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.

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.

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.

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.

Axonal Guidance Using Biofunctionalized Straining Flow Spinning Regenerated Silk Fibroin Fibers as Scaffold.

After an injury, the limited regenerative capacity of the central nervous system makes the reconnection and functional recovery of the affected nervous tissue almost impossible. To address this problem, biomaterials appear as a promising option for the design of scaffolds that promote and guide this regenerative process. Based on previous seminal works on the ability of regenerated silk fibroin fibers spun through the straining flow spinning (SFS) technique, this study is intended to show that the usage of functionalized SFS fibers allows an enhancement of the guidance ability of the material when compared with the control (nonfunctionalized) fibers. It is shown that the axons of the neurons not only tend to follow the path marked by the fibers, in contrast to the isotropic growth observed on conventional culture plates, but also that this guidance can be further modulated through the biofunctionalization of the material with adhesion peptides. Establishing the guidance ability of these fibers opens the possibility of their use as implants for spinal cord injuries, so that they may represent the core of a therapy that would allow the reconnection of the injured ends of the spinal cord.

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.

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.

Evaluación y satisfacción del debriefing facilitado por un instructor frente al facilitado por iguales / Assessment and satisfaction regarding the debriefing provided by an instructor vs. the one provided by peers

Objetivo: comparar la evaluación y la satisfacción de las personas participantes del debriefing facilitado por iguales frente al realizado por instructores en simulación clínica de alta fidelidad en un postgrado en Enfermería en Emergencias Extrahospitalarias. Método: estudio cuasiexperimental realizado en 2019 en la Universidad Rey Juan Carlos (Madrid). La población fueron todos los enfermeros matriculados por primera vez. Se asignaron a grupo control (debriefing facilitado por instructoras experimentadas - GC) o grupo intervención (facilitado por iguales a quienes se formó dos horas en debriefing - GI). Tras cada simulación (cuatro en total) se evaluaron los debriefing mediante el cuestionario EDSS© (29 ítems de mín. 1 a máx. 7 puntos) y la satisfacción (mín. 1 a máx. 7 puntos). Se efectuó estadística descriptiva y comparación de los resultados globales de las cuatro sesiones en ambos grupos. Resultados: participaron las 30 personas matriculadas. La evaluación con el cuestionario EDSS© fue similar en ambos grupos, excepto en la capacidad del facilitador para establecer un ambiente de aprendizaje estimulante (GC = 6,61; GI = 6,23; p= 0,019) y en el nivel de conocimientos de este y su empleo para ayudar al participante a mejorar su rendimiento futuro (GC = 6,74; GI = 6,33; p= 0,003). La satisfacción global fue similar en ambos grupos (GC = 6,63; GI = 6,55; p= 0,374). Conclusiones: el debriefing facilitado por un igual supone una alternativa al debriefing tradicional en la formación de enfermeras de postgrado en relación con los resultados de evaluación de participantes y su satisfacción, si bien han de evaluarse también otros aspectos.(AU)

Objective: to compare the assessment and satisfaction by participants for the debriefing provided by peers vs. the one conducted by instructors in a high fidelity clinical simulation at a post-graduate Nursing course on Out-of-Hospital Emergencies. Method: a quasi-experimental study conducted in 2019 at the Universidad Rey Juan Carlos (Madrid). The population consisted in nurses who had been enrolled for the first time. They were assigned to a control arm (debriefing provided by experienced instructors – CA) or an intervention arm (provided by peers who received a 2-hour training on debriefing – IA). After each simulation (four in total) debriefings were assessed through the EDSS© questionnaire (29 items from 1 to 7 scores), and satisfaction (from 1 to 7 scores). Descriptive statistics was conducted as well as comparison for the overall results of the four sessions in both arms. Results: all the 30 persons enrolled participated in the study. The evaluation with the EDSS© questionnaire was similar in both arms, except in the ability of the facilitator to establish a stimulating learning environment (CA = 6.61; IA = 6.23; p= 0.019) and in the level of knowledge of the facilitator and how they used it to help the participants to improve their future performance (CA = 6.74; IA = 6.33; p= 0.003). Overall satisfaction was similar in both arms (CA = 6.63; IA = 6.55; p= 0.374). Conclusions: debriefing facilitated by a peer represents an alternative to traditional debriefing in post-graduate nurse training, based on the evaluation results of participants and their satisfaction; however, other aspects should also be assessed.(AU)

Measuring the elastic modulus of soft biomaterials using nanoindentation.

