstico de Cáncer de Cérvix, estadios clínicos IIB-IIIA-IIIB. SOLCA ­Cuenca. 2009 -2013 / Survival of patients diagnosed with Cervical Cancer, clinical stages IIB-IIIA-IIIB. SOLCA -Cuenca. 2009 -2013

Introducción: Lasupervivencia de pacientes con Cáncer de Cérvix se influencia por los estadíos clínicos de laenfermedad y por su histología. El objetivo de este estudio fue establecer la supervivencia en un grupo depacientes deun centro oncológico en Cuenca-Ecuador. Métodos:Es un estudio descriptivo, retrospectivo, analítico, en el cual se recopiló información de las historias clínicas y registros físicos del sistema médico de SOLCA ­Cuencapara establecer la Supervivencia durante el periodo 2009-2013.Se describen variables variables demográficas y clínicas (Tipode histología y estadío), Se compara la supervivencia entre laspacientes con estas variables. Resultados:Se incluyeron 150casos,edad media de 57.1 ±14.0años. El estado civil más prevalente fue el "casada"n=75/150 (50%), de procedencia Urbanan=83/150 (55.3%)de la provincia del Azuay (48.0%). El tipo histológico más prevalente fue el Cáncer epidermoide (92%), 60% en estadío clínico IIB. Mortalidad de 7casos. SupervivenciaGlobal (SG) 57.6 meses; con un EE de 0.88 y un IC 95% con rango de 55.9 a 59.4meses.SG en el estadio IIB fue de58.4 meses(EE: 0.91; IC 95%:56.63 ­60.20). En el estadio IIIB fue de 56.3 meses(EE: 1.85; IC 95%: 52.71 ­59.96), no se encontró diferencia estadística (P= 0.45). La SGfue mayor en el carcinoma epidermoide (Media: 58.2 meses; EE: 0.79, IC 95%: 57.70 a 59.81) en relación a la variante adenocarcinoma (Media: 50.08 meses; EE: 6.26; IC 95%: 37.81 a 62.36), con significancia estadística (P=0.045). Conclusión:La supervivencia global fue de 57.6 meses, con diferencia de supervivencia para el tipo histológico, siendo el mayor para carcinoma epidermoide 8 meses menos para el adenocarcinoma. No hubo diferencias entre la supervivencia entre estadíos clínicos IIB y IIIB

Introduction: The survival of patients with Cervical Cancer is influenced by the clinical stages of the disease and its histology. The objective of this study was to establish survival in a group of patients from an oncology center in Cuenca-Ecuador. Methods: It is a descriptive, retrospective, analytical study, in which information was collectedfrom the medical records and physical records of the SOLCA -Cuenca medical system to establish Survival during the period 2009-2013. Demographic and clinical variables are described ( Type of histology and stage), Survival is compared between patients with these variables. Results: 150 cases were included, mean age of 57.1 ± 14.0 years. The most prevalent marital status was "married" n = 75/150 (50%), of urban origin n = 83/150 (55.3%) from the province of Azuay (48.0%). The most prevalent histological type was epidermoid cancer (92%), 60% in clinical stage IIB. Mortality of 7 cases. Overall Survival (OS) 57.6 months; with a SE of 0.88 and a 95% CI with a range of 55.9 to 59.4 months. OS in stage IIB was 58.4 months (SE: 0.91; 95% CI: 56.63 -60.20). In stage IIIB it was 56.3 months (SE: 1.85; 95% CI: 52.71 -59.96), no statistical difference was found (P = 0.45). OS was higher in squamous cell carcinoma (Mean: 58.2 months; SE: 0.79, 95% CI: 57.70 to 59.81) in relation to the adenocarcinoma variant (Mean: 50.08 months; SE: 6.26; 95% CI: 37.81 to 62.36), with statistical significance (P= 0.045). Conclusion: Overall survival was 57.6 months, with a survival difference for histological type, the longest being for squamous cell carcinoma 8 months less for adenocarcinoma. There were no differences between survival between clinical stages IIB and IIIB

Endogenous plasma and salivary uracil to dihydrouracil ratios and DPYD genotyping as predictors of severe fluoropyrimidine toxicity in patients with gastrointestinal malignancies.

OBJECTIVE: The aim of this study was to evaluate the use of plasma and saliva uracil (U) to dihydrouracil (UH2) metabolic ratio and DPYD genotyping, as a means to identify patients with dihydropyrimidine dehydrogenase (DPD) deficiency and fluoropyrimidine toxicity. METHODS: Paired plasma and saliva samples were obtained from 60 patients with gastrointestinal cancer, before fluoropyrimidine treatment. U and UH2 concentrations were measured by LC-MS/MS. DPYD was genotyped for alleles *7, *2A, *13 and Y186C. Data on toxicity included grade 1 to 4 neutropenia, mucositis, diarrhea, nausea/vomiting and cutaneous rash. RESULTS: 35% of the patients had severe toxicity. There was no variant allele carrier for DPYD. The [UH2]/[U] metabolic ratios were 0.09-26.73 in plasma and 0.08-24.0 in saliva, with higher correlation with toxicity grade in saliva compared to plasma (rs=-0.515 vs rs=-0.282). Median metabolic ratios were lower in patients with severe toxicity as compared to those with absence of toxicity (0.59 vs 2.83 saliva; 1.62 vs 6.75 plasma, P<0.01). A cut-off of 1.16 for salivary ratio was set (AUC 0.842), with 86% sensitivity and 77% specificity for the identification of patients with severe toxicity. Similarly, a plasma cut-off of 4.0 (AUC 0.746), revealed a 71% sensitivity and 76% specificity. CONCLUSIONS: DPYD genotyping for alleles 7, *2A, *13 and Y186C was not helpful in the identification of patients with severe DPD deficiency in this series of patients. The [UH2]/[U] metabolic ratios, however, proved to be a promising functional test to identify the majority of cases of severe DPD activity, with saliva performing better than plasma.

Improved determination of uracil and dihydrouracil in plasma after a loading oral dose of uracil using high-performance liquid chromatography with photodiode array detection and porous graphitic carbon stationary phase.

OBJECTIVES: The aim of this study was to develop and validate a high-performance liquid chromatographic method for the measurement of plasma concentrations of uracil and dihydrouracil after administration of an oral loading dose of uracil in the context of evaluation of DPD enzyme activity. DESIGN AND METHODS: Analytes were extracted from 500µL plasma sampler with a mixture of ethyl acetate isopropanol (85:15, v/v) after protein precipitation with solid ammonium sulfate. The extract was inject in the porous graphitic carbon stationary phase, eluted with water and acetonitrile in gradient mode, allowing complete separation of uracil, dihydrouracil and the internal standard (5-fluorouracil). Chromatograms were monitored at 210 and 260nm. RESULTS: Total chromatographic run time, including reequilibration, was 30min. The assay was linear in the concentration range of 0.2 to 20µgmL(-1). Accuracy was 98.4-105.3%, intra-assay precision was 5.1-12.1% and between-assay precision was of 5.3-10.1%. Analytes were stable in plasma at room temperature up to 6h and for three freeze and thaw cycles. Processed samples are stable up to 12h. CONCLUSIONS: The developed method was fully validated and has significantly reduced running time when compared to previous assay using porous graphitic stationary phase, allowing complete resolution of uracil, dihydrouracil and internal standard. This assay might be suitable to investigate the eventual correlation between concentrations of uracil and dihydrouracil in plasma after an oral loading dose and DPD enzyme activity, with potential contribution to therapeutic drug monitoring.