Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: a nationwide study in Spain.

OBJECTIVE: To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. SETTINGS: The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. PARTICIPANTS: This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. INTERVENTIONS: An exploratory factorial analysis was performed to select the most relevant variables of the sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. RESULTS: Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/105 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade ≥3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/105 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. CONCLUSIONS: Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/105 people/week) was a statistically independent predictor of mortality. TRIAL REGISTRATION NUMBER: CEIM 20/217.

Long term outcome and fusion rate of transdiscal fixation for L5-S1 high grade spondylolisthesis.

OBJECTIVE: High grade spondylolisthesis (HGS) is a quite rare entity and many techniques are available to address this condition. In 1994 Abdu et al. proposed a transdiscal fixation approach that achieved a good clinical outcome. We analyse outcome and fusion achieved in patients treated by transdiscal fixation after 1-year follow-up. METHODS: We reviewed patients operated through transdiscal fixation since 2014 with a follow-up of at least 1 year, and compared preoperative and postoperative clinical measures (ODI, VAS and EQ-5D) and postoperative complications. Also, we analyzed the degree of fusion on CT scan with Lenke and Birdwell criteria. RESULTS: Twelve patients were included in the study with a mean follow-up of 49.4 months (range 12.8-84.1 months). Three cases presented a Meyerding grade IV spondylolisthesis and 9 cases grade III. At 1-year follow-up mean postoperative ODI, VAS and EQ5D scores improved (ODI 13.2 (range 0-30) vs 49.83 (range 15-71.1); p = .005). Equally this improvement was seen in the last follow-up (ODI 9.28 (range 0-35) vs 49.83 (range 15-71.1); p = .005). CT scan showed fusion grade A in 5 patients (41.6%), another 5 as grade B (41.6%) in Lenke classification. According to the Birdwell criteria 4 patients were classified as grade I (33.3%), 7 patients grade II (58.3%). None showed complications postoperatively or radiolucency in follow-up. CONCLUSIONS: Transdiscal fixation shows a good clinical outcome that is maintained throughout a long time period and provides a reliable and suitable fusion.

Simulation with 3D Neuronavigation for Learning Cortical Bone Trajectory Screw Placement.

BACKGROUND AND OBJECTIVE: Learning a new technique in neurosurgery is a big challenge especially for trainees. In recent years, simulations and simulators got into the focus as a teaching tool. Our objective is to propose a simulator for placement of cortical bone trajectory (CBT) screws to improve results and reduce complications. METHODS: We have created a platform consisting of a sawbone navigated with a 3D fluoroscope to familiarize our trainees and consultants with CBT technique and later implement it in our department. Objective Structured Assessment of Technical Skills (OSATS) and Physician Performance Diagnostic Inventory Scale (PPDI) were obtained before and after the use of the simulator by the five participants in the study. Patients who were operated on after the implementation of the technique were retrospectively reviewed. RESULTS: During the simulation, there were 4 cases of pedicle breach out of 24 screws inserted (16.6%). After having completed simulation, participants demonstrated an improvement in OSATS and PPDI (p = 0.039 and 0.042, respectively). Analyzing the answers to the different items of the tests, participants mainly improved in the knowledge (p = 0.038), the performance (p = 0.041), and understanding of the procedure (p = 0.034). In our retrospective series, eight patients with L4-L5 instability were operated on using CBT, improving their Oswestry Disability Index (ODI) score (preoperative ODI 58.5 [SD 16.7] vs. postoperative ODI 31 [SD 13.4]; p = 0.028). One intraoperative complication due to a dural tear was observed. In the follow-up, we found a case of pseudoarthrosis and a facet joint violation, but no other complications related to misplacement, pedicle fracture, or hardware failure. CONCLUSION: The simulation we have created is useful for the implementation of CBT. In our study, consultants and trainees have valued very positively the learning obtained using the system. Moreover, simulation facilitated the learning of the technique and the understanding of surgical anatomy. We hope that simulation helps reducing complications in the future.

Language hemispheric dominance analyzed with magnetic resonance DTI: correlation with the Wada test.