The measurement of the elastic modulus of soft biomaterials via nanoindentation relies on the accurate determination of the zero-point of the tip-sample interaction on which the depth of penetration into the sample is based. Non-cantilever based nanoindentation systems were originally designed for hard materials, and therefore monitoring the zero-point contact presents a significant challenge for the characterisation of very soft biomaterials. This study investigates the ability of non-cantilever based nanoindentation to differentiate between hydrogels with elastic moduli on the order of single kiloPascals (kPa) using a bespoke soft contact protocol and low flexural stiffness of instrument. Polyethylene glycol (PEG) hydrogels were fabricated as a model system with a range of elastic moduli by varying the polymer concentration and degree of crosslinking. Elastic modulus values were calculated using the Oliver-Pharr method, Hertzian contact model, as well as a viscoelastic model to account for the time-dependent behaviour of the gels. The stiffness measurements were validated by measuring cantilever beams with the equivalent flexural stiffness to that of the PEG hydrogels being tested. The results demonstrated a high repeatability of the measurements, enabling differentiation between hydrogels with elastic moduli in the single kPa to hundreds of kPa range.

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.

Carcinoma pseudopapilar sólido del páncreas / Solid pseudo-papillary carcinoma of the pancreas

El tumor sólido pseudopapilar del páncreas, conocido también como tumor de Frantz, es una enfermedad rara: neoplasia bien delimitada, de lento crecimiento, no agresiva pero maligna, habitualmente con pronóstico favorable. El tratamiento de elección es quirúrgico. Aunque algunos de ellos son agresivos a nivel local, la mayoría de los pacientes se curan con la resección completa del tumor. Se reportó el caso de una mujer de 30 años, ingresada en el Servicio de Cirugía General del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, con diagnóstico presuntivo clínico e imagenológico, de tumor pseudopapilar sólido del páncreas, con confirmación histológica tras la resección quirúrgica. Este infrecuente tumor debe ser considerado en el diagnóstico diferencial de los tumores pancreáticos, fundamentalmente en mujeres jóvenes(AU)

The solid pseudo-papillary carcinoma, also known as Frantz´s tumor, is a rare disease. It is a well-defined neoplasia, of low growth, non-aggressive but malignant, usually with a favorable prognosis. The elective treatment is the surgery. Although some of them are locally aggressive, most patients are healed with the complete tumor resection. The authors reported the case of a woman, aged 30 years who entered the Service of General Surgery of the University Hospital Comandante Faustino Pérez Hernández, with a presumptive clinical and imaging diagnosis of pancreas solid pseudo-papillary tumor, histologically confirmed after surgical resection. This infrequent tumor should be taken into account in the differential diagnosis of pancreatic tumors, mainly in young women(AU)

One-stage multiple posterior column osteotomies and fusion and pre-op halo-gravity traction may result in a comparative and safer correction of complex spine deformity than vertebral column resection.

