Measuring the Delay in the Referral of Unstable Vertebral Metastasis to the Spine Surgeon: A Retrospective Study in a Latin American Institution.

Background: The delay in the referral of patients with potential surgical vertebral metastasis (VM) to the spine surgeon is strongly associated with a worse outcome. The spinal instability neoplastic score (SINS) allows for determining the risk of instability of a spine segment with VM; however, it is almost exclusively used by specialists or residents in neurosurgery or orthopedics. The objective of this work is to report the delay in surgical consultation of patients with potentially unstable and unstable VM (SINS >6) at our center. Material: We performed a 5-year single-center retrospective analysis of patients with spine metastasis on computed tomography (CT). Patients were divided into Group 1 (G1), potentially unstable VM (SINS 7-12), and Group 2 (G2), unstable VM (SINS 13-18). Time to surgical referral was calculated as the number of days between the report of the VM in the CT and the first clinical assessment of a spinal surgeon on the medical records. Results: We analyzed 220 CT scans, and 98 met the selection criteria. Group 1 had 85 patients (86.7%) and Group 2 had 13 (13.3%). We observed a mean time to referral of 83.5 days in the entire cohort (std = 127.6); 87.6 days (std = 135.1) for G1, and 57.2 days (std = 53.8) for G2. The delay in referral showed no significant correlation with the SINS score. Conclusion: We report a mean delay of 83.5 days in the surgical referral of VM (SINS >6, n = 98). Both groups showed cases of serious referral delay, with 25% of patients having the first surgical consultation more than three months after the CT study.

Testicular yolk sac tumour metastasis to the L2 vertebra.

The role of surgery for metastases to the vertebra from yolk sac tumours has not been established. The main treatment for disseminated disease is chemotherapy. We present a man in his 30s with a left orchiectomy for a testicular mixed germ cell tumour with a prominent yolk sac component who, 12 months later, developed an asymptomatic metastasis to the L2 vertebra unresponsive to chemotherapy and radiotherapy. The patient underwent resection of the L2 vertebral body, leaving a small residual tumour anterior to the vertebra attached to the great vessels. Pathology confirmed the diagnosis of a metastatic testicular yolk sac tumour in the vertebra. The postoperative MRI 6 months later demonstrated significant expansion of the tumour at the soft tissues anterior to the expandable titanium cage encasing the great vessels and extending to the paraspinal areas. Additional salvage surgery was not recommended because of the advanced stage of the tumour.

Correlation between the Severity of the Lumbar Degenerative Disease and Sagittal Spinopelvic Alignment / Correlação entre a gravidade da doença degenerativa lombar e o alinhamento espinopélvico

Abstract Objective To evaluate the impact of the severity of lumbar degenerative disease (LDD) on sagittal spinopelvic alignment. Methods In total, 130 patients (mean age: 57 years; 75% female) with LDD-associated low-back pain were prospectively included. The severity of the LDD was defined by the following findings on anteroposterior and lateral lumbar spine radiographs: osteophytosis; loss of of height of the intervertebral disc; terminal vertebral plate sclerosis; number of affected segments; deformities; and objective instability. The disease was classified as follows: grade 0-absence of signs of LDD in the lumbar spine; grade I - signs of LDD in up to two segments; grade II - three or more segments involved; grade III - association with scoliosis, spondylolisthesis, or laterolisthesis. Spinopelvic radiographic parameters, including pelvic incidence (PI), lumbar lordosis (LL), discrepancy between the PI and LL (PI-LL), pelvic tilt (PT), and sagittal vertical axis (SVA), were analyzed according to the LDD grades. Results The radiographic parameters differed according to the LDD grades; grade-III patients presented higher SVA (p= 0.001) and PT (p= 0.0005) values, denoting greater anterior inclination of the trunk and pelvic retroversion when compared to grade-0 andgrade-I subjects. In addition, grade-III patients had higher PI-LL values, which indicates loss of PI-related lordosis, than grade-I subjects (p= 0.04). Conclusion Patients with more severe LDD tend to present greater spinopelvic sagittal misalignment compared to patients with a milder disease.