OBJECTIVE: Language lateralization is a major concern in some patients with pharmacoresistant epilepsy who will face surgery; in these patients, hemispheric dominance testing is essential to avoid further complications. The Wada test is considered the gold standard examination for language localization, but is invasive and requires many human and material resources. Functional MRI and tractography with diffusion tensor imaging (DTI) have demonstrated that they could be useful for locating language in epilepsy surgery, but there is no evidence of the correlation between the Wada test and DTI MRI in language dominance. METHODS: The authors performed a retrospective review of patients who underwent a Wada test before epilepsy surgery at their institution from 2012 to 2017. The authors retrospectively analyzed fractional anisotropy (FA), number and length of fibers, and volume of the arcuate fasciculus and uncinate fasciculus, comparing dominant and nondominant hemispheres. RESULTS: Ten patients with temporal lobe epilepsy were reviewed. Statistical analysis showed that the mean FA of the arcuate fasciculus in the dominant hemisphere was higher than in the nondominant hemisphere (0.369 vs 0.329, p = 0.049). Also, the number of fibers in the arcuate fasciculus was greater in the dominant hemisphere (881.5 vs 305.4, p = 0.003). However, no differences were found in the FA of the uncinate fasciculus or number of fibers between hemispheres. The length of fibers of the uncinate fasciculus was longer in the dominant side (74.4 vs 50.1 mm, p = 0.05). Volume in both bundles was more prominent in the dominant hemisphere (12.12 vs 6.48 cm3, p = 0.004, in the arcuate fasciculus, and 8.41 vs 4.16 cm3, p = 0.018, in the uncinate fasciculus). Finally, these parameters were compared in patients in whom the seizure focus was situated in the dominant hemisphere: FA (0.37 vs 0.30, p = 0.05), number of fibers (114.4 vs 315.6, p = 0.014), and volume (12.58 vs 5.88 cm3, p = 0.035) in the arcuate fasciculus were found to be statistically significantly higher in the dominant hemispheres. Linear discriminant analysis of FA, number of fibers, and volume of the arcuate fasciculus showed a correct discrimination in 80% of patients (p = 0.024). CONCLUSIONS: The analysis of the arcuate fasciculus and other tract bundles by DTI could be a useful tool for language location testing in the preoperative study of patients with refractory epilepsy.

Does reintervention improve survival in recurrent glioblastoma? Facing a temporal bias in the literature.

BACKGROUND: Glioblastoma (GBM) is the most frequent intraaxial malignant brain tumour, in which recurrence management is a frequent and demanding issue. Recently, reintervention has emerged as a useful tool for treatment. However, some new evidence has shown that most of the articles published could have overestimated its effects. We aimed to analyse the effect on survival of reintervention considering it as a time-dependent variable and to compare it with classic statistical analysis. METHODS: We performed a retrospective study with GBM patients between 2007 and 2017. We compared the overall survival (OS) between reintervention and non-reintervention groups with time-dependent statistical methods (Simon-Makuch and landmarking methods and time-dependent multivariable Cox analysis) and compared them with those obtained with non-dependent time variable analysis. RESULTS: A total of 183 patients were included in the analysis and 44 of them were reoperated. The standard analysis with Kaplan-Meier and multivariable Cox regression of the cohort showed an OS of 22.2 months (95% CI 12.56-16.06) in the reintervention group and 11.8 months (95% CI 9.87-13.67) in the non-reintervention group (p < .001); and an HR 0.649 (95% CI 0.434-0.97 p = .035) for reintervention, demonstrating an increase in OS. However, time-dependent analysis with the Simon-Makuch test and the landmarking method showed that the relationship was not consistent, as this increase in OS was not significant. Moreover, time-dependent multivariable Cox analysis did not show that reintervention improved OS in our cohort (HR 0.997 95% CI 0.976-1.018 p = 0.75). CONCLUSIONS: There has been a temporal bias in the literature that has led to an overestimation of the positive effect of reintervention in recurrent GBM. However, reintervention could still be useful in some selected patients, who should be individualized according to prognostic factors related to the patient, biology of the tumour, and characteristics of surgical procedure.

Deep brain stimulation for aggressiveness: long-term follow-up and tractography study of the stimulated brain areas.

OBJECTIVE: Initial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors' objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders. METHODS: This was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation. RESULTS: The series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field. CONCLUSIONS: In this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.