STUDY DESIGN: A retrospective review of prospectively collected from patients recruited at a single center. PURPOSE: To test whether safe and optimal correction can be obtained with preoperative halo-gravity traction and posterior spinal fusion with adjunctive procedures but without VCR. Posterior vertebral column resection(VCR) is gaining popularity for correction of severe spinal deformity. However, it is a highly technically demanding procedure with potential risk for complications and neurological injury. METHODS: In total, 72 patients with severe spinal deformity (Cobb angle > 100º) who underwent HGT followed by definitive PSF with PCO, with or without concave rib osteotomy and thoracoplasty. Demographic and surgical data were collected. Conventional coronal and sagittal radiographic measurements were obtained pre-traction, post-traction, post-op and at follow-up to determine the final deformity correction. Postoperative neurological and major complications were reviewed. We used Chi-square to compare proportion between groups and t test to compare groups in quantitative/ordinal variables. RESULTS: There were 72 patients (35 females, 37 males). The etiology was congenital (21),idiopathic (45), neurofibromatosis (2) and neuromuscular (4). The mean was: age 18 ± 4.6 years; duration of HGT 103 ± 35 days; coronal Cobb angle before traction 131.5 ± 21.4º vs 92. ± 15.9º after HGT (30% correction) and 72.8 ± 12.7º after fusion (47% correction); kyphosis angle before traction 134.7 ± 32.3º vs 97.1 ± 22.4º after HGT and 73.7 ± 21.3º post-fusion. Number of fusion levels 14 ± 1; EBL 1730 ± 744 cc; number of PCOs done 5 ± 2; number of concave rib osteotomies (2 ± 2). There were 16 patients with postoperative complications (22.2%), 10 medical, one wound infection, 2 implant related and 3 post-op neuro-deficits (all of whom recovered at follow-up). There was one death (cardiac arrest). CONCLUSION: HGT and one-stage posterior fusion with PCO, with or without concave rib resection and thoracoplasty, without VCR, achieved satisfactory correction of rigid complex spine deformity with minimal neurological complications. The results compare favorably with previous reports of similar deformities treated with VCR. LEVEL OF EVIDENCE: III.

Tratamiento quirúrgico paliativo de los tumores periampulares, una opción de paliación a largo plazo / Palliative surgical treatment of periampullary tumors, an option of long-term palliation

RESUMEN Introducción: los tumores de la encrucijada duodeno-bilio-pancreática o periampulares corresponden a un grupo heterogéneo de tumores. Se originan dentro de los 2 cm de la papila duodenal mayor. En los tumores irresecables, el tratamiento debe estar dirigido a la paliación más efectiva. El tratamiento quirúrgico paliativo va dirigido a resolver la obstrucción biliar, duodenal y el dolor, con el fin de optimizar la calidad de vida de los pacientes. Objetivo: describir el comportamiento del tratamiento quirúrgico paliativo de los tumores periampulares. Materiales y métodos: se realizó una investigación observacional, descriptiva y prospectiva con los pacientes con tumor periampular irresecable tributarios a tratamiento quirúrgico paliativo, en el Servicio de Cirugía General del Hospital Universitario "Comandante Faustino Pérez Hernández", en la ciudad de Matanzas, desde enero del 2010 hasta diciembre del 2019. Resultados: el tumor de páncreas fue el más representado. Todos los pacientes fueron tributarios de derivación biliar quirúrgica paliativa, sin embargo, la derivación gástrica se realizó solo con confirmación endoscópica de infiltración tumoral u obstrucción duodenal y la esplacnicectomía química, siempre que fue factible técnicamente o las condiciones del paciente lo permitieron. La hepaticoyeyunostomía en Y de ROUX fue la derivación biliar de elección. La principal complicación quirúrgica fue la sepsis provocando las muertes. Conclusiones: la paliación quirúrgica es la alternativa de elección con mejores resultados a largo plazo, en los tumores periampulares irresecables con buen estado general, lo que contribuye a una mejor calidad de vida (AU).

ABSTRACT Introduction: the tumors of the duodenal-biliary-pancreatic junction or periampullary tumors correspond to a heterogeneous group of tumor. They originate inside the 2 cm of the major duodenal papilla. In unresectable tumors, the treatment should be intended for the most effective palliation. The surgical palliative treatment is intended for solving biliary, duodenal obstruction, and pain, with the aim of optimizing patients' life quality. Objective: to describe the behavior of the periampullary tumors palliative surgical treatment. Materials and methods: a prospective, descriptive, observational research was carried out in patients with unresectable periampullary tumor tributary to palliative surgical treatment, in the Service of General Surgery of the University Hospital "Comandante Faustino Perez Hernandez", of Matanzas, from January 2010 to December 2019. Results: pancreas tumor was the most represented one. All patients were tributary to biliary palliative surgical derivation, however, gastric derivation was performed only with endoscopic confirmation of tumor infiltration or duodenal obstruction, and chemical splanchnicectomy whenever it was technically feasible and the patient's conditions allowed it. Roux's Y-shaped hepaticojejunostomy was the elective biliary derivation. The main surgical complication was sepsis provoking deaths. Conclusions: surgical palliation is the election alternative with long- term better outcomes, in unresectable periampullary tumors with a good general status, contributing to better life quality (AU).

