Successful treatment with tocilizumab in a case of Cogan’s syndrome complicated with aortitis

A 69-year-old man with sensorineural hearing loss and iritis was diagnosed with atypical Cogan’s syndrome. He had several systematic manifestations: aortitis, meningitis, panniculitis and seronegative arthritis. Remission induced by treatment with high doses of prednisolone was followed by relapse within 1 year. Although his condition was resistant to various immunosuppressive drugs, including methotrexate, cyclosporine, azathioprine and adalimumab, his symptoms, inflammatory response and quality of life measures were successfully improved by tocilizumab, a humanized anti-interleukin-6 receptor antibody.     

A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations

Background

Retinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas.

Clinical outcomes after posterior cervical decompression and fusion surgery for destructive spondyloarthropathy in patients undergoing long-term hemodialysis: A matched case–control study

BackgroundCervical destructive spondyloarthropathy (DSA) often leads to cervical myelopathy in long-term hemodialysis patients. However, the surgical outcomes after instrumented fusion surgery for cervical DSA are still unclear. The objective of this study was to investigate the clinical outcomes of cervical DSA in comparison with a control group.Materials and methodsA consecutive series of 20 undergoing long-term hemodialysis patients who underwent instrumented fusion surgery for cervical DSA between 2010 and 2016 were included in this study (DSA group). The mean age at surgery was 65 years, and there were 11 men and 9 women. The average length of hemodialysis was 23 years. The age- and sex-matched control group consisted of 20 patients (degenerative conditions). The Japanese Orthopedic Association (JOA) score, recovery rate, complications, and loss of correction of fused level were compared between the groups.ResultsTwo of the 20 patients died due to perioperative complications. More than 1 year of follow-up data after surgery was available for 18 patients. The mean JOA score significantly increased from 5.4 before surgery to 9.7 at 1 year after surgery and 8.3 at the final follow-up (mean: 33.2 ± 21.3 months, P = 0.019). There were no significant differences in the mean recovery rate (41% vs. 37%, P = 0.44) between the DSA group and control group. Loss of correction of more than 5°was significantly higher in the DSA group (44% vs. 10%, P = 0.027). The rate of pseudarthrosis (17% vs. 5%, P = 0.328) and adjacent segment disease (22% vs. 10%, P = 0.17) tended to be higher in the DSA group.DiscussionThe clinical outcomes showed significant recovery in both groups. Therefore, posterior cervical decompression and fusion surgery was effective for treating cervical DSA.     

Discovery of Selective Transforming Growth Factor β Type II Receptor Inhibitors as Antifibrosis Agents

Historically, modulation of transforming growth factor β (TGF-β) signaling has been deemed a rational strategy to treat many disorders, though few successful examples have been reported to date. This difficulty could be partially attributed to the challenges of achieving good specificity over many closely related enzymes that are implicated in distinct phenotypes in organ development and in tissue homeostasis. Recently, fresolimumab and disitertide, two peptidic TGF-β blockers, demonstrated significant therapeutic effects toward human skin fibrosis. Therefore, the selective blockage of TGF-β signaling assures a viable treatment option for fibrotic skin disorders such as systemic sclerosis (SSc). In this report, we disclose selective TGF-β type II receptor (TGF-βRII) inhibitors that exhibited high functional selectivity in cell-based assays. The representative compound 29 attenuated collagen type I alpha 1 chain (COL1A1) expression in a mouse fibrosis model, which suggests that selective inhibition of TGF-βRII-dependent signaling could be a new treatment for fibrotic disorders.     

The position of the vertebral artery V1 segment relative to the C7 vertebra

BackgroundThe vertebral artery (VA) usually enters the transverse foramen at the C6 level. Thus, surgeons prefer to insert pedicle screws (PSs) at C7, but this does not eliminate the risk of VA injury. We aimed to clarify anatomical features of the VA V1 segment at the C7 pedicle level, based on computed tomographic angiography (CTA) of 81 consecutive patients.MethodsWe examined the course of the VA V1 segment on axial CTA images. VA position was classified according to its alignment with the anterior (A), middle (M), or posterior (P) third of the C7 vertebral body at the pedicle level. We also assessed the prevalence of hypoplastic VA (HVA). We measured the distance (VED) from the optimum C7 PS entry point (Ep) to the center of the VA. We also measured the angles formed by the vertebral midline and a line from the inner edge of the VA to the Ep (the VEA), and by the vertebral midline and a line from the inner edge of the pedicle to the Ep (the PEA).ResultsThe variant location of the VA to the C7 vertebra was A in 13 courses (8.1%), M in 123 (76.9%), and P in 20 (12.5%). HVA was present in the contralateral side in 7 of 20 courses (35%) in the P group, and in 8 of 127 courses (6.3%) in the M group (p < 0.05). The mean VED was 20.2 mm, the mean VEA 6.9°, and the mean PEA angle was 36.3°.ConclusionThe 20 VA courses in the P group (12.5% of the total VA courses) were relatively close to the C7 Ep. HVA was present contralateral to the VA in 7 of 20 courses in the P group. CTA should be considered before proceeding with, even if, C7 PS instrumentation, to avoid unexpected pitfall.     

Promoter methylation of leukemia inhibitory factor receptor gene in colorectal carcinoma

Aberrant methylation of gene promoters and corresponding loss of gene expression plays a critical role in the initiation and progression of colorectal cancer. An IL-6-type cytokine receptor, leukemia inhibitory factor receptor (LIFR), is a component of cell-surface receptor complexes for multifunctional cytokines such as LIF. Herein, we report that LIFR is methylated in human colon cancer. LIFR promoter was methylated in primary tumor tissues with high frequency (65%, 52/80). Quantitative methylation-specific PCR (TaqMan-MSP) demonstrated differential promoter methylation of LIFR in primary colorectal cancer tissues as compared to normal colon tissues (5%, 4/80). LIFR methylation was not detectable in 13 normal colon mucosa samples obtained from patients without cancer. The mRNA expression of LIFR was significantly down-regulated in colon cancer tissues as compared to corresponding normal tissues. A strong expression of LIFR protein was observed in all non-malignant normal and adjacent normal colon mucosa tissues whereas down-regulated LIFR protein expression was observed in primary tumors. These results demonstrate that cancer-specific methylation and a specific decrease of LIFR expression are a common inactivation event in colon cancer development.