Morphometrical evaluation of decompression obtained through corpectomy. Heading towards to posterior approaches. / Evolución morfométrica de descompresión obtenida tras corpectomía. Dirigiéndonos hacia abordajes posteriores.

INTRODUCTION: We analysed the decompression obtained by dorsal or dorsolumbar corpectomy measured by Cobb angle and the spinal area prior to and after surgery and compared the evolution of the technique over the last five years of the study. MATERIAL AND METHOD: A retrospective review of patients operated between 2005 and 2015 through anterior or posterior approaches was performed. RESULTS: 24 patients were studied and a significant improvement was observed between the preoperative and postoperative morphometrical measurement (4.18° correction of the kyphosis and an increase of 130.8mm2 in the spinal canal, p<.001 in both cases) and in clinical parameters (45.8% of patients improved in ASIA, and Karnofsky showed 13 points of improvement, p<.001 in both cases). However, there was no correlation between clinical and morphological parameters. We also observed that in the last five years of the study posterior approaches were more frequently used with good results. CONCLUSIONS: Dorsal corpectomy allows significant spinal decompression, with neurological improvement but this does not correlate with the measurement of decompression. Thanks to technical improvements, less invasive techniques (posterior approaches and MISS) allow good clinical results, which are similar to those obtained by anterior techniques.

Validation of Grading Scores and Outcome Prognostic Factors in Intracranial Meningiomas in Elderly Patients.

OBJECTIVE: Meningiomas are the most frequent benign intracranial tumors and they are becoming more frequent because of the aging population and advances in diagnostics and neurosurgical treatment. Therefore, there will be an increase of this disease in the coming years. METHODS: We performed a retrospective analysis of patients older than 70 years who underwent surgery for intracranial meningiomas, and we established risk factors related to outcome, morbidity, and mortality. We compared 3 previously described scores (Geriatric Scoring System [GSS], Clinico-Radiological Grading System [CRGS], and Sex, Karnofsky, ASA, Location and Edema [SKALE] score). RESULTS: We identified 110 patients older than 70 years. In the univariate analysis, postoperative Karnofsky Performance Status (KPS) was related to the presence of edema (P = 0.036), tumor size (P = 0.043), previous neurologic impairment (P = 0.012), and preoperative American Society of Anesthesiologists (ASA) physical status classification (P = 0.029). In the multivariable logistic regression model, ASA classification (odds ratio, 0.324; P = 0.04) and preoperative KPS (odds ratio, 1.042; P = 0.05) were also statistically significant. In all cases, better survival curves in the Kaplan-Meier survival test appear in patients with lower scores (CRGS, P = 0.015; GSS, P = 0.014; SKALE, P < 0.001). Also, morbidity measured as postoperative KPS correlated with these scores (CRGS, P < 0.001; SKALE, P < 0.001; GSS, P < 0.001). However, only SKALE correlated with perioperative morbidity, mortality, and 1-year mortality. CONCLUSIONS: Meningioma resection in patients older than 70 years is safe, with an acceptable rate of mortality and morbidity. Patients who should undergo surgery must be selected in relation to their comorbidities, such as ASA classification or preoperative KPS. However, SKALE could be a useful tool as an initial approach.

Image guidance in transdiscal fixation for high-grade spondylolisthesis in adults with correct spinal balance.