Colangiocarcinoma, diagnóstico, tratamiento y evolución clínica. Presentación de un caso con sobrevida 5 años / Cholangiocarcinoma: diagnosis, treatment and clinical evolution. Presentation of a case with five-year survival

RESUMEN El colangiocarcinoma es un tumor maligno originado en el epitelio de los conductos biliares intra o extrahepáticos. En el cuadro clínico destacan el dolor en hipocondrio derecho, ictericia y baja de peso. Actualmente, el diagnóstico se ha facilitado por la disponibilidad de variados procedimientos imagenológicos y endoscópicos. Se presentó un caso al que se le realizó el diagnóstico de este tipo de tumor. Se sometió a tratamiento endoscópico, quirúrgico y oncológico con Gemcitabina, Cisplatino y Oxaliplatino. Fue seguido por equipo multidisciplinario y evolucionó con sobrevida de 5 años (AU).

ABSTRACT Cholangiocarcinoma is a malignant tumor originated in the epithelium of the intra or extra hepatic biliary ducts. Pain in the right hypochondrium, jaundice and low weight are the main clinical features. Currently, the diagnosis has been facilitated by the availability of different imaging and endoscopic procedures. The authors presented a case diagnosed with this kind of tumor. The patient underwent surgical, endoscopic and oncologic treatment with gemcitabine, cisplatine and oxaliplatine. He was followed up by a multidisciplinary team and evolved with five-year survival (AU).

Characterization of complex vertebral transposition (gamma deformity) > 180 degrees: clinical and radiographic outcomes of halo gravity traction and vertebral column resection (VCR).

STUDY DESIGN: Prospective case series OBJECTIVE: Results of surgical treatment of complex vertebral transposition "Gamma Deformity" > 180 degrees with halo gravity traction (HGT) and vertebral column resection (VCR). We recently published a novel classification system for complex spine deformities of which complex vertebral transposition > 180 degrees (Gamma; type 3) was described. Halo gravity traction (HGT) has been shown to mitigate surgical risk in complex spine deformity correction and in some cases obviates the need for three-column osteotomy. However, we are not aware of report of its utilization in treating Gamma deformities with or without vertebral column resection (VCR). METHODS: A consecutive series of 13 patients with Gamma deformity (GD) were prospectively enrolled at a single site in West Africa. Standard radiographs and 3D computerized tomography (CT) were done to assess coronal and sagittal vertebral transposition (CVT and SVT). The HGT with 50% of body weight was applied over several weeks followed by VCR. Demographics, operative data, radiographic parameters, and complications data were collected. RESULTS: 13 pts with GD underwent HGT for an avg of 110 days prior to definitive surgery. Etiologies were Congenital-11 pts and Neurofibromatosis-2 pts. Average age: 17.8 years; Pts were reviewed at 3 months post-op and at minimum 2-year follow-up. Preop myelopathy was present in five patients. Pre-op CVT avg 75% and was corrected in all cases post-op. SVT avg 211 deg and improved with HGT by 36% and corrected to 53 deg (74% correction) post-op. Thoracic kyphosis avg -42 deg and averaged 48 deg post-op. Intra-op spinal cord monitoring (SCM) alerts occurred in 8 pts (61%). Post-operative LEM deficits occurred in 5 pts: 2 fully recovered by 3 months and 2 year follow-up, while the remaining 3 improved but had residual motor deficits at final follow-up. There was one post-operative mortality. CONCLUSION: The management of complex vertebral transposition (Gamma deformity) > 180 degrees with HGT prior to VCR is not only effective in some patients, but also associated with high SCM alerts and neurologic injury rates. Myelopathic patients with thoracic deformities are at higher risk of developing permanent neurologic deficits. Surgeons should be aware of this rare and unusual deformity and consider HGT and VCR bearing in mind the technical challenges and high complication rate.

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.