Innovative pathological network-based multitarget approaches for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is a major health threat globally. Its prevalence is forecasted to exponentially increase during the next 30 years due to the global aging population. Currently, approved drugs are merely symptomatic, being ineffective in delaying or blocking the relentless disease advance. Intensive AD research describes this disease as a highly complex multifactorial disease. Disclosure of novel pathological pathways and their interconnections has had a major impact on medicinal chemistry drug development for AD over the last two decades. The complex network of pathological events involved in the onset of the disease has prompted the development of multitarget drugs. These chemical entities combine pharmacological activities toward two or more drug targets of interest. These multitarget-directed ligands are proposed to modify different nodes in the pathological network aiming to delay or even stop disease progression. Here, we review the multitarget drug development strategy for AD during the last decade.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Prehospital transfusion of allogeneic blood products.

PURPOSE OF REVIEW: The purpose of this article is to provide a structural and practical analysis of the currently available data concerning prehospital transfusion of allogeneic blood products in cases of trauma and severe bleeding. RECENT FINDINGS: Prehospital transfusion of allogeneic blood products is a very early intervention, which may offer the potential to improve outcome, but that also comes with challenges including resource allocation, blood product storage, logistics, patient selection, legal and ethical considerations, adverse effects, and costs. Potential benefits including improved stability and reduction in coagulopathy and blood loss have not yet been clearly demonstrated. SUMMARY: The questionable efficacy and challenges in clinical practice may outweigh the potential benefits of prehospital allogeneic transfusion.

The Spiritual Aspect of Pain: An Integrative Review.

Pain is an unpleasant sensory and emotional experience that affects individuals in various ways involving biological, psychological, social, and spiritual aspects. There is currently no comprehensive treatment that effectively addresses all aspects of pain. This integrative review aimed to analyze the spiritual aspect of pain relief. Following the specified methodological criteria, a total of 20 articles were selected. There evidenced a lack of spiritual care provided by healthcare professionals, even though its correlation with pain and its potential benefits have been widely demonstrated in the literature. Fortunately, some patients put into practice existential and religious tools to self-control and cope with their pain, although not always with a successful response.

tRNAstudio: facilitating the study of human mature tRNAs from deep sequencing datasets.

SUMMARY: High-throughput sequencing of transfer RNAs (tRNA-Seq) is a powerful approach to characterize the cellular tRNA pool. Currently, however, analyzing tRNA-Seq datasets requires strong bioinformatics and programming skills. tRNAstudio facilitates the analysis of tRNA-Seq datasets and extracts information on tRNA gene expression, post-transcriptional tRNA modification levels, and tRNA processing steps. Users need only running a few simple bash commands to activate a graphical user interface that allows the easy processing of tRNA-Seq datasets in local mode. Output files include extensive graphical representations and associated numerical tables, and an interactive html summary report to help interpret the data. We have validated tRNAstudio using datasets generated by different experimental methods and derived from human cell lines and tissues that present distinct patterns of tRNA expression, modification and processing. AVAILABILITY AND IMPLEMENTATION: Freely available at https://github.com/GeneTranslationLab-IRB/tRNAstudio under an open-source GNU GPL v3.0 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mutation update for the ACTN2 gene.

ACTN2 encodes alpha-actinin-2, a protein expressed in human cardiac and skeletal muscle. The protein, located in the sarcomere Z-disk, functions as a link between the anti-parallel actin filaments. This important structural protein also binds N-terminal titins, and thus contributes to sarcomere stability. Previously, ACTN2 mutations have been solely associated with cardiomyopathy, without skeletal muscle disease. Recently, however, ACTN2 mutations have been associated with novel congenital and distal myopathy. Previously reported variants are in varying locations across the gene, but the potential clustering effect of pathogenic locations is not clearly understood. Further, the genotype-phenotype correlations of these variants remain unclear. Here we review the previously reported ACTN2-related molecular and clinical findings and present an additional variant, c.1840-2A>T, that further expands the mutation and phenotypic spectrum. Our results show a growing body of clinical, genetic, and functional evidence, which underlines the central role of ACTN2 in the muscle tissue and myopathy. However, limited segregation and functional data are available to support the pathogenicity of most previously reported missense variants and clear-cut genotype-phenotype correlations are currently only demonstrated for some ACTN2-related myopathies.

Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Bombyx mori Fibers.

High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers.

Beta-amyloid peptides(1-42) and (1-40) in the cerebrospinal fluid during pregnancy: a prospective observational study.

To evaluate changes in concentrations of selected biomarkers, neurotrophic factors, and growth factors in the cerebrospinal fluid during pregnancy. A prospective observational study was conducted in 32 pregnant women undergoing gynecological and obstetrical surgery under spinal anesthesia in a university hospital. Beta-amyloid(1-42) and beta-amyloid(1-40) peptides, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and vascular endothelial growth factor were analyzed in cerebrospinal fluid using an enzyme-linked immunosorbent assay. Eight women in second trimester pregnancy who underwent spinal anesthesia for gynecological or obstetrical surgery were compared with 24 matched women in third trimester pregnancies. CSF concentrations of beta-amyloid(1-42) were significantly higher in third trimester pregnancies (p = 0.025). During third trimester, the beta-amyloid ratio correlated with the vascular endothelial growth factor (rs = 0.657; p = 0.008). Higher concentrations of beta-amyloid(1-42) in cerebrospinal fluid of third trimester pregnancies and correlations between the beta-amyloid ratio and the vascular endothelial growth factor support the hypothesis that beta-amyloid peptides are involved in complex adaptive brain alterations during pregnancy.

[Descriptive analysis of medication errors notified by Primary Health Care: Learning from errors]. / Análisis descriptivo de los errores de medicación notificados en atención primaria: aprendiendo de nuestros errores.

INTRODUCTION AND OBJECTIVES: Aim of this study is to determine the setting, causes, and the harm of medication errors (ME) which are notified by Primary Health Care. MATERIAL AND METHODS: Setting: Primary Care Regional Health Service of Madrid. 2016. DESIGN: Descriptive and cross-sectional study. PARTICIPANTS: All ME (1,839) which were notified by Primary Care Centres by notification system of safety incidents between January 1st 2016 and November 17th 2016. MAIN MEASUREMENTS: Setting, real harm, potential harm, and cause of error. These items were classified by one researcher. Concordance was checked with another researcher. RESULTS: Just under half (47%) (95% CI: 44.8%-49.3%) of ME occurred in Primary Care Centre, 26.5% (95% CI: 24.5%-28.6%) of ME were patient medication errors, and 27.5% (95% CI: 24.1%-30.8%) of ME were potential severe harm errors. Prescribing errors were the cause of most ME in Primary Care Centre [27.4% (95% CI: 24.4%-30.4%)]. Communication between patients and doctors were the cause of most patient medication errors [66% (95% CI: 61.8%-70.2%)]. Patient mistakes and forgetfulness were also causes of patient medication errors. CONCLUSIONS: Half of all mediation errors hppened at Primary Care Center while one quarter of them were patient medication errors. One quarter of all ME were potential severe harm errors. The main causes were prescribing errors, failure of communication between patients and doctors, and patient mistakes and forgetfulness. Prescribing aid systems, communication improvements and patients aids should be implemented.

A Pilot, Phase II, Randomized, Open-Label Clinical Trial Comparing the Neurotoxicity of Three Dose Regimens of Nab-Paclitaxel to That of Solvent-Based Paclitaxel as the First-Line Treatment for Patients with Human Epidermal Growth Factor Receptor Type 2-Negative Metastatic Breast Cancer.