Resumo Objetivo Avaliar o impacto da graduação da doença degenerativa lombar (DDL) sobre o alinhamento sagital espinopélvico. Métodos Ao todo, 130 pacientes (dade média: 57 anos; 75% do sexo feminino) com dor lombar associada a DDL foram prospectivamente incluídos. A gravidade da DDL foi definida pelos seguintes achados nas radiografias anteroposterior e de perfil da coluna lombar: osteofitose; perda de altura do disco intervertebral; esclerose na placa vertebral terminal; número de segmentos afetados; deformidades; e instabilidade objetiva. Os pacientes foram graduados segundo a DDL da seguinte maneira: grau 0-ausência de sinais de DDL na coluna lombar; grau I - sinais de DDL em até dois segmentos; grau II - envolvimento em três ou mais segmentos; grau III - quando associada a escoliose, espondilolistese ou laterolistese. Parâmetros radiográficos espinopélvicos, como incidência pélvica (IP), lordose lombar (LL), discrepância entre a IP e a LL (IP-LL), versão pélvica (VP), e eixo vertical sagital (EVS) foram analisados de acordo com os graus de DDL. Resultados Houve diferença nos parâmetros radiográficos comparando-se os graus de DDL, com os pacientes de grau III apresentando maiores valores de EVS (p= 0,001) e VP (p= 0,0005), o que denota maior inclinação anterior do tronco e maior retroversão pélvica do que os pacientes de graus 0 e I. Pacientes de grau III também apresentaram maiores valores de IP-LL, o que denota perda da lordose relativa ao valor da IP, do que pacientes grau I (p= 0,04). Conclusão Pacientes com DDL mais grave demonstraram uma tendência a maior desalinhamento sagital espinopélvico comparados com pacientes com graus mais leves.

Effectiveness of Fluoroscopy-Guided Percutaneous Vertebral Biopsy / Eficácia da biópsia vertebral percutânea guiada por fluoroscopia

Abstract Objective To define the effectiveness of fluoroscopy-guided percutaneous vertebral biopsy. Methods Prospective study of patients with vertebral destruction syndrome at one institution. Percutaneous transpedicular vertebral biopsies guided by fluoroscopy were performed, and bony tissue and intervertebral disc tissue were extracted; histopathology and microbiology studies were also performed. Age, sex, vertebral segment, neurologic status, and biopsy and culture results were analyzed. Results The average age of the patients was 53.8 years (range: 2 to 83 years), and the main spine segment was the lumbar segment in 62% of the cases. According to the impairment scale of the American Spinal Injury Association (ASIA), preoperatively, 49% of the patients were classified as Asia E, and 100% had pain. Definitive etiology was identified in 83% of the sample. The etiology was grouped into three categories: infectious, neoplasia, and degenerative (osteoporotic). The infectious group was composed of 36% of the patients, in whom Staphylococcus aureus was the most common agent identified; in 34.9% the sample, the etiology was neoplastic, most commonly multiple myeloma and metastatic disease due to prostate cancer; 21.7% of the patients had osteoporosis. The average surgical time was of 47.5 minutes, the average blood loss was of 10 mL. No complications were reported. Conclusion Transpedicular percutaneous biopsy guided by fluoroscopy had an effectiveness of 83% for the etiological diagnosis of vertebral destruction syndrome in the present series. It should be considered a useful minimally-invasive procedure, which is easy, economical, and reproducible, with low risk of short- and long-term complications.

Resumo Objetivo Definir a eficácia da biópsia vertebral percutânea guiada por fluoroscopia. Métodos Este é um estudo prospectivo de pacientes com síndrome de destruição vertebral em uma instituição. Os pacientes foram submetidos a biópsias vertebrais transpediculares percutâneas guiadas por fluoroscopia, com obtenção de tecido ósseo e tecido do disco intervertebral, para estudo histopatológico e microbiológico. Idade, sexo, segmento vertebral, estado neurológico, e resultados de biópsia e de cultura foram analisados. Resultados A idade média dos pacientes foi de 53,8 anos (gama: 2 a 83 anos), e o principal local acometido da coluna foi a segmento lombar, em 62% dos casos. Segundo a escala de disfunção da American Spinal Injury Association (ASIA), no pré-operatório, 49% dos pacientes foram classificados como ASIA E, e 100% apresentavam dor. A etiologia definitiva foi identificada em 83% dos pacientes. A etiologia foi agrupada em três categorias: infecciosa, neoplásica, e degenerativa (osteoporótica). O grupo infeccioso era composto por 36% dos pacientes da amostra, e Staphylococcus aureus foi o agente mais comumente identificado; em 34,9% dos casos, a etiologia era neoplásica, principalmente mieloma múltiplo e doença metastática por câncer de próstata; 21,7% dos pacientes apresentavam osteoporose. O tempo cirúrgico médio foi de 47,5 minutos, e a perda média de sangue foi de 10 mL. Nenhuma complicação foi relatada. Conclusão Nesta série, a biópsia percutânea transpedicular guiada por fluoroscopia teve 83% de eficácia no diagnóstico etiológico da síndrome de destruição vertebral. Este procedimento minimamente invasivo deve ser considerado bom, fácil, barato e reprodutível, com baixo risco de complicações em curto e longo prazos.

