Targeting Inflammation and Oxidative Stress to Improve Outcomes in a TNBS Murine Crohn's Colitis Model.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn's disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn's disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn's colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.

In utero Diagnosis of Spinal Dermal Sinus.

INTRODUCTION: Congenital dermal sinus (CDS) is an open neural tube defect (NTD) that occurs in 1 in 2,500 births a year and often goes undetected until patients present with complications like infection and neurological deficits. Early diagnosis and repair of CDS may prevent formation of these complications. In utero diagnosis of these lesions may improve long-term outcomes by enabling referral to specialty services and planned postnatal repair; however, only 2 such cases have been reported in the literature. We present a third case of in utero diagnosis of CDS with a description and discussion of findings from surgical exploration and pathology. CASE PRESENTATION: Routine prenatal ultrasound scan detected a tethered cystic structure arising from the back of the fetus at 20 weeks of gestation. Dedicated fetal ultrasound confirmed the presence of a cystic lesion protruding through a lamina defect, while fetal magnetic resonance imaging showed an intact spinal cord and meninges, suggesting a diagnosis of CDS. Neurosurgery followed along closely and took the child for surgical exploration on day 2 of life. A fibrous stalk with an intradural component and associated cord tethering was excised. Histology showed fibrous tissue without an epithelial-lined lumen. CONCLUSION: CDS is a form of NTD that occurs from nondisjunction of the cutaneous ectoderm and neuroectoderm during formation of the neural tube. Slight differences in how this error occurs can explain variations seen in this spectrum of disease, including CDS without an epithelial-lined lumen as seen in this case. Newborns with CDS can go undiagnosed for years and present with long-term complications. Fetal imaging can assist in early recognition and surgical excision of CDS in newborns.

Reliability of the classification of cartilage and labral injuries during hip arthroscopy.

To determine interobserver and intraobserver reliabilities of the combination of classification systems, including the Beck and acetabular labral articular disruption (ALAD) systems for transition zone cartilage, the Outerbridge system for acetabular and femoral head cartilage, and the Beck system for labral tears. Additionally, we sought to determine interobserver and intraobserver agreements in the location of injury to labrum and cartilage. Three fellowship trained surgeons reviewed 30 standardized videos of the central compartment with one surgeon re-evaluating the videos. Labral pathology, transition zone cartilage and acetabular cartilage were classified using the Beck, Beck and ALAD systems, and Outerbridge system, respectively. The location of labral tears and transition zone cartilage injury was assessed using a clock face system, and acetabular cartilage injury using a five-zone system. Intra- and interobserver reliabilities are reported as Gwet's agreement coefficients. Interobserver and intraobserver agreement on the location of acetabular cartilage lesions was highest in superior and anterior zones (0.814-0.914). Outerbridge interobserver and intraobserver agreement was >0.90 in most zones of the acetabular cartilage. Interobserver and intraobserver agreement on location of transition zone lesions was 0.844-0.944. The Beck and ALAD classifications showed similar interobserver and intraobserver agreement for transition zone cartilage injury. The Beck classification of labral tears was 0.745 and 0.562 for interobserver and intraobserver agreements, respectively. The Outerbridge classification had almost perfect interobserver and intraobserver agreement in classifying chondral injury of the true acetabular cartilage and femoral head. The Beck and ALAD classifications both showed moderate to substantial interobserver and intraobserver reliabilities for transition zone cartilage injury. The Beck system for classification of labral tears showed substantial agreement among observers and moderate intraobserver agreement. Interobserver agreement on location of labral tears was highest in the region where most tears occur and became lower at the anterior and posterior extents of this region. The available classification systems can be used for documentation regarding intra-articular pathology. However, continued development of a concise and highly reproducible classification system would improve communication.