BACKGROUND: This study aimed to characterize the neurotoxicity of three different regimens of nab-paclitaxel compared with a standard regimen of solvent-based (sb) paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer based on the Total Neurotoxicity Score (TNS), a tool specifically developed to assess chemotherapy-induced neurotoxicity. MATERIALS AND METHODS: This was a randomized, open-label study testing 4-week cycles of 80 mg/m2 sb-paclitaxel (PACL80/w) on days 1, 8, and 15; 100 mg/m2 nab-paclitaxel on days 1, 8, and 15 (NAB100/w); 150 mg/m2 nab-paclitaxel on days 1, 8, and 15 (NAB150/w); and 150 mg/m2 nab-paclitaxel on days 1 and 15 (NAB150/2w). In addition to the TNS, neuropathy was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Tumor response and quality of life were also evaluated. RESULTS: Neurotoxicity, as evaluated by the TNS, did not significantly differ between the sb-paclitaxel group and any of the nab-paclitaxel groups. The frequency of (any grade) polyneuropathy, as measured by the NCI-CTCAE, was lower in the PACL80/w (n = 7, 50%) and NAB150/2w (n = 10, 62.5%) groups than in the NAB100/w (n = 13, 81.3%) or NAB150/w (n = 11, 78.6%) group. Although the differences were not statistically significant, compared with the other groups, in the NAB150/w group, the time to occurrence of grade ≥2 polyneuropathy was shorter, and the median time to recovery from grade ≥2 polyneuropathy was longer. Dose delays and reductions due to neurotoxicity and impact of neurotoxicity on the patients' experience of symptoms and functional limitations was greater with NAB150/w. Among the seven polymorphisms selected for genotyping, the variant alleles of EPHA5-rs7349683, EPHA6-rs301927, and EPHA8-rs209709 were associated with an increased risk of paclitaxel-induced neuropathy. CONCLUSION: The results of this exploratory study showed that, regardless of the dose, nab-paclitaxel did not differ from sb-paclitaxel in terms of neurotoxicity as evaluated with the TNS. However, results from NCI-CTCAE, dose delays and reductions, and functional tools consistently indicate that NAB150/w regimen is associated with a greater risk of chemotherapy-induced neuropathy. Thus, our results question the superiority of the TNS over NCI-CTCAE for evaluating chemotherapy-induced neuropathy and guiding treatment decisions in this context. The selection of the nab-paclitaxel regimen should be individualized based on the clinical context and potentially supported by pharmacogenetic analysis. Registry: EudraCT, 2012-002361-36; NCT01763710 IMPLICATIONS FOR PRACTICE: The results of this study call into question the superiority of the Total Neurotoxicity Score over the National Cancer Institute Common Terminology Criteria for Adverse Events for evaluating chemotherapy-induced neuropathy and guiding treatment decisions in this context and suggest that a regimen of 150 mg/m2 nab-paclitaxel administered on days 1, 8, and 15 is associated with a greater risk of chemotherapy-induced neuropathy and hematological toxicity compared with other lower-dose nab-paclitaxel regimens or a standard regimen of solvent-based paclitaxel. The selection of the nab-paclitaxel regimen should be individualized based on the clinical context and could benefit from pharmacogenetics analysis.

Study of the effect of anti-rhGAA antibodies at low and intermediate titers in late onset Pompe patients treated with ERT.

Late onset Pompe disease (LOPD) is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzyme replacement therapy (ERT) with alglucosidase alpha (rhGAA). Although most of ERT treated patients develop antibodies against rhGAA, their influence on clinical progression is not completely known. We studied the impact of anti-rhGAA antibodies on clinical progression of 25 ERT treated patients. We evaluated patients at visit 0 and, after 1 year, at visit 1. We performed several muscle function tests, conventional spirometry and quantitative muscle MRI (qMRI) using 3-point Dixon analysis of thigh muscles at both visits. We also obtained serum samples at both visits and anti-rhGAA antibodies were quantified using ELISA. Antibody titers higher than 1:200 were identified in 18 patients (72%) of our cohort. Seven patients (28%) did not develop antibodies (0 to <1:200), 17 patients (68%) developed low to intermediate titers (1:200 to <1:31,200) and 1 patient (4%) developed high titers (>1:31,200). We analyzed the effect of low and intermediate antibody titers in clinical and radiological progression. There were no differences between the results of muscle function tests, spirometry or fat fraction analyzed using qMRI between patients with and without antibodies groups at baseline. Moreover, antibody titers did not influence muscle function test, spirometry results or qMRI results at year 1 visit. Most of the LOPD patients developed antibodies against ERT that persisted over time at low or intermediate levels. However, antibodies at these low and intermediate titers might not influence clinical response to the drug.