Petroclival intravascular papillary endothelial hyperplasia with psammoma body-like structures.

Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH) is considered a non-neoplastic lesion. It is probably an unusual exaggerated reorganization of a thrombus. IPEH may be present as a secondary lesion in hemangiomas. Symptomatic osseous hemangiomas are rare tumors. Few cases of clival and petrous bone hemangiomas have been described. None of them shows secondary IPEH. So far, there are only four reported cases of cranial bone IPEHs in the literature, two in the skull, one in the clivus and one in the petrous apex. The aim of this study is to report an additional case of osseous hemangioma with secondary IPEH of the petroclival region. We review the literature and describe the main clinical features of IPEHs and hemangiomas of the clivus and the petrous bone. Additionally, we report an unusual histological feature observed in our case of IPEH, the presence of psammoma body-like structures. This feature has been rarely mentioned previously in IPEH. We consider that IPEH should be included in the lesions that may present psammoma bodies to avoid misdiagnosing it as a tumor that commonly shows psammoma bodies, such as intraosseous meningioma or, less frequently, metastasis of thyroid or ovarian carcinoma.

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain.

PURPOSE: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). METHODS: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. RESULTS: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). CONCLUSION: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

Association of thoracic spine deformity and cardiovascular disease in a mouse model for Marfan syndrome.

AIMS: Cardiovascular manifestations are a major cause of mortality in Marfan syndrome (MFS). Animal models that mimic the syndrome and its clinical variability are instrumental for understanding the genesis and risk factors for cardiovascular disease in MFS. This study used morphological and ultrastructural analysis to the understanding of the development of cardiovascular phenotypes of the the mgΔloxPneo model for MFS. METHODS AND RESULTS: We studied 6-month-old female mice of the 129/Sv background, 6 wild type (WT) and 24 heterozygous animals from the mgΔloxPneo model. Descending thoracic aortic aneurysm and/or dissection (dTAAD) were identified in 75% of the MFS animals, defining two subgroups: MFS with (MFS+) and without (MFS-) dTAAD. Both subgroups showed increased fragmentation of elastic fibers, predominance of type I collagen surrounding the elastic fiber and fragmentation of interlaminar fibers when compared to WT. However, only MFS animals with spine tortuosity developed aortic aneurysm/dissection. The aorta of MFS+ animals were more tortuous compared to those of MFS- and WT mice, possibly causing perturbations of the luminal blood flow. This was evidenced by the detection of diminished aorta-blood flow in MFS+. Accordingly, only MFS+ animals presented a process of concentric cardiac hypertrophy and a significantly decreased ratio of left and right ventricle lumen area. CONCLUSIONS: We show that mgΔloxPneo model mimics the vascular disease observed in MFS patients. Furthermore, the study indicates role of thoracic spine deformity in the development of aorta diseases. We suggest that degradation of support structures of the aortic wall; deficiency in the sustenance of the thoracic vertebrae; and their compression over the adjacent aorta resulting in disturbed blood flow is a triad of factors involved in the genesis of dissection/aneurysm of thoracic aorta.

Efectos del ranelato de estroncio sobre la densidad mineral ósea en hombres / Effect of strontium ranelate on bone mineral density in men

