Synthesis and characterization of an orally bioavailable small molecule agonist of the apelin receptor.

The apelin receptor (APJ) is a target for cardiovascular indications. Previously, we had identified a novel pyrazole-based agonist 1 ((S)-N-(1-(cyclobutylamino)-1-oxo-5-(piperidin-1-yl)pentan-3-yl)-1-cyclopentyl-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carboxamide hydrochloride) of this GPCR. Systematic modification of 1 was performed to produce compounds with improved potency and ADME properties. Orally bioavailable compound 47 with favorable agonist potency (Ca2+EC50 = 24 nM, cAMPi EC50 = 6.5 nM) and pharmacokinetic properties (clearance ∼20 mL/min/kg in rats) was identified. This compound has vastly reduced brain penetration and is devoid of significant off-target liability. In summary, a potent and selective APJ agonist suitable for in vivo studies of APJ in peripheral tissues after oral administration has been identified.

Cerebellar hemorrhage as a complication of spine surgery.

BACKGROUND: The association between remote cerebellar hematoma (RCH) and spinal surgery is poorly understood and rarely reported. We present seven cases of RCH after spinal surgery. METHODS: Seven patients were diagnosed with RCH utilizing computed tomography and/or magnetic resonance, between 2012 and 2016. Their clinical presentations, imaging data, treatment modalities, and outcome were analyzed. There were five females and two males with an average age of 55.8 ± 8.4 years. The age of onset ranged from 43 to 67 years and the time to clinical presentation ranged from 3 h to 5 days. Patients presented with: diplopia/strabismus (one patient), dysphagia/urinary incontinence (one patient), respiratory arrest (one patient), meningismus (one patient), and dysarthria (two patients), along with other symptoms/signs. RESULTS: Three patients were successfully managed without surgery, two required external ventricular drainage, and two were treated with posterior fossa decompression plus ventriculostomy. Four patients recovered completely, two showed mild residual deficits at discharge, while one expired 7 days postoperatively. CONCLUSION: RCH is an uncommon and underdiagnosed complication of spine surgery. It should be suspected when intracranial symptoms occur after spinal procedures.

Postoperative Supine Position Increases the Risk of Infection After Spinal Surgery by Posterior Approach.

BACKGROUND: Spine surgeries performed via the posterior approach have a higher infection rate. Several theories have been proposed, including poor hygienic condition of bed sheets and traumatized muscle associated with supine position promoting circulatory impairment. We investigated the influence of supine position on the rate of deep wound infection after spine surgery by the posterior approach. METHODS: A total of 106 patients were randomly divided into 2 groups: lateral decubitus only versus dorsal and lateral decubitus. Patient follow-up after hospital discharge was performed at 30, 60, 180, and 360 days. Deep wound infection was diagnosed according to U.S. Centers for Disease Control and Prevention criteria. RESULTS: Patient sample was mainly composed of patients with neoplastic disease and patients with trauma. Postoperative wound infection developed in 12 cases (11.3%), and Streptococcus aureus was the most common pathogen. Incidence of postsurgical deep wound infection was significantly greater in the control group (P = 0.004). CONCLUSIONS: Supine position was significantly correlated with higher rates of wound infection among patients who underwent spine surgery by the posterior approach. Avoidance of supine position may represent a modifiable risk factor to diminish postoperative spine infection rates.

Atypical spinal epidural capillary hemangioma: Case report.

BACKGROUND: Hemangiomas are benign vascular malformations that can involve the spine. Pure epidural hemangiomas are rare and represent only 4% of all epidural lesions. Most hemangiomas are of the cavernous type; the capillary variant is atypical, and only ten cases have been reported in the literature. CASE DESCRIPTION: A 69-year-old female presented with nonspecific dorsal pain. Magnetic resonance imaging (MRI) showed a spinal epidural tumor at the T9-T10 level. Following a T9-T11 laminectomy, the lesion was completely resected en bloc. Histopathologic analysis showed a pure epidural capillary hemangioma with adipose tissue mesenchyma. CONCLUSIONS: Although epidural capillary hemangiomas are extremely rare, they should be considered among the differential diagnoses of extradural, extramedullary spinal lesions. Further, they must be differentiated from other more common lesions such as meningiomas and schwannomas. The recommended surgical management is en bloc gross total excision.

Cervicothoracic Lordosis Can Influence Outcome After Posterior Cervical Spine Surgery.

