Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.

Her2-Positive and Microsatellite Instability Status in Gastric Cancer-Clinicopathological Implications.

Gastric cancer (GC) is one of the leading causes of cancer-related death. The combination of new molecular classifications with clinicopathological data could contribute to the individualization of patients and to the development of new therapeutic strategies. We examined the various associations in two molecular types of GC: HER2-positive (human epidermal growth factor receptor 2) and microsatellite instability (MSI), assessing their influence on treatment and prognosis. A retrospective study of 142 GC patients was performed with molecular characterization through HER2 overexpression and DNA repair protein expression for MSI. The percentage of HER2-positive tumors was 13.4%, predominantly in men. Correlations were found with intestinal type, metastases, advanced stages and chemotherapy. Almost 75% of HER2-positive patients died. MSI occurred in 16.2%, associated with advanced age, female sex, distal location and intestinal type. These patients had few metastases and low stages. The percentage of deaths was higher among MSI patients who received perioperative chemotherapy. The determination of HER2 and MSI status in GC is important for their association with specific clinicopathological features and for their prognostic and predictive value.

Quality of life in school-age children with shunt implantation due to neonatal posthemorrhagic hydrocephalus.

PURPOSE: To assess the functional outcome in school-age children shunted in the neonatal period due to post-hemorrhagic hydrocephalus (PHH), using the HOQ-Spanish version (HOQ-sv), and to analyze predictors of quality of life in this group. METHODS: A cross-sectional study was performed between 2015 and 2018. Parents of pediatric patients with PHH attending our neurosurgery outpatient clinic were invited to complete the HOQ-sv and to enroll in the study. Clinical variables regarding the patients' neonatal course and surgical outcome were recorded. A descriptive analysis was done, and independent variables related to the HOQ scores were studied in univariate and multivariate analyses with regression trees. RESULTS: The study comprised a total of 52 patients. The mean overall HOQ score was 0.67 (on a scale from 0 [worse] to 1 [best]). The quality of life for the PHH children at school age was related to perinatal factors (gestational age at birth, time until shunt surgery, length of hospitalization at the time of shunt implantation, and comorbidity), shunt complications (symptomatic overdrainage, number of shunt revisions, and shunt revisions related to infection during the first year after treatment), and clinical background (seizures, spasticity, Gross Motor Function Classification System level or visual impairment). CONCLUSION: HOQ dimension scores in school-age children shunted due to PHH in our center were similar to those of referral centers for other etiologies of pediatric hydrocephalus. Future goals should be the prevention of complications related to worse outcomes at the time of diagnosis and to try to improve shunt performance later.

Functional outcome in pediatric hydrocephalus: results of applying the Spanish version of the Hydrocephalus Outcome Questionnaire.

OBJECTIVE The aims of the study were to assess whether the Spanish version of the Hydrocephalus Outcome Questionnaire (HOQ) could be useful for the evaluation and comparison of outcomes in the patients in the authors' region with those in patients in other institutions and to analyze predictors of functional outcome in patients with a shunt. METHODS The authors performed this cross-sectional study between March 2015 and April 2016. All the parents of a pediatric patient with hydrocephalus who attended the Hospital Regional Universitario de Málaga neurosurgery outpatient clinic were invited to enroll in the study and complete the HOQ-Spanish version. Age at diagnosis and at the time of the study, clinical data, shunt complications, and socioeconomic factors were also recorded. A descriptive analysis was performed, and independent variables related to the HOQ scores were studied. RESULTS A total of 132 patients participated in the study (100% participation rate). The mean ages were 16.74 months (range 0-142 months) at diagnosis and 10.45 years (range 5-16 years) at the time of the study. The mean overall HOQ score was 0.68 (on a scale from 0 [worse] to 1.0 [best]). Factors related to a worse quality of life were seizures, motor or visual impairment, shunt infection, need for shunt revision, need for more than 2 shunt revisions (range 0-8 revisions), symptomatic overdrainage, and older age at the time of the study. CONCLUSIONS The HOQ-Spanish version is useful in the authors' region; the dimension scores found in this study were comparable to those previously reported by referral centers. Future goals should be to prevent shunt complications, routinely get children to reach functional status, and refer patients for adjuvant therapy promptly.

Factors related to shunt survival in paediatric hydrocephalus. Could failure be avoided?