OBJECTIVE Spondylolisthesis is a prevalent spine disease that recent studies estimate could be detected in 9% of the population. High-grade spondylolisthesis (HGS), however, is much less frequent, which makes it difficult to develop a general recommendation for its treatment. Posterior transdiscal fixation was proposed in 1994 for HGS, and the use of spine navigation could make this technique more accessible and reduce the morbidity associated with the procedure. The purpose of this study was to present a case series involving adult patients with HGS and correct spinal alignment who were treated with transdiscal pedicle screw placement guided with neuronavigation and compare the results to those achieved previously without image guidance. METHODS The authors reviewed all cases in which adult patients with correct spinal alignment were treated for HGS with posterior transdiscal instrumentation placement guided with navigation between 2014 and 2016 at their institution. The authors compared preoperative and postoperative spinopelvic parameters on standing radiographs as well as Oswestry Disability Index (ODI) scores and visual analog scale (VAS) scores for low-back pain. Follow-up CT and MRI studies and postoperative radiographs were evaluated to identify any screw malplacement or instrumentation failure. Any other intraoperative or postoperative complications were also recorded. RESULTS Eight patients underwent posterior transdiscal navigated instrumentation placement during this period, with a mean duration of follow-up of 16 months (range 9-24 months). Six of the patients presented with Meyerding grade III spondylolisthesis and 2 with Meyerding grade IV. In 5 cases, L4-S1 instrumentation was placed, while in the other 3 cases, surgery consisted of transdiscal L5-S1 fixation. There was no significant difference between preoperative and postoperative spinopelvic parameters. However, there was a statistically significant improvement in the mean VAS score for low-back pain (6.5 ± 1.5 vs 4 ± 1.7) and the mean ODI score (49.2 ± 19.4 vs 37.7 ± 22) (p = 0.01 and p = 0.012, respectively). Six patients reduced their use of pain medication. There were no intraoperative or postoperative complications during the hospital stay, and as of the most recent follow-up, no complications related to pseudarthrosis or hardware failure had been observed. CONCLUSIONS Treatment with posterior transdiscal pedicle screws with in situ fusion achieved good clinical and radiological outcomes in patients with HGS and good sagittal spinal balance. The use of navigation and image guidance was associated with improved results in this technique, including a reduction in postoperative and intraoperative complications related to screw malplacement, pseudarthrosis, and instrumentation failure.

Review of Cortical Bone Trajectory: Evidence of a New Technique.

This article summarizes recent evidence on the cortical bone trajectory (CBT) obtained from published anatomical, biomechanical, and clinical studies. CBT was proposed by Santoni in 2009 as a new trajectory that can improve the fixation of pedicle screws in response to screw loosening in osteoporotic patients. Recently, research interest has been growing with increasing numbers of published series and frequent reports of new applications. We performed an online database search using the terms "cortical bone trajectory," "pedicle screw," "CBT spine," "CBT fixation," "MISS CBT," and "traditional trajectory." The search included the PubMed, Ovid MEDLINE, Cochrane, and Google Scholar databases, resulting in an analysis of 42 articles in total. These covered three aspects of CBT research: anatomical studies, biomechanical parameters, and clinical cases or series. Compared to the traditional trajectory, CBT improves pullout strength, provides greater stiffness in cephalocaudal and mediolateral loading, and shows superior resistance to flexion/extension; however, it is inferior in lateral bending and axial rotation. CBT seems to provide better immediate implant stability. In clinical studies, CBT has shown better perioperative results for blood loss, length of stay in hospital, and surgery time; similar or better clinical postoperative scores; and similar comorbidity, without any major fixation system complications due to instrumentation failure or screw misplacement. In addition, advantages such as less lateral exposure allow it to be used as a minimally invasive technique. However, most of the clinical studies were retrospective case series or case-control studies; prospective evidence on this technique is scarce, making a definitive comparison with the traditional trajectory difficult. Nevertheless, we can conclude that CBT is a safe technique that offers good clinical results with similar biomechanical and perioperative parameters to those of the traditional trajectory. In addition, new applications can improve its results and make it useful for additional pathologies.

Estudio coste-beneficio de la vacunación contra varicela en Aragón / A cost-benefit analysis of varicella vaccination in Aragón