La osteoporosis afecta al 6-7% de la poblaciónmasculina. Es alta la proporción de pacientes confractura osteoporótica sin diagnóstico previo de estaenfermedad. La mortalidad luego de una fracturaes mayor en hombres que en población femenina;a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son:bifosfonatos, teriparatida y ranelato de estroncio. Elobjetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea enhombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67.8±3.0 años,tratados con ranelato de estroncio (2 g/día) durante 1año. Todos los pacientes presentaban un T-score inferior a -2.5 en cadera o columna vertebral o un T-scoreinferior a -2.0 y factores de riesgo de fractura. Nohubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico,parathormona, 25(OH)vitamina D, fosfatasa alcalinay desoxipiridinolina). Luego de 1 año de tratamiento con ranelato de estroncio se observó incrementode la densidad mineral ósea en columna lumbar:0.953±0.029 versus 0.997±0.030 g/cm2 (p=0.0068),cuello femoral: 0.734±0.013 versus 0.764±0.016 g/cm2 (p=0.0084) y cadera total: 0.821±0.02 versus0.834±0.02 g/cm2 (p=0.0419). Conclusión: luego de1 año de tratamiento el ranelato de estroncio produjoun incremento significativo de la densidad mineralósea en columna lumbar y fémur proximal en hombres con osteoporosis (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higherin men than in women; in spite of this, mostpatients are left without treatment for osteoporosis. Drugs approved, for the treatment ofosteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR).The objective of this study was to evaluate theeffect of SrR on axial BMD in men after one yearof treatment. We obtained pertinent data frommedical registries of 20 men aged 67,8±3,0 years,treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hipor the lumbar spine, or a T-score below -2,0and one or more risk factors for fracture. Thelevels of serum calcium, phosphate, alkalinephosphatase, 25-hydroxyvitamin D, or PTH,or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there weresignificant increases in BMD at the lumbarspine: 0,953±0,029 versus 0,997±0,030 g/cm2(p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2(p=0,0419). Conclusion: in osteoporotic men,treatment with SrR significantly increases BMDin the lumbar spine and the proximal femur (AU)

Spondyloarthropathy in vertebrae of the aquatic Cretaceous snake Lunaophis aquaticus, and its first recognition in modern snakes.

Inflammatory arthritis is documented for the first time in snakes. Ossification of the intervertebral capsule and zygapophyseal joints resulting in segmental vertebral fusion was observed in the aquatic Cretaceous snake Lunaophis aquaticus. Such pathologic alterations are pathognomonic for the spondyloarthropathy form of inflammatory arthritis. A survey of 2144 snakes in recent collections, performed to identify Holocene prevalence, revealed only two occurrences in extant snakes. The findings in Bitis gabonica and Elaphe taeniura were indistinguishable from those noted in Lunaophis aquaticus and identical to those previously recognized in modern varanids. The pathology likely represents a form of reactive arthritis related to enteropathic infection. While the disease probably did not affect general locomotion, its vertebral column position may have compromised mating.

Accelerated Pubertal Tempo in a 46,XY Aromatase-Deficient Patient.

BACKGROUND: Aromatase deficiency is a rare autosomal recessive disorder. 46,XY-affected patients often remain undiagnosed until late puberty. Only 2 pediatric cases have been reported. Data on pubertal development in affected males are scarce. AIM: To report the clinical phenotype and hormonal studies of an aromatase-deficient boy during the prepubertal and early pubertal period. RESULTS: The patient was the older brother of a 46,XX girl with aromatase deficiency. Molecular analysis revealed a previously reported homozygous mutation (Arg192Cys) in the CYP19A1 gene. Pubertal onset was at 9.8 years. At 11.3 years of age, signs of rapidly progressive puberty were seen. Laboratory tests revealed normal pubertal basal and GnRH-stimulated gonadotropin levels, normal Sertoli cell markers, and increased testosterone. The prepubertal lumbar spine bone mineral density (BMD) was normal but pubertal bone mineral accrual was incomplete, leading to osteopenia. CONCLUSION: Estrogen restraint on gonadotropin secretion has been demonstrated in animal and human models. Interestingly, our patient presented with accelerated puberty and apparently normal pituitary gonadal function. These findings suggest that aromatase activity may be required to define pubertal progression in boys. Estrogen deficiency due to aromatase deficiency is responsible for insufficient bone mineral accrual during puberty.

A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy.

BACKGROUND: Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. METHODS: Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. RESULTS: Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. CONCLUSION: Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma.

Genetic diversity and antimicrobial resistance profile of Enterococcus faecalis isolated from broilers with vertebral osteomyelitis in Southeast Brazil.