BACKGROUND: Improved shunt survival and a better understanding of factors related to failure in paediatric hydrocephalus still pose a challenge for neurosurgeons, in order to avoid morbidity and mortality, as well as the economic impact of repeated revision surgeries. For these reasons, an analysis is performed on the factors related to the first shunt failure in the long-term follow-up of a series in a single centre. METHODS: A retrospective review was conducted on 166 hydrocephalic paediatric patients shunted for the first time between 2000 and 2014. An analysis was made of the statistical relationships between first shunt failure and the demographic, aetiological, surgical and clinical variables. RESULTS: Of the 166 shunts implanted in our centre during the study period, 111 required revision over a mean follow-up period of 93 months. Factors significantly related to failure were post-haemorrhagic and post-infectious hydrocephalus, meningitis episode, posterior burr hole, differential pressure valve, standard catheter in first surgery, and symptomatic over-drainage. Multivariable analysis showed that previous meningitis and symptomatic over-drainage were risk factors for shunt failure, whereas frontal burr hole location and antibiotic-impregnated catheters were protective factors. Cox regression determined that independent factors significantly related to a worse shunt survival, were shunt infection and symptomatic over-drainage. CONCLUSIONS: Meningitis, symptomatic over-drainage, frontal burr hole, and antibiotic impregnated catheters are significant prognostic factors for shunt survival. Shunt infection and symptomatic over-drainage are independent factors significantly related to a shorter shunt survival. Prospective, randomised, controlled trials are required to validate these results.

Surgical outcome of the shunt: 15-year experience in a single institution.

PURPOSE: Surgical outcome after shunt insertion in pediatric hydrocephalus can vary greatly. Although first shunt survival rates and complications have been studied by several teams, much less is known about survival and complications of subsequent systems. The goals of this study were to evaluate the surgical outcome in a series of pediatric patients followed for a long time and establish the differences between first and subsequent extracranial shunt survival and complications. METHODS: We undertook a retrospective study in pediatric patients treated with ventriculoperitoneal shunts between 2000 and 2015 at our institution. Surgical outcome was assessed, and different shunt survival curves were studied with Kaplan-Meier. Complications related to each shunt failure were examined and compared. RESULTS: A total of 166 patients underwent 425 procedures, with a mean follow-up period of 93 months. The median number of shunt revision surgeries was 2. Shunt survival rates were better with the first shunt compared to those with the subsequent shunts. The main complication necessitating system revision surgery was overdrainage, the frequency of proximal and distal dysfunctions was similar in all the shunt failures, and isolated ventricle and infection were more frequent in younger patients. Shunt-related infections accounted for 7 % of the procedures, and the shunt independence rate was 10 %. CONCLUSIONS: The frequency of complications related to shunt failure in pediatric patients changes during follow-up. A strict protocol of overdrainage detection and active treatment could explain the need for repeat surgeries and the progressively shorter shunt survival time in our series.

Endoscopic Third Ventriculostomy Success Score (ETVSS) predicting success in a series of 50 pediatric patients. Are the outcomes of our patients predictable?

PURPOSE: In our series of endoscopic third ventriculostomy (ETV), we sought to establish the relationship between the preoperative prediction using the Endoscopic Third Ventriculostomy Success Score (ETVSS) and the postsurgical success rate. MATERIALS AND METHODS: This descriptive analytical study comprised 50 pediatric patients who underwent 58 ETV procedures between 2003 and 2011. Data regarding clinical, surgical, and radiological findings were obtained from a continuously updated database. For each patient, we calculated the ETVSS, based on the patient's age, hydrocephalus etiology, and presence of a previous shunt. We considered success to be an established or improved clinical state and at least one of the following radiological criteria: (a) reduction in ventricular size or stable ventricles with disappearance of periventricular edema and increased subarachnoid space over cerebral convexities, (b) flow artifact in sagittal T2FSE MR, or (c) bidirectional flow signal in 2D-CPC MR. Statistical significance was set at p < 0.05. Six months was the minimum postoperative follow-up required. RESULTS: The ETV was successful in 29 patients (58 %). Patients aged over 1 year achieved the best results (p < 0.019). For those who underwent successful ETV, the mean ETVSS was 71.03 (95 % CI, 66.23-75.84). In those for whom the ETV was not successful, the mean ETVSS was 60 (95 % CI, 53.09-66.90); (p < 0.007). CONCLUSIONS: The success of ETV in our series could have been predicted by ETVSS. Predictability could help establish stricter surgical selection criteria, thereby obtaining higher success rates, as well as preparing the patients and their families for expected outcomes.

Success criteria in pediatric neuroendoscopic procedures. Proposal for classification of results after 67 operations.

PURPOSE: Controversial issues exist concerning criteria for patient selection and long-term success in pediatric neuroendoscopic procedures. We designed a classification of success grades applicable to high-pressure and chronic hydrocephalus and also to those cases in which different endoscopic maneuvers are performed during the same procedure. We then evaluated the success rate and complications in our series. METHODS: A total of 59 patients underwent 67 neuroendoscopic procedures between January 2003 and January 2011. A retrospective study was made of the preoperative history, operative reports, and postoperative imaging findings and medical records. A 5-grade scale was developed to assess the type of success depending on clinical and radiological data. Complications related to the surgical procedure were also recorded. RESULTS: Two patients were excluded from the success analysis due to insufficient follow-up time. The final results for the first procedures in 57 patients were complete and permanent success (grade I) in 49.1%, complete but transitory success (grade II) in 10.5%, partial success (grade III) in 12.3%, doubtful success (grade IV) in 5.3%, and failure (grade V) in 22.8%. In eight cases a second procedure followed the failure of the first: grade I success was achieved in seven cases (87.5%) and grade V in one case (12.5%). The highest success rates were achieved in cases of hydrocephalus caused by tumors or arachnoid cysts and the lowest in slit ventricle syndrome. CONCLUSIONS: A common classification of degrees of success, such as that proposed here, would aid the development of comparative and cooperative studies.