BACKGROUND: Previous studies on the correlation between cervical sagittal balance with improvement in quality of life showed significant results only for parameters of the anterior translation of the cervical spine (such as C2-C7 SVA). OBJECTIVE: We test whether a new parameter, cervicothoracic lordosis, can predict clinical success in this type of surgery. METHODS: The focused group involved patients who underwent surgical treatment of cervical degenerative disk disease by the posterior approach, due to myelopathy, radiculopathy or a combination of both. Neurologic deficit was measured before and after surgery with the Nurick Scale, postoperative quality of life, physical and mental components of SF-36 and NDI. Cervicothoracic lordosis and various sagittal balance parameters were also measured. Cervicothoracic lordosis was defined as the angle between: a) the line between the centroid of C2 and the centroid of C7; b) the line between the centroid of C7 and the centroid of T6. Correlations between postoperative quality of life and sagittal parameters were calculated. RESULTS: Twenty-nine patients between 27 and 78 years old were evaluated. Surgery types were simple decompression (laminectomy or laminoforaminotomy) (3 patients), laminoplasty (4 patients) and laminectomy with fusion in 22 patients. Significant correlations were found for C2-C7 SVA and cervicothoracic lordosis. C2-C7 SVA correlated negatively with MCS (r=-0.445, p=0.026) and PCS (r=-0.405, p=0.045). Cervicothoracic lordosis correlated positively with MCS (r=0.554, p= 0.004) and PCS (r=0.462, p=0.020) and negatively with NDI (r=-0.416, p=0.031). CONCLUSION: The parameter cervicothoracic lordosis correlates with improvement of quality life after surgery for cervical degenerative disk disease by the posterior approach.

Compressive Myelopathy Due to Ossification of the Ligamentum Flavum: Case Report and Review of the Literature

Ossification of the ligamentum flavum (OLF) is a rare condition in which the ligamentum flavum, due to mechanical, biological and genetic factors, becomes ossified. Due to its nature and anatomic location, OLF produces symptoms characteristic of spinal cord compression. The diagnostic confirmation is based primarily on imaging tests such as computed tomography (CT) and magnetic resonance imaging (MRI). Ossification of the ligamentum flavum most often affects Asian populations, rarely occurring in black people. The authors report a case of a 61-year-old black man with progressive paraparesis due to OLF, and review the literature regarding the pathology's prevalence, pathogenesis, clinical features, diagnosis, treatment and prognosis.

A ossificação do ligamento flavo (OLF) é uma doença rara na qual o ligamento flavo se torna ossificado devido a fatores mecânicos, biológicos e genéticos. Devido à sua natureza e localização anatômica, a OLF produz sintomas característicos de compressão da medula espinhal. A confirmação diagnóstica baseia-se principalmente em exames de imagem, como tomografia computadorizada (TC) e ressonância magnética (RM). A OLF afeta mais comumente populações asiáticas, raramente sendo observada em pacientes negros. Os autores relatam o caso de um homem negro de 61 anos com paraparesia progressiva decorrente de OLF com uma revisão da literatura a respeito da prevalência, patogênese, aspectos clínicos, diagnóstico, tratamento e prognóstico desta patologia.

A simple scoring system for predicting early major complications in spine surgery: the cumulative effect of age and size of surgery.

OBJECTIVE: To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. METHODS: Retrospective analysis of 583 surgically-treated patients. Early "major" complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. RESULTS: Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. CONCLUSIONS: This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.

A simple scoring system for predicting early major complications in spine surgery: the cumulative effect of age and size of surgery / Escore simples para predizer complicações precoces graves em cirurgia de coluna: o efeito cumulativo da idade e tamanho da cirurgia

ABSTRACT Objective To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. Methods Retrospective analysis of 583 surgically-treated patients. Early “major” complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. Results Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. Conclusions This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.

RESUMO Objetivo Analisar os efeitos cumulativos dos fatores de risco associados com complicações precoces graves relacionadas à cirurgia da coluna. Métodos Análise retrospectiva de 583 pacientes tratados cirurgicamente. Complicações graves foram definidas como as que pudessem levar a danos permanentes ou que necessitassem de reinterveção. Um escore foi construído usando modelo de regressão logística. Resultados Noventa e duas complicações precoces graves ocorreram em 76 pacientes (13%). Idade > 60 anos e cirurgia > 3 níveis foram identificadas como fatores de risco independentes na análise multivariada. O escore foi definido como: 0 pontos (nenhum fator de risco), 2 pontos (1 fator) ou 4 pontos (2 fatores). A incidência de complicação grave precoce em cada categoria foi 7% (0 pontos), 15% (2 pontos) e 29% (4 pontos). Conclusões Esse escore balanceado baseado em 2 fatores de risco representa uma ferramenta útil na indicação cirúrgica e para o aconselhamento dos pacientes antes da cirurgia.