Photovaporization of the prostate with GreenLight™ laser 180 W XPS versus transurethral resection of the prostate with monopolar energy for the treatment of benign prostatic enlargement: a cost-utility analysis from a healthcare perspective.

PURPOSE: To assess the cost-utility of the photovaporization of the prostate (PVP) with GreenLight™ laser 180 W XPS compared to transurethral resection of the prostate with monopolar energy (M-TURP) for lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) from a healthcare perspective in Colombia. METHODS: We designed a Markov model to compare four health states following treatment with either PVP or M-TURP to estimate expected costs and outcomes. We used the results of the only randomized clinical trial published to date comparing PVP versus M-TURP to estimate surgical outcomes, complications, re-operation and re-intervention rates. Time horizon was defined at 2 years with four cycles of 6 months each. Resource-use estimation involved a random selection of clinical records from a local institution and cost list from public healthcare system. Costs were obtained in Colombian pesos and converted to US dollars. Threshold was defined at three-times the Colombian gross domestic product (GDP) per capita. Quality-adjusted-life-years (QALYs) were used based on the utilities of the available literature. Uncertainty was analyzed with deterministic and probabilistic models using a Monte Carlo simulation. RESULTS: Patients who underwent PVP gained 1.81 QALYs compared to 1.59 with M-TURP. Costs were US$6797.98 and US$7777.59 for M-TURP and PVP, respectively. Incremental cost-effectiveness ratio was US$4452.81 per QALY, favoring PVP as a cost-effective alternative in our context. CONCLUSIONS: In Colombia, with current prices, PVP is cost-effective when compared to M-TURP for LUTS due to BPE for a 2-year time horizon.

Diagnostic accuracy of multiparametric magnetic resonance imaging in detecting extracapsular extension in intermediate and high - risk prostate cancer.

OBJECTIVES: To evaluate the diagnostic performance of preoperative multiparametric magnetic resonance imaging (mp-MRI) as a predictor of extracapsular extension (ECE) and unfavorable Gleason score (GS) in patients with intermediate and high-risk prostate cancer (PCa). MATERIALS AND METHODS: Patients with clinically localized PCa who underwent radical prostatectomy (RP) and had preoperative mp-MRI between May-2011 and December-2013. Mp-MRI was evaluated according to the European Society of Urogenital Radiology MRI prostate guidelines by two different readers. Histopathological RP results were the standard reference. RESULTS: 79 patients were included; mean age was 61 and median preoperative prostate-specific antigen (PSA) 7.0. On MRI, 28% patients had ECE evidenced in the mp-MRI, 5% seminal vesicle invasion (SVI) and 4% lymph node involvement (LNI). At RP, 39.2% had ECE, 26.6% SVI and 12.8% LNI. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of mp-MRI for ECE were 54.9%, 90.9%, 76%, 81% and 74.1% respectively; for SVI values were 19.1%, 100%, 77.3%, 100% and 76.1% respectively and for LNI 20%, 98.4%, 86.7%, 66.7% and 88.7%. CONCLUSIONS: Major surgical decisions are made with digital rectal exam (DRE) and ultrasound studies before the use of Mp-MRI. This imaging study contributes to rule out gross extraprostatic extension (ECE, SVI, LNI) without competing with pathological studies. The specificity and NPV are reasonable to decide surgical approach. A highly experienced radiology team is needed to provide accurate estimations of tumor extension and aggressiveness.