[Mutations in precore/basal core promoter regions and viral polymerase in patients with chronic hepatitis B]. / Mutaciones de la región precore, promotor basal del core y polimerasa viral en pacientes con hepatitis B crónica.

BACKGROUND: Variations of C gene give rise to precore and basal core mutations, which influence HBeAg expression The antiviral treatment failure is due to the presence of variations in the gene P, which cause mutations in the viral polymerase. METHODS: We performed genotyping of HBV P gene by sequencing, and gene C in patients with chronic hepatitis B over a period of five years. RESULTS: A total of 75% of the patients had some mutation in precore or in basal core promoter regions, and 37% demonstrated resistance mutations to antiviral treatment. The most frequent genotypes were A and D. CONCLUSIONS: The presence of mutations in core/precore regions in patients with chronic hepatitis has led to tighter control of these patients. Detecting for resistance should be done as quickly as possible before there is an increase in viral load.

Confocal backscattering spectroscopy for leukemic and normal blood cell discrimination.

Leukemia is the most common pediatric cancer and leading cause of cancer related deaths in children. Improvements in the assessment of leukemic cells have the potential to influence not only the diagnosis of leukemia, but also the risk assessment of patients during the course of the treatment, both of which are important for improving the cure rate for this disease. In this study, we report on the design and performance of a confocal laser based system built to collect backscattered light over a range of 26° at 405, 488, and 633 nm to discriminate leukemic cells from normal red blood cells (RBC) and white blood cells (WBC). The design of the system is based on the spectral differences observed from spectroscopy measurements with a similar system designed with a white light source. Significant differences are observed in the intensity and wavelength dependence of leukemic cells from normal RBC and WBC. Specifically, the distinct light scattering of RBC is due to hemoglobin absorption, allowing for its discrimination from leukemic cells, mononuclear, and polymorphonuclear WBC particularly at certain wavelengths. Meanwhile, the high scattering intensities of polymorphonuclear WBC reflect the intracellular complexity of these cells in comparison to the leukemic or normal lymphocytes. Additionally, the detected light scattering spectra for leukemic cells are consistently steeper in comparison to normal WBC, which we attributed to differences in the fractal organization of intracellular scatterers. Based on our findings, the system has potential applications in the detection and quantification of leukemic cells in blood either in vivo or in vitro, using microfluidic-based systems, for disease monitoring.

Confocal backscattering-based detection of leukemic cells in flowing blood samples.

The prognostic value of assessing minimal residual disease (MRD) in leukemia has been established with advancements in flow cytometry and PCR. Nonetheless, these techniques are limited by high equipment costs, complex, and costly cell processing and the need for highly trained personnel. Here, we demonstrate the potential of exploiting differences in the relative intensities of backscattered light at three wavelengths to detect the presence of leukemic cells in samples containing varying mixtures of white blood cells (WBCs) and leukemic cells flowing through microfluidic channels. Using 405, 488, and 633 nm illumination, we identify distinct light scattering intensity distributions for Nalm-6 leukemic cells, normal mononuclear (PBMC) and polymorphonuclear (PMN) white blood cells and red blood cells. We exploit these differences to develop cell classification algorithms, whose performance is evaluated based on simultaneous acquisition of light scattering and fluorescence flow cytometry data. When this algorithm is used prospectively for the analysis of samples consisting of mixtures of PBMCs and leukemic cells, we achieve an average specificity and sensitivity of leukemic cell detection of 99.6 and 45.2%, respectively. When we consider samples that include leukemic cells along with PMNs and PBMCs, which can be acquired using a simple red blood cell lysis step following venipuncture, the specificity and sensitivity of the approach decreases to 91.6 and 39.5%, respectively. On the basis of the performance of these algorithms, we estimate that 42 or 71 µL of blood would be adequate to confirm the presence of leukemia at an 80% power level in samples containing 0.01% leukemia to either PBMCs or PBMCs and PMNs, respectively. Therefore, light scattering-based flow cytometry in a microfluidic platform could provide a low cost, highly portable, minimally invasive approach for detection and monitoring of leukemic patients. This could offer significant improvements especially for pediatric patients and for patients in developing countries.