Vertebral osteomyelitis (VO) is a worldwide emerging disease that affects broilers. Recently, the isolation of Enterococcus faecalis in cases of the disease has been described. This study aimed at determining the genetic diversity and antimicrobial resistance profile of 12 E. faecalis strains isolated from broilers with VO. Strains were isolated from nine flocks from six farms in a high-density poultry production area in Southeast Brazil and were evaluated using multilocus sequence typing and phylogenetic analysis. Antimicrobial susceptibility tests and PCR were performed to detect antimicrobial resistance genes. E. faecalis isolates belonged to different sequence types (ST), six of which (ST49, ST100, ST116, ST202, ST249, and ST300) have been previously described. Strains ST708 and ST709 were newly identified in this study. Strain ST49 was most frequently isolated (50% of the flocks) from the analysed VO cases. No phylogenetic or phylogeographic relationship was found among the strains. The VO isolated E. faecalis strains showed highest resistance to aminoglycosides, mainly gentamicin (40%), but were highly susceptible to vancomycin (10%). Aminoglycoside resistance genes were detected in seven E. faecalis strains, and AAC6'-APH2″ genes were most frequently detected. The results showed that E. faecalis strains isolated from recently reported VO cases were highly diverse genetically. The diversity of genotypes in circulation in the analysed flocks, without apparent relationship among them, raises questions on aetiopathogenesis of the disease in broilers and evolutionary aspects of E. faecalis.

Spine and Thoracic Height Measurements Have Excellent Interrater and Intrarater Reliability in Patients With Early Onset Scoliosis.

STUDY DESIGN: Reproducibility of measurements. OBJECTIVE: This study investigates the reliability and standard error of measurement of spine and thoracic height radiographic measurements in patients with early onset scoliosis (EOS). SUMMARY OF BACKGROUND DATA: Spine and thoracic height radiographic measurements are often used as a surrogate for pulmonary development in patients with EOS. There is limited literature validating the reliability of spine and thoracic height measurements in the EOS population. METHODS: Using pilot data, we determined measuring 49 unique radiographs would provide 80% power to obtain a 95% confidence interval (CI) width of 0.05 for the interclass correlation coefficients (ICCs). A random sampling strategy, stratified by underlying diagnosis from the Classification of Early Onset Scoliosis (C-EOS), was used to distribute the diagnoses in the study sample. Two attending pediatric spine surgeons, two pediatric orthopedic fellows, and two research assistants measured coronal spine (T1-S1) and thoracic (T1-T12) height on digital radiographs using imaging software (Surgimap; Nemaris, Inc, New York) on two separate occasions at least 3 weeks apart. Order of images was randomized for the second iteration. Linear mixed model regression analyses were used to estimate interrater and intrarater reliability. RESULTS: The study sample included subjects (N = 48) with idiopathic (N = 17, 35%), congenital (N = 16, 33%, 1 patient excluded), neuromuscular (N = 11, 23%), and syndromic (N = 4, 8%) scoliosis. Overall interrater reliability estimates for spine height (ICC: 0.894, 95% CI: 0.847-0.932) and thoracic height (ICC: 0.890, 95% CI: 0.844-0.929) were excellent. Intrarater reliability estimates for spine height (ICC: 0.906, 95% CI: 0.830-0.943) and thoracic height (ICC: 0.898, 95% CI: 0.817-0.938) were also excellent. CONCLUSION: There is excellent interrater and intrarater reliability for radiographic measurements of spine and thoracic height in the EOS population at our institution. LEVEL OF EVIDENCE: 2.

Spondylolysis in the past: A case study of hunter-gatherers from Southern Patagonia.

Spondylolysis is a fracture of the pars interarticularis, the portion of the neural arch that lies between the superior articular facets and the inferior articular facets. Clinical evidence has suggested repetitive trauma to be the most probable cause, even though morphological weakness of the vertebra is probably also involved. Prevalence is between 3% and 8% in modern populations, while in archaeological samples it varies from 0% to 71.4%. Considering that very little data about this condition is available in past populations from the southern extreme of South America, the aim of this paper is to analyze the spondylolysis in a human skeletal sample from Southern Patagonia and, at the same time, to explore the prevalence of spondylolysis in archaeological contexts around the world to gain a better understanding of the results presented here. The Southern Patagonian skeletal series analyzed here showed a prevalence of 20%, with lower prevalence in the pre contact sample (11.1%) than in the contact period (23.1%). Skeletons from the Salesian Mission "Nuestra Señora de La Candelaria" showed a higher prevalence (25%) than the sample of skeletal remains recovered from outside the mission (20%), suggesting that changes in lifestyle of hunter-gatherers during contact could be implicated in the development of spondylolysis in this sample. A worldwide survey displays a wide range of prevalence figures in American and Asian samples and low diversity between African and European populations. Hunter-gatherers from Southern Patagonia showed similar values to those observed in other American samples.

