The salient role of microRNAs in atherogenesis.

Atherosclerosis, a chronic inflammatory condition that is characterized by the accumulation of lipid-loaded macrophages, occurs preferentially at the arterial branching points where disturbed flow is prominent. The pathogenesis of atherosclerotic lesion formation is a multistage process involving multiple cell types, inflammatory mediators and hemodynamic forces in the vessel wall in response to atherogenic stimuli. Researches from the past decade have uncovered the critical roles of microRNAs (miRNAs) in regulating multiple pathophysiological effects and signaling pathways in endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages and lipid homeostasis, which are key in atherosclerotic lesion formation. The expression of these miRNAs are either in response to biomechanical (flow-responsive) or biochemical (non-flow-responsive) stimuli. Recent evidences also indicate an important role for long non-coding RNAs (lncRNAs) in mediating several atherosclerotic processes. In this review, we provide a detailed summary on the current paradigms in miRNA-dependent regulation, the emerging role of lncRNAs in the initiation and progression of atherosclerosis, and clinical interventions targeting these in an attempt to develop novel diagnostics and treatments for atherosclerosis.

Difficulties in Treating Postirradiation Kyphosis in Adults: A Series of Five Cases.

STUDY DESIGN: Clinical case series. OBJECTIVE: To assess objective outcomes of surgical correction of post-external beam radiation therapy (ERBT) kyphosis in a series of five adults. SUMMARY OF BACKGROUND DATA: EBRT is a well-established treatment for many cancers in children and adults. One complication associated with EBRT is postirradiation spine deformity. Scoliosis is the most common deformity, but kyphosis also occurs frequently. Differences in deformity patterns are likely related to the location and intensity of radiation. To our knowledge, no studies have addressed treatment of these deformities in adults, and the most recent case series (of children) was published in 2005. METHODS: We present a series of five adults who underwent surgery for postirradiation kyphosis, with a mean follow-up of 3.8 years (range, 2.5-6.2 years). RESULTS: Surgery improved the kyphotic deformity in all patients. Overall mean kyphotic deformity correction was 56° and was larger for cervical/cervicothoracic deformities (mean, 76°) than for lumbar deformities (mean, 42°) at midterm follow-up. Patients reported significant improvements in pain and self-image. Consistent with prior case series of children, we observed a high rate of complications (mean, 1.4 complications per patient) in adults. Three patients each underwent an unplanned surgical procedure because of a complication. CONCLUSION: The surgical treatment of postirradiation kyphotic spinal deformity is challenging, with common postoperative complications such as infection, instrumentation failure, and pseudarthrosis. However, with modern surgical techniques and spinal instrumentation, excellent deformity correction can be achieved and maintained. We recommend performing a two-stage procedure for cervicothoracic deformity, with anterior release followed by posterior fusion and instrumentation. In thoracolumbar deformities, correction can be achieved through single-stage posterior fusion. Rigid spinopelvic fixation with sacral-alar-iliac screws and second-stage anterior lumbar interbody fusion at L5-S1 is recommended to reduce nonunion risk. Cement augmentation of proximal and distal anchors can help prevent junctional failure. LEVEL OF EVIDENCE: Level IV.

"As Black as Ink": A Case of Alkaptonuria-Associated Myelopathy and a Review of the Literature.

STUDY DESIGN: Case report and literature review. OBJECTIVE: To characterize the rare presentation of myelopathy occurring secondary to alkaptonuria and to evaluate the available evidence regarding its treatment. SUMMARY OF BACKGROUND DATA: Alkaptonuria is an autosomal recessive genetic condition with an estimated incidence of 1 in 250,000 to 1 in 1,000,000 people. Mutation of the enzyme homogentisate 1,2-dioxygenase leads to the production of high levels of homogentisic acid, with subsequent deposition in ligaments, cartilage, and menisci. Involvement of the spine is termed "ochronotic spondyloarthropathy," of which myelopathy is an uncommon presentation. METHODS: We present the case of a 57-year-old man with alkaptonuria-associated myelopathy, who underwent surgical decompression. Ten additional cases were identified in the literature by a systematic search of PubMed and Google Scholar. RESULTS: In a patient presenting with myelopathy, alkaptonuria may be suspected because of medical history, family history, symptoms (including darkened urine, pigmented ear cartilage, and sclera), or radiographic changes, such as multilevel disc collapse, progressive wafer-like disc calcification, extensive osteophyte formation, and spinal deformity. The diagnosis can be confirmed by urine homogentisic acid testing. Of the 11 patients presented here or identified in the literature, 2 were treated nonoperatively, 8 were treated with decompressive spinal surgery, and treatment of the myelopathy was not discussed for 1 patient. In all cases in which outcomes were reported, substantial improvement in the patient's condition was seen. CONCLUSION: Alkaptonuria is a rare cause of myelopathy, but one that clinicians should understand. Although no disease-modifying treatment currently exists for alkaptonuria, the use of symptomatic treatments and, particularly, surgical decompression is recommended to address myelopathy if it develops. LEVEL OF EVIDENCE: 4.

Trends in isolated lumbar spinal stenosis surgery among working US adults aged 40-64 years, 2010-2014.

OBJECTIVE Recommendations for the surgical treatment of isolated lumbar spinal stenosis (LSS) (i.e., in the absence of concomitant scoliosis or spondylolisthesis) are unclear. The aims of this study were to investigate trends in the surgical treatment of isolated LSS in US adults and determine implications for outcomes. METHODS The authors analyzed inpatient and outpatient claims from the Truven Health Analytics MarketScan Commercial Claims and Encounters Database for 20,279 patients aged 40-64 years who underwent surgery for LSS between 2010 and 2014. Only patients with continuous 12-month insurance coverage after surgery were included. The rates of decompression with arthrodesis versus decompression only and of simple (1- or 2-level, single-approach) versus complex (> 2-level or combined-approach) arthrodesis were analyzed by year and geographic region. These trends were further analyzed with respect to complications, length of hospital stay, payments made to the hospital, and patient discharge status. Statistical significance was set at p < 0.05. RESULTS The proportion of patients who underwent decompression with arthrodesis compared with decompression only increased significantly and linearly from 2010 to 2014 (OR 1.08; 95% CI 1.06-1.10). Arthrodesis was more likely to be complex rather than simple with each subsequent year (OR 1.4; 95% CI 1.33-1.49). This trend was accompanied by an increased likelihood of postoperative complications (OR 1.11; 95% CI 1.02-1.21), higher costs (payments increased by a mean of US$1633 per year; 95% CI 1327-1939), and greater likelihood of being discharged to a skilled nursing facility as opposed to home (OR 1.11; 95% CI 1.03-1.20). The South and Midwest regions of the US had the highest proportions of patients undergoing arthrodesis (48% and 42%, respectively). The mean length of hospital stay did not change significantly (p = 0.324). CONCLUSIONS From 2010 to 2014, the proportion of adults undergoing decompression with arthrodesis versus decompression only for the treatment of LSS increased, especially in the South and Midwest regions of the US. A greater proportion of these fusions were complex and were associated with more complications, higher costs, and a greater likelihood of being discharged to a skilled nursing facility.