Urological approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a clinical care center.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with significant manipulation of the urinary tract (UT). We aim to describe the urological events and their management in patients who underwent CRS-HIPEC. METHODS: Clinical records of patients who underwent treatment between 2007 and 2015 were reviewed. Urological events and their multidisciplinary management were analyzed. Descriptive statistics were calculated. RESULTS: A total of 103 patients were included. Mean age was 51 years (SD ± 11.8). Mean peritoneal cancer index (PCI) was 20.4 (SD ± 10.1). Primary tumors included appendicular (64%), gynecological (16%), colorectal (10%), and peritoneal mesotheliomas (9%). Ninety-three percent of patients had bilateral ureteral catheters inserted prior to surgery, without complications. Intraoperative UT injuries occurred in 7% of patients. In 5% of patients, tumor invasion of the bladder was evident at surgery and partial resection and primary repair of the bladder wall was performed. Urological complications included urinary tract infection (UTI) (21%) acute post-renal failure (4%), urinary fistulae (4%), and acute urinary retention (AUR) (1%). CONCLUSIONS: In our study, intraoperative UT events and postoperative complications, although not neglectable, were infrequent. Due to the high complexity of these cases, a multidisciplinary approach is mandatory. However, randomized clinical trials are necessary to clarify current data on the need and efficacy of prophylactic ureteral catheterization in patients undergoing CRS-HIPEC.

Decreased entropy modulation of EEG response to novelty and relevance in schizophrenia during a P300 task.

The analysis of the interaction between novelty and relevance may be of interest to test the aberrant salience hypothesis of schizophrenia (SCH). In comparison with other neuroimaging techniques, such as functional magnetic resonance imaging, electroencephalography (EEG) provides high temporal resolution. Therefore, EEG is useful to analyze transient dynamics in neural activity, even in the range of milliseconds. In this study, EEG activity from 31 patients with SCH and 38 controls was analyzed using Shannon spectral entropy (SE) and median frequency (MF). The aim of the study was to quantify differences between distractor (i.e., novelty) and target (i.e., novelty and relevance) tones in an auditory oddball paradigm. Healthy controls displayed a larger SE decrease in response to target stimulus than in response to distractor tones. SE decrease was accompanied by a significant and widespread reduction of MF (i.e., a significant slowing of EEG activity). In comparison with controls, patients showed a significant reduction of changes in SE in response to both target and distractor tones. These differences were also observed in patients that only received a minimal treatment prior to EEG recording. Furthermore, significant changes in SE were inversely correlated to positive and total symptoms severity for SCH patients. Our findings support the notion that SCH is associated with a reduced response to both novelty and relevance during an auditory P300 task.

Decreased spectral entropy modulation in patients with schizophrenia during a P300 task.

Spectral entropy (SE), also known as Shannon entropy, is a useful parameter for quantifying the global regularity of the electroencephalographic (EEG) signal. Hence, it is of interest in the assessment of the electrophysiological correlates of cognitive processing in schizophrenia. However, to date, SE has been barely used in studies comparing resting EEG recordings between patients and controls. In this work, we compared SE between resting baseline [-250 0] ms and active task [150 550] ms windows of a P300 task in 31 patients with schizophrenia and 38 controls. Moreover, we also calculated the median frequency (MF) and relative power in each frequency band for these windows to assess the correlates of the possible SE differences. Controls showed a significant (p < 0.0029) SE decrease (i.e., meaning higher signal regularity) from baseline to the active task window at parietal and central electrode sites. This SE decrease from baseline to active conditions was significantly lower in patients. In controls, this SE decrease was accompanied by a statistically significant decrease in MF (i.e., a significant slowing of the EEG activity), not observed in patients. In this latter group, the difference in SE between resting baseline and active task windows was inversely correlated to positive and total symptoms scores, as measured with the positive and negative symptoms scale. Our data support the relevance of SE in the study of cerebral processing in schizophrenia.

Room-temperature columnar mesophases in triazine-gold thiolate metal-organic supramolecular aggregates.

Supramolecular mono- and dinuclear liquid-crystalline gold(I) aggregates have been synthesized by means of hydrogen bond interactions of 2,4,6-triarylamino-1,3,5-triazine with thiolate moities of gold metalloacids [Au(PR3)(SC6H4COOH)] or [µ-(binap){Au(SC6H4COOH)}2], in 1:1 and 2:1 molar ratio, respectively. All of the supramolecular aggregates display a stable columnar hexagonal mesophase (Col(h)) at room-temperature. The supramolecular arrangement within the columns consists of the one-dimensional stacking of triazine units, with the core of the attached metallic thioacid fragments acting as the fourth branch. The phosphine-containing moieties of the metallic thioacid protrude out in the aliphatic continuum. These complexes do not show metallophilic interactions, but this strategy appears very promising for the future design of room-temperature LC mesophases containing interacting metallic fragments.