Los sistemas de descompresión vertebral tienen origen en los estudios realizados por los científicos de la NASA, quienes observaron que los astronautas que tenían dolor de espalda en tierra al subir al espacio, con la ingravidez, les desaparecía el dolor. [Editorial] / The vertebral decompression systems have their origin in the studies carried out by the NASA scientists, who observed that astronauts who had back pain on earth when going up into space, with weightlessness, the pain disappeared. [Editorial]

Los sistemas de descompresión vertebral tienen origen en los estudios realizados por los científicos de la NASA, quienes observaron que los astronautas que tenían dolor de espalda en tierra al subir al espacio, con la ingravidez, les desaparecía el dolor. Con estos antecedentes, el científico canadiense Dr. Alan E. Dyer (médico que inventó y patentó el desfibrilador cardiaco) consiguió recrear este escenario espacial en tierra, patentando una fórmula logarítmica que conseguía tratar aisladamente cada vértebra aplicando una secuencia de tracción controlada, progresiva e indolora sobre la columna vertebral. Estos sistemas de descompresión vertebral están basados en el método clásico de tracción, adaptado a la tecnología moderna. No tracciona, sino que descomprime los discos y las pequeñas articulaciones facetarias de forma progresiva e indolora, utilizando un software que aplica una fuerza de intensidad variable para cada tipo de paciente. Los ordenadores constituyen el "cerebro" que se encarga de controlar y ejecutar el software de la unidad de descompresión; siendo el "corazón" un dispositivo electromecánico que con el propio procesador acciona el servomotor que pone en marcha el sistema.

Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants. METHODS: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life. RESULTS: Across all 3 cohorts, 89 infants had radiographs performed at either time point, and 85 had radiographs performed at both time points. Metaphyseal lucency was present in 1 case in Brazil and 2 in Malawi. Fifteen percent of infants from Brazil and 9% of infants from Malawi presented bone age discrepancies. No other abnormalities were identified in Brazil, whereas in Malawi, there were 7 more cases of wrist osteopenia, 2 of spine osteopenia and 3 other abnormalities. CONCLUSION: Bone abnormalities were not uncommon in the overall cohort of HIV-exposed infants. Because of very limited study drug exposure at the time of birth, it is unlikely that TDF was associated with these findings. Untreated maternal HIV disease and/or maternal nutritional status could potentially be related to fetal bone development. This association should be explored in future cohort studies.

IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated. Recent studies showed that RTT-derived neurons have many cellular deficits when compared to control, such as: less synapses, lower dendritic arborization and reduced spine density. Interestingly, treatment of RTT-derived neurons with Insulin-like Growth Factor 1 (IGF1) could rescue some of these cellular phenotypes. Given the critical role of IGF1 during neurodevelopment, the present study used human induced pluripotent stem cells (iPSCs) from RTT and control individuals to investigate the gene expression profile of IGF1 and IGF1R on different developmental stages of differentiation. We found that the thyroid hormone receptor (TRalpha 3) has a differential expression profile. Thyroid hormone is critical for normal brain development. Our results showed that there is a possible link between IGF1/IGF1R and the TRalpha 3 and that over expression of IGF1R in RTT cells may be the cause of neurites improvement in neural RTT-derived neurons.

Frequency and Risk Factors for Additional Lesions in the Axial Spine in Subjects With Chordoma: Indications for Screening.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aim to evaluate the frequency and clinical significance of additional lesions in the axial spine in subjects with chordoma and to assess the need for screening. SUMMARY OF BACKGROUND DATA: Chordomas are rare tumors that may be multicentric or metastasize and affect several bones in the axial spine. The incidence of multiple lesions in the axial spine is unknown. Understanding the incidence rate of multiple lesions in the spine in subjects with chordomas will help guide utilization of total spine screening imaging. METHODS: We performed a retrospective review of medical records of 42 subjects with histologically confirmed chordomas who had complete imaging of the axial spine. Lesions with imaging characteristics suggestive of chordomas/notochordal remnants were identified. Data on age at diagnosis, sex, size (in maximal dimension), type of chordoma (conventional, chondroid, or dedifferentiated), and whether pulmonary metastases were present were recorded. Binomial two-sample tests of proportions were used to compare proportions. Logistic regression was used to assess predictors of additional lesions. RESULTS: Forty-two subjects (57.1% male) were identified. The proportion of subjects with additional lesions in the axial spine was 16.7% (7/42). Age, sex, size, and subtype of chordoma were not significant predictors of having additional lesions (P > 0.05 for each variable). However, having pulmonary metastases was a significant predictor of having additional lesions (P < 0.05). CONCLUSION: Approximately 17% of subjects with chordomas had additional lesions in the axial spine. It is unclear whether these represent metastases, synchronous primary chordomas or notochordal remnant tissue. Screening imaging of the axial spine may reveal additional lesions in particular in subjects with pulmonary metastases. LEVEL OF EVIDENCE: 3.