Fundamento. La varicela, enfermedad infecto-contagiosa que afecta a la infancia de forma benigna, puede complicarse en adultos y niños vulnerables y ser mortal. Existen vacunas eficaces. Se estudiaron retrospectivamente los costes que supuso esta enfermedad en la población aragonesa en el período 2004-2014 y las hospitalizaciones generadas. Se compararon con los gastos que supondría haber vacunado a esas personas y también los gastos de vacunar a la población de 1 año de edad durante todo ese período. Mediante un análisis coste-beneficio, se evaluó el impacto económico de la vacunación. Método. Se utilizaron datos de la Autonomía de Aragón (España) de estos 11 años (incidencia anual de varicela, altas hospitalarias por este motivo, precio de la consulta de atención primaria y de hospitalización de cada año, así como el coste de días de trabajo según el salario mínimo anual y medicaciones utilizadas). Se calcularon los costes capitalizados, se compararon con los gastos capitalizados de vacunación y se realizó un análisis de sensibilidad. Resultados. Se obtuvo un índice beneficio-coste de 1,6 vacunando y revacunando a todos los niños que se enfermaron. Resultó un índice beneficio-coste de 1,24 al vacunar a toda la población de 12 meses con vacuna de 28,59€. En estos 11 años, el 53% de las hospitalizaciones fueron niños menores de 5 años. Conclusiones. Las campañas públicas de vacunación con 2 dosis a población menor de 4 años suponen ahorro y rentabilidad porque el precio de la vacuna permite un índice beneficio-coste superior a 1. Es esperable una gran disminución de hospitalizaciones en la población de 3-4 años.

Background. Varicella, a contagious and infectious disease that is usually benign in children, may become complicated among adults and vulnerable children and may even be life-threatening. There are effective vaccines. A retrospective study was conducted about costs and resulting hospitalizations related to this disease in the population of Aragón in the 2004-2014 period. Costs were compared to the expenses that would have been incurred if those people had received the vaccine and also to the expenses of vaccinating the 1-year-old population over the entire period. A cost-benefit analysis was done to assess the economic impact of varicella vaccination. Method. Data for the 11-year period were provided by the Autonomous Community of Aragón (Spain) and included annual varicella incidence, hospital discharges of varicella cases, costs of primary health care visits and hospitalizations for each year, costs of each workday as per the minimum annual salary and of drugs used). Capitalized costs were estimated and compared to capitalized expenses of vaccination, and a sensitivity analysis was performed. Results. A benefit-cost ratio of 1.6 was obtained considering that all children who had varicella had been vaccinated and had received a booster dose. A benefit-cost ratio of 1.24 was obtained considering that the vaccine had been administered to every 1-year-old individual at a price of EUR 28.59 per vaccine. Over the 11-year period, 53% of hospitalizations corresponded to children younger than 5 years old. Conclusions. Public campaigns for the immunization of children younger than 4 years old with 2 doses lead to cost savings and are cost-effective because the vaccine price results in a benefit-cost ratio greater than 1. A major reduction is expected in the number of hospitalizations among children aged 3-4 years.

A cost-benefit analysis of varicella vaccination in Aragón. / Estudio coste-beneficio de la vacunación contra varicela en Aragón.

BACKGROUND: Varicella, a contagious and infectious disease that is usually benign in children, may become complicated among adults and vulnerable children and may even be life-threatening. There are effective vaccines. A retrospective study was conducted about costs and resulting hospitalizations related to this disease in the population of Aragón in the 2004-2014 period. Costs were compared to the expenses that would have been incurred if those people had received the vaccine and also to the expenses of vaccinating the 1-year-old population over the entire period. A cost-benefit analysis was done to assess the economic impact of varicella vaccination. METHOD: Data for the 11-year period were provided by the Autonomous Community of Aragón (Spain) and included annual varicella incidence, hospital discharges of varicella cases, costs of primary health care visits and hospitalizations for each year, costs of each workday as per the minimum annual salary and of drugs used). Capitalized costs were estimated and compared to capitalized expenses of vaccination, and a sensitivity analysis was performed. RESULTS: A benefit-cost ratio of 1.6 was obtained considering that all children who had varicella had been vaccinated and had received a booster dose. A benefit-cost ratio of 1.24 was obtained considering that the vaccine had been administered to every 1-year-old individual at a price of EUR 28.59 per vaccine. Over the 11-year period, 53% of hospitalizations corresponded to children younger than 5 years old. CONCLUSIONS: Public campaigns for the immunization of children younger than 4 years old with 2 doses lead to cost savings and are cost-effective because the vaccine price results in a benefit-cost ratio greater than 1. A major reduction is expected in the number of hospitalizations among children aged 3-4 years.

