Lumbar Bracing for Chronic Low Back Pain: A Randomized Controlled Trial.

PURPOSE: We performed this study to evaluate the effect of back bracing to treat patients with chronic low back pain. METHODS: This was a prospective, unblinded, randomized controlled trial of 61 adults with uncomplicated chronic low back pain (>12 wks) and imaging findings of degenerative spondylosis, to assess the effectiveness of a semirigid back brace. All study participants received back school instruction. The treatment group also received a lumbar orthosis and was instructed to wear it as needed for symptom relief. At baseline, 6 wks, 12 wks, and 6 mos after intervention, we collected: Numerical Rating Scale to measure pain intensity, Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EuroQol 5-Dimension (EQ-5D) to measure patient-reported function and quality of life. RESULTS: An interim analysis at the halfway point in enrollment (61 of 120 planned participants) revealed the Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EQ-5D scores in the treatment group to be worse than in the control group, but no significant group differences in Numerical Rating Scale scores. Outcome differences between groups analyzed over time revealed (effect [P]): Pain Disability Questionnaire = 0.84 (0.04); Patient-Reported Outcome Measurement Information System = 0.78 (0.005); EQ-5D = 0.06 (0.01); and Numerical Rating Scale = 0.02 (0.6). We halted the study because continuation was unlikely to produce significant changes to the results. CONCLUSIONS: In patients with uncomplicated chronic low back pain, a back brace when combined with education and exercise instruction did not provide any pain relief compared with education and exercise instruction alone. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Describe the effect of lumbar back bracing on pain intensity in patients with chronic low back pain; (2) Discuss the effects of lumbar back bracing on pain-related disability, function, and quality of life in patients with chronic low back pain; and (3) Understand the role of lumbar back bracing in the treatment of patients with chronic low back pain. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

ß-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma.

Hepatocellular carcinoma (HCC) was thought historically to arise from hepatocytes, but gene expression studies have suggested that it can also arise from fetal progenitor cells or their adult progenitor progeny. Here, we report the identification of a unique population of fetal liver progenitor cells in mice that can serve as a cell of origin in HCC development. In the transgenic model used, mice carry the Cited1-CreER(TM)-GFP BAC transgene in which a tamoxifen-inducible Cre (CreER(TM)) and GFP are controlled by a 190-kb 5' genomic region of Cited1, a transcriptional coactivator protein for CBP/p300. Wnt signaling is critical for regulating self-renewal of progenitor/stem cells and has been implicated in the etiology of cancers of rapidly self-renewing tissues, so we hypothesized that Wnt pathway activation in CreER(TM)-GFP(+) progenitors would result in HCC. In livers from the mouse model, transgene-expressing cells represented 4% of liver cells at E11.5 when other markers were expressed, characteristic of the hepatic stem/progenitor cells that give rise to adult hepatocytes, cholangiocytes, and SOX9(+) periductal cells. By 26 weeks of age, more than 90% of Cited1-CreER(TM)-GFP;Ctnnb1(ex3(fl)) mice with Wnt pathway activation developed HCC and, in some cases, hepatoblastomas and lung metastases. HCC and hepatoblastomas resembled their human counterparts histologically, showing activation of Wnt, Ras/Raf/MAPK, and PI3K/AKT/mTOR pathways and expressing relevant stem/progenitor cell markers. Our results show that Wnt pathway activation is sufficient for malignant transformation of these unique liver progenitor cells, offering functional support for a fetal/adult progenitor origin of some human HCC. We believe this model may offer a valuable new tool to improve understanding of the cellular etiology and biology of HCC and hepatoblastomas and the development of improved therapeutics for these diseases.