Symptomatic thoracic spinal cord compression caused by postsurgical pseudomeningocele.

We report the first case of symptomatic thoracic spinal cord compression caused by postsurgical pseudomeningocele. A 49-year-old man sought treatment for progressive loss of strength in the lower extremities ten months after full neurological recovery for a thoracic (T11) intradural-extramedullary schwannoma. Magnetic resonance imaging revealed a postsurgical thoracic (T11-T12) pseudomeningocele. The surgical approach showed an inadequate dural closure with spontaneous cerebrospinal fluid fistula. The defect was sealed with suture, muscle and biological glue covering. The patient had a good recovery. Pseudomeningocele must take part of the differential diagnosis of myelopathy after thoracic spine surgery.

Symptomatic thoracic spinal cord compression caused by postsurgical pseudomeningocele

We report the first case of symptomatic thoracic spinal cord compression caused by postsurgical pseudomeningocele. A 49-year-old man sought treatment for progressive loss of strength in the lower extremities ten months after full neurological recovery for a thoracic (T11) intradural-extramedullary schwannoma. Magnetic resonance imaging revealed a postsurgical thoracic (T11-T12) pseudomeningocele. The surgical approach showed an inadequate dural closure with spontaneous cerebrospinal fluid fistula. The defect was sealed with suture, muscle and biological glue covering. The patient had a good recovery. Pseudomeningocele must take part of the differential diagnosis of myelopathy after thoracic spine surgery.

Relatamos o primeiro caso de compressão medular torácica sintomática causada por pseudomeningocele pós-operatória. Paciente masculino, 49 anos, apresentou perda progressiva de força nas extremidades inferiores dez meses após recuperação neurológica completa de cirurgia para remoção de schwannoma intradural-extramedular torácico. A ressonância magnética dorsal revelou pseudomeningocele (T11-T12). A abordagem cirúrgica mostrou fechamento dural inadequado com fistula liquórica espontânea. O defeito foi corrigido com sutura, músculo e cola biológica. O paciente teve boa evolução pós-operatória. Pseudomeningocele deve fazer parte do diagnóstico diferencial de mielopatia surgida após cirurgia na coluna dorsal.

Subsidence of thoracolumbar fractures after ro long/fuse short technique

Objetivo: uma das alternativas para o tratamento cirúrgico das fraturas tóra-lombares em explosão(TLBF) é a técnica de instrumentação longa e fusão curta(RLFS) utilizando o sistema de Harrington. A altura do corpo vertebral fraturado geralmente retorna a valores próximos do normal imediatamente após a cirurgia, mas, alguns meses depois, esse ganho é perdido(achatamento). Nosso objetivo é verificar os resultados clínicos e radiológicos com a técnica RLFS com sistema de instrumentação universal. Método: doze casos de TLBF (masculino/feminino=9/3, média de idade=35,7 anos, Escala de Frankel: E=9, C=3) foram estudados. Através de abordagem posterior, instrumentação universal foi realizada dois níveis acima e dois níveis abaixo da vértebra fraturada. Enxerto ósseo foi coclocado de um nível acima a um nível abaixo da fratura. Após pelo menos nove meses, o instrumental localizado além da área enxertada foi removido. Os resultados clínicos foram medidos pela Escala de Frankel e pelo formulário SF-36. Resultado: não se observou piora neurológica. Todos os pacientes com lesão neurológica, exceto um deles, melhoraram um grau na escala de Frankel. Os parãmetros radiográficos melhoraram após a primeira cirurgia, mas o ganho reduziu após a remoção do material. A cifose pós-operatória interferiu negativamente na qualidade de vida dos pacientes.

Um método para medida de movimento em estudos biomecânicos de coluna vertebral / Method to measure movement in biomechanical studies of the spine

É apresentado um método que permite a medida de movimentos rotacionais executados por um segmento de movimento espinal em torno dos três eixos ortogonais durante estudos biomecânicos. A medida é obtida através do registro da posição de um ponteiro acoplado ao segmento de movimento, o qual desliza sobre uma superf¡cie de papel milimetrado. O método é simples e tem baixo custo.

Fratura do cinto de segurança da coluna lombar / Seatbelt fractures of the lumbar spine

Seis pacientes com fraturas do cinto de segurança da coluna lombar foram tratados com reduçäo, fixaçao interna com instrumental de Harrington de compressäo e artrodese seguida de imobilizaçäo externa. Em todos os pacientes foi obtida reduçäo satisfatória e artrodese sólida. Nenhuma complicaçäo relacionada ao método foi encontrada.