Effects of skin temperature on lesion size in fractional photothermolysis.

BACKGROUND AND OBJECTIVES: Fractional photothermolysis is a new concept in cutaneous re-modeling whereby laser-induced microscopic zones of thermal injury (MTZ-Microscopic Treatment Zones) are surrounded by normal, viable tissue. This unique thermal damage pattern allows re-epithelialization in less than 24 hours. To increase patient comfort level during the procedure of fractional photothermolysis, simultaneous skin cooling has been proposed and is now extensively used. The purpose of this in vitro study was to examine the influence of skin temperature on the diameter of the epidermal microthermal zone and the extent of thermal injury per unit area. The determination of the changes in these parameters that are due to skin temperature will allow the better control and understanding of fractional photothermolysis at different skin temperatures. MATERIALS AND METHODS: Fractional photothermolysis was performed with a 1,550 nm fiber laser (Fraxel SR Laser) with 10 mJ per pulse on full-thickness cadaver skin. The skin samples were brought prior to exposure to temperatures that ranged from 0 to 45 degrees C. The epidermis of the skin samples was separated by dispase treatment, stained for thermal damage by NBTC stain, and lesion diameter was assessed by a blinded investigator. RESULTS: The average MTZ diameter exhibits a positive, linear relationship with skin temperature (R(2) = 0.904, P < 0.0001). As the skin temperature increases from 0 to 45 degrees C. The MTZ diameter increases from 93 to 147 microm (58%), and the MTZ area from 6,870 to 17,050 microm(2) (148%). CONCLUSION: The skin temperature affects the size of epidermal MTZs during fractional photothermolysis and is an important variable factor. The use of simultaneous skin cooling increases patient comfort; however, as it also decreases MTZ size, it may interfere with treatment efficacy. The control of skin temperature is necessary to provide a consistent outcome and to be able to compare treatments.

Impact of postoperative unwashed shed blood retrieved after total knee arthroplasty on endotoxin-stimulated tumor necrosis factor alpha release in vitro.

BACKGROUND: : Allogeneic or autologous blood seems to have an immunosuppressive effect that is largely attributable to storage-dependent factors. However, transfusion of postoperative unwashed shed blood (USB) after elective total knee replacement does not undergo storage. Therefore, the authors explored the effects of USB on the mitogen-driven cytokine synthesis by the patient's peripheral blood mononuclear cells. METHODS: : Perioperative blood samples were obtained from 12 total knee replacement patients with and 5 without reinfusion of leukoreduced USB, and from USB reinfusion line, before and after leukoreduction. Venous blood obtained at 4-6 postoperative hours was coincubated with USB. Endotoxin-stimulated release of tumor necrosis factor alpha and interleukin 10 was measured after 24 h of culture by solid-phase enzyme-labeled chemiluminescent immunometric assay. RESULTS: : Coincubation of postoperative venous blood with USB, USB cells, or USB plasma resulted in a significant depression of tumor necrosis factor-alpha synthesis, without significant effects on interleukin-10 synthesis. However, no differences were observed for endotoxin-stimulated cytokine release in perioperative blood samples from patients receiving or not receiving USB. CONCLUSION: : These data suggest that USB seemed to contain an antiinflammatory agent. However, at the actual retransfusion rate, USB does not seem to further enhance the immunosuppression that follows knee replacement surgery.

[Comparative study of the impact of diet versus pravastatin on color vision in Brodman area 19 detected by computerized chromatic analysis (CARDIOCOLOUR Study)]. / Estudio comparativo del impacto de la dieta frente a pravastatina en los centros de análisis cromático del área 19 de Brodman, mediante el análisis computarizado cromático (Estudio CARDIOCOLOUR).

INTRODUCTION AND OBJECTIVES: Hypercholesterolemia causes important neurodegenerative changes in the cerebral cortex, which are manifested by defects in the color perception by the neurons of Brodman area 19. Extensive interventional epidemiological data from both primary and secondary-prevention clinical trials indicate that cardiac ischemic events decrease when total cholesterol or LDL-C is reduced. Our goal was to elucidate the effects of diet compared with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin) on color perception using computerized chromatic analysis (CCA) and plasma cholesterol levels. PATIENTS AND METHODS: We studied 191 normotensive patients (133 men and 58 women) with pre-study plasma cholesterol levels in excess of 200 mg/dl. Seventy of these patients were treated with the American Heart Association Step II diet for six months. The remaining 121 were treated with pravastatin, 61 patients with 10 mg and 60 patients with 40 mg. They were examined by CCA after excluding any general or ophthalmological pathology. RESULTS: Chromatic vision recovered by 23% with diet, 38% with pravastatin 10 mg and 92% with pravastatin 40 mg. CONCLUSIONS: This study confirmed a strong association between therapeutic intervention with either diet or pravastatin and improved color vision.

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat.

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.