Nusinersen / Nusinersen

INTRODUCCIÓN: La atrofia muscular espinal es una enfermedad neuromuscular hereditaria caracterizada por la afectación de las células del asta anterior de la médula espinal (neuronas motoras), que cursa con debilidad proximal simétrica y atrofia progresiva de los grupos musculares. Presenta una incidencia mundial descrita entre 1/6.000 y 1/10.000 nacimientos y una tasa de portadores entre 1/35 y 1/50. Es un trastorno autosómico recesivo causado por la alteración (ausencia o mutación) en el gen Survival Motor Neuron 1 (SMN1), localizado en la región cromosómica 5q13. El locus AME está duplicado y en la parte más centromérica de este locus existe un gen homólogo conocido como Survival Motor Neuron 2 (SMN2). Mientras el gen SMN1 está siempre alterado en los pacientes y es considerado el determinante de la enfermedad, el gen SMN2 está siempre presente en número de 1 a 5 copias en los afectados. Cuantas más copias de SMN2 haya, en general será más benigno el fenotipo, por lo que se considera al gen SMN2 como un modificador fenotípico. El gen SMN1 produce aproximadamente el 100% de un transcripto y consecuentemente su proteína, que son completos y funcionantes. Mientras que el gen SMN2 genera un 50% de transcriptos que son completos y funcionantes, mientras el 50% restante no lo son. Esta disminución de la cantidad de proteína SMN en las neuronas motoras las hace más sensibles y proclives a su degeneración y muerte. La AME se clasifica en cuatro grupos sobre la base de la gravedad de los síntomas, la edad de aparición y la evolución. TECNOLOGÍA: Nusinersen (ISIS-SMNRx o ISIS 396443) es un oligonucleótido antisentido actualmente en etapa de investigación clínica para la AME. Es un probable agente modificador de la enfermedad que está diseñado para alterar el empalme de ARN mensajero del gen SMN2 y aumentar la cantidad de proteína SMN funcional producida, compensando así el defecto genético en el gen SMN1, la ausencia de proteína SMN protectora y la consecuente atrofia muscular. OBJETIVO: Evaluar la eficacia y seguridad de Nusinersen en AME tipo 1. COMENTARIOS FINALES: Nusinersen constituye una tecnología sanitaria emergente y experimental para el tratamiento de la AME. La evidencia científica disponible informa eficacia para el tratamiento medido según la escala de HFMSE. El estudio fase 1 publicado incluyó pacientes con AME tipo 2 y 3 pero no tipo 1. Los investigadores consideran que el aumento de 3 a 7 puntos en la escala en el 70% de los pacientes, es clínicamente relevante. El estudio NURTURE obtuvo resultados satisfactorios en pacientes AME tipo 1 en un análisis de datos intermedio, donde demostró un desarrollo motor más compatible con un niño sano. La dosis efectiva de tratamiento hasta ahora es de 9mg intratecal y con un efecto clínico y presencia en el LCR hasta 9 a 14 meses, post aplicación. No se describen eventos adversos de importancia. La información disponible proviene del laboratorio elaborador BIOGEN y IONIS. RECOMENDACIONES: El Nusinersen (SPINRAZANR) constituye un tratamiento experimental, destinado al uso compasivo, exclusivamente a los pocos pacientes con AME tipo 1, 2 ó 3. Debe controlarse su efectividad durante el tratamiento y la aparición de efectos adversos inmediatos y de largo plazo, antes de decidir una nueva aplicación. No se encontró ningún agente terapéutico aprobado en las agencias más importantes, para el tratamiento de esta enfermedad.(AU)