Physicochemical characterization of Acidiphilium sp. biofilms.

The biofilm formation of a strain of the extremophile bacterium Acidiphilium sp., capable of donating electrons directly to electrodes, was studied by different surface characterization techniques. We develop a method that allows the simultaneous study of bacterial biofilms by means of fluorescence microscopy and atomic force microscopy (AFM), in which transparent graphitic flakes deposited on a glass substrate are used as a support for the biofilm. The majority of the cells present on the surface were viable, and the growth of the biofilms over time showed a critical increase of the extracellular polymeric substances (EPS) as well as the formation of nanosized particles inside the biofilm. Also, the presence of Fe in Acidiphilium biofilms was determined by X-ray photoelectron spectroscopy (XPS), whereas surface-enhanced infrared absorption spectroscopy indicated the presence of redox-active proteins.

Biochemical analysis in congenital neuroblastoma.

Objectives: The incidence of congenital neuroblastoma has increased in the recent years. The purpose of this study was to describe the clinical and biochemical characteristics of cases of congenital neuroblastoma diagnosed in our center. Case presentation: We report three cases of congenital neuroblastoma diagnosed in our hospital. In two, diagnosis was made prenatally, whereas the other case was detected in the immediate neonatal period. In the three cases, neuroblastoma was located in the abdominal region and exhibited elevated concentrations of catecholamines or their metabolites in single voided urine samples. Two tumors were classified as stage M, and one as stage L2. The N-MYC oncogen was not amplified in any of the cases studied. Histopathological analysis was favorable in the three cases. The tumor was resected in two patients. The three received chemotherapy. Conclusions: The measurement of catecholamines and their metabolites is essential in the diagnosis of neuroblastoma. When 24 h urine cannot be collected, single voided urine can be used to calculate the index based on creatinine concentrations.

The Effect of Prolonged Pre-Operative Halo Gravity Traction for Severe Spinal Deformities on the Cervical Spine Radiographs.

STUDY DESIGN: Retrospective review of consecutive series. OBJECTIVE: The study sought to assess the effect of prolonged pre-operative halo gravity traction (HGT) on the c-spine radiographs. METHODS: Data of 37 pediatric and adult patients who underwent ≥ 12wks pre-op HGT prior to definitive spine surgery from 2013-2015 at a single site in West Africa was reviewed. Radiographic assessment of the c-spine including ADI, SVA and C2-C7 Lordosis were done at pre HGT and at 4 weekly intervals. Paired T-Test was performed to evaluate changes in these parameters during HGT. RESULTS: 37pts, 18/19 (F/M). Average age 18.2yrs. Diagnoses: 22 idiopathic, 6 congenital, 3 Post TB, 2 NM and 4 NF. Average duration of HGT: 125 days. Baseline coronal Cobb:130 deg, corrected 30% in HGT; baseline sagittal Cobb:146 deg, corrected 32% post HGT. Baseline ADI (3.17 ± 0.63 mm) did not change at 4wks (P > 0.05) but reduced at 8wks (2.80 ± 0.56 mm) and 12wks (2.67 ± 0.51 mm) post HGT (P < 0.05). Baseline HGT SVA (20.7 ± 14.98 mm) significantly improved at 4wks (11.55 ± 10.26 mm), 8wks (7.54 ± 6.78 mm) and 12wks (8.88 ± 4.5 mm) (P < 0.05). Baseline C2-C7 lordosis (43 ± 20.1 deg) reduced at 4wks (26 ± 16.37 deg), 8wks (17.8 ± 14.77 deg) and 12wks (16.7 ± 11.33 deg) post HGT (P < 0.05). There was no incidence of atlanto-axial instability on flexion extension radiographs at any interval. CONCLUSION: Prolonged HGT, while providing partial correction of severe spine deformities, also appeared to have no adverse effect on atlanto-axial stability or cervical alignment. Therefore, HGT can be safely applied for several weeks in the preoperative management of severe spine deformities in pediatric/adult patients.