FUNDAMENTOS: La varicela, enfermedad infecto-contagiosa que afecta a la infancia de forma benigna, puede complicarse en adultos y niños vulnerables y ser mortal. Existen vacunas eficaces. Se estudiaron retrospectivamente los costes que supuso esta enfermedad en la población aragonesa en el período 2004-2014 y las hospitalizaciones generadas. Se compararon con los gastos que supondría haber vacunado a esas personas y también los gastos de vacunar a la población de 1 año de edad durante todo ese período. Mediante un análisis coste-beneficio, se evaluó el impacto económico de la vacunación. MÉTODO: Se utilizaron datos de la Autonomía de Aragón (España) de estos 11 años (incidencia anual de varicela, altas hospitalarias por este motivo, precio de la consulta de atención primaria y de hospitalización de cada año, así como el coste de días de trabajo según el salario mínimo anual y medicaciones utilizadas). Se calcularon los costes capitalizados, se compararon con los gastos capitalizados de vacunación y se realizó un análisis de sensibilidad. RESULTADOS: Se obtuvo un índice beneficio-coste de 1,6 vacunando y revacunando a todos los niños que se enfermaron. Resultó un índice beneficio-coste de 1,24 al vacunar a toda la población de 12 meses con vacuna de 28,59€. En estos 11 años, el 53% de las hospitalizaciones fueron niños menores de 5 años. CONCLUSIONES: Las campañas públicas de vacunación con 2 dosis a población menor de 4 años suponen ahorro y rentabilidad porque el precio de la vacuna permite un índice beneficio-coste superior a 1. Es esperable una gran disminución de hospitalizaciones en la población de 3-4 años.

Usefulness of Reintervention in Recurrent Glioblastoma: An Indispensable Weapon for Increasing Survival.

BACKGROUND: Glioblastoma is the most frequent primary brain tumor and despite of complete treatment survival is still poor. The aim of this study is to define the utility of reoperation for improving survival in patients with recurrent glioblastoma, and determine other prognostic factors associated with longer survival. METHODS: We performed a retrospective analysis of those patients who underwent surgery and compared those who were operated two or more times and those who received surgery only once. We studied overall survival (OS), progression-free survival (PFS), and clinical variables that could be related with higher survival. RESULTS: A total of 121 patients were eligible for the study, of whom 31 (25%) underwent reoperation. The reoperation group had a mean and median increase survival of 10.5 and 16.4 months in OS and 3.5 and 2.7 months for PFS compared with the non-reoperation group (P < 0.001 and 0.01, respectively). Although complications were higher in patients that underwent reintervention (19.3%) there was no statistical difference with complication rate in first surgery (12.4%, χ2 = 1.86; P = 0.40). Cox multivariable analysis revealed that age (hazard ratio [HR] 1.03; 95% confidence interval [CI], 1.006-1.055; P = 0.013), reoperation (HR, 0.48; 95% CI, 0.285-0.810; P = 0.006), extent of resection >95% (HR, 0.547; 95% CI, 0.401-0.748; P < 0.001), and complete adjuvant therapy (HR, 0.389; 95% CI, 0.208-0.726; P = 0.003) were correlated with a higher OS. CONCLUSIONS: Reoperation and the extent of resection (EOR) are the only surgical variables that neurosurgeons can modify to improve survival in our patients. Higher EOR and reoperation rates in patients who can be candidates for second surgery, will increase OS and PFS.

[Vaccine cold chain interruption in a primary care center and economic evaluation]. / Interrupción de la cadena de frío vacunal en un centro de atención primaria y su valoración económica.

OBJECTIVES: Cold chain control is one of the most important facts to ensure the effectiveness of vaccines links, which requires specific material and human resources for management. The principal objective is to evaluate the interruptions in cold chain of the last 6 years and the possible cost savings that would result in further improvements. METHOD: A retrospective and descriptive study based on a review of all cold chain interruptions during the last 6 years, at Valdefierro Primary Health Center. RESULTS: We had 5 interruptions, the maximum temperature reached was 23.1±3.4°C and the longest interruption lasted 25.2±20.7hours. 1611 vaccines were affected and 165 discarded. Total economic loss was 2.098,10 € and 33.611,64 € were savings. The electrical failure was the disruption cause in 5 cases. CONCLUSIONS: Equipment and staff are essential. The center did some corrective actions, such as minimizing refrigerator time control, minimum stock control, considering population changes, and the center has requested a electrical supply system.