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Study Design: A retrospective cohort analysis. Objective: To determine the effect of biological agents (BAs) on the development and progression of cervical spine lesions and identify predictors of lesion progression. Summary Of Background Data: The introduction of BAs has facilitated advances in the treatment of rheumatoid arthritis (RA). BAs reduce disease activity and limit structural joint damage. However, the effect of BAs on cervical spine lesions remains unclear. Methods: Thirty-eight subjects who received more than 2 years of continuous BA treatment were enrolled. The mean x-ray interval was 4.4 years. RA activity was evaluated by disease activity score (DAS)-C reactive protein (CRP) and matrix metalloproteinase (MMP)-3. Radiographical definitions of cervical lesions were atlanto-dental interval (ADI) more than 3 mm for atlanto-axial subluxation (AAS), Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or posterior listhesis more than 2 mm for subaxial subluxation (SS). Definitions of radiographical progression were an increase of ADI more than 2 mm for AAS, a decrease of both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an increase of listhesis more than 2 mm for SS. Results: RA activity responded dramatically to BA therapy (DAS-CRP from 4.3 to 2.3, P < 0.01; MMP-3 from 207.9 ng/mL to 105.6 ng/mL, P < 0.01). Baseline radiographical evaluation showed no pre-existing cervical spine lesions in 12 cases, AAS in 15 cases, and VS in 11 cases. Radiological progression was found in 1 (8%) patient in the no lesion group, 12 patients (80%) in the AAS group, and 9 patients (80%) in the VS group. The incidence of progression was significantly lower in the no lesion group compared with the other groups. Multivariate regression analysis showed that the presence of pre-existing cervical lesions was the single greatest predictor of progression. Conclusion: BAs prevented the development of de novo cervical spine lesions in patients with RA, but failed to inhibit progression of pre-existing RA lesions. [ABSTRACT FROM AUTHOR]

Study Design: Prospective study to investigate the incidence of axial pain in the 3 different procedures of laminoplasty. Objective: To inquire which is more important in the development of axial pain after laminoplasty: C7 or deep extensor muscles. Summary Of Background Data: The etiology of axial pain remains largely unknown. Some surgeons have attempted to preserve the paravertebral muscles with innovative procedures of laminoplasty and thereby reduce the incidence of axial pain. Meanwhile, we have reported that axial pain can be prevented by avoiding inclusion of C7 in laminoplasty. Methods: There were 91 patients with myelopathy who underwent our original laminoplasty, in which the deep extensor muscles were completely preserved exclusively on the hinged side. Until 2001, all candidates for laminoplasty underwent this procedure from C3-C7 (left-opened C3-C7 group, n = 37). From 2002, the same procedure was performed from C3-C6 (left-opened C3-C6 group, n = 31). From 2004, the opened side was changed from left to right (right-opened C3-C6 group, n = 23). Axial neck pain was graded as severe, moderate, or mild. Early pain during the first month after surgery and late pain during the first year after surgery were investigated. The laterality of early pain in the C3-C6 groups was recorded. Results: Significant early pain graded severe or moderate was observed in 49% in the left-opened C3-C7 group, but 15% in the left- or right-opened C3-C6 groups (P = 0.0008). Significant late pain was noted in 30% in the left-opened C3-C7 group and in 5.6% in the C3-C6 groups (P = 0.0036). Early axial pain, which usually was mild, was predominantly observed on the opened side in the C3-C6 groups. Conclusion: To prevent axial pain, C7 should not be included in cervical laminoplasty, while detachment of the deep extensor muscles does not result in significant axial pain. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A literature review was conducted to integrate and compile available reports on postoperative C5 palsy. OBJECTIVES: To review the clinical features, possible pathogenesis, and procedures for treatment and prevention of postoperative C5 palsy as a complication of surgery for cervical compression myelopathy. SUMMARY OF BACKGROUND DATA: Although postoperative C5 palsy develops in approximately 5% of patients after decompression surgery of the cervical spine, its pathogenesis and the options for prevention and treatment remain unidentified and many controversies exist. METHOD: We reviewed and analyzed papers published from 1986 to 2002 regarding C5 palsy as a postoperative complication. Statistical comparisons were made when appropriate. RESULTS: Postoperative C5 palsy is reported to occur in an average of 4.6% of patients after surgery for cervical compression myelopathy. No significant differences were noted between patients undergoing anterior decompression and fusion and laminoplasty, nor were distinctions apparent between unilateral hinge laminoplasty and French-door laminoplasty, or between cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Two theories were put forth to account for the pathogenesis of C5 palsy: nerve root injury and segmental spinal cord disorder. Neither of these hypotheses has been consistently supported and evidence to refute each hypothesis can be found in the literature. Recently, surgeons have advocated foraminotomy combined with laminoplasty to prevent or treat C5 palsy, but further studies into the efficacy of this procedure are needed. Although patients with C5 palsy generally have a good prognosis for neurologic and functional recovery, those with severe paralysis require significantly longer recovery times when compared to more mild cases. CONCLUSION: The incidence of postoperative C5 palsy has been reported at 4.6% after surgery for cervical compression myelopathy and this value has not varied with different surgical procedures or disease etiologies. The pathogenesis of postoperative C5 palsy remains unclear at the present time. Patients with postoperative C5 palsy generally have a good prognosis for functional recovery, but the severely paralyzed cases required significantly longer recovery times than the mild cases. [ABSTRACT FROM AUTHOR]

Inotuzumab ozogamicin (IO), a novel therapeutic drug for relapsed or refractory acute lymphoblastic leukemia (RR)‑(ALL), is a humanized anti‑cluster of differentiation (CD) 22 monoclonal antibody conjugated with calicheamicin that causes DNA single‑ and double‑strand breaks. Although the efficacy of IO is significantly improved compared with that of conventional chemotherapies, the prognosis for RR‑ALL remains poor, highlighting the need for more effective treatment strategies. The present study examined the role of DNA damage repair inhibition using the poly (ADP‑ribose) polymerase (PARP) inhibitors olaparib or talazoparib on the enhancement of the antitumor effects of IO on B‑ALL cells in vitro . The Reh, Philadelphia (Ph) ‑ B‑ALL and the SUP‑B15 Ph + B‑ALL cell lines were used for experiments. Both cell lines were ~90% CD22 + . The half‑maximal inhibitory concentration (IC 50 ) values of IO were 5.3 and 49.7 ng/ml for Reh and SUP‑B15 cells, respectively. The IC 50 values of IO combined with minimally toxic concentrations of olaparib or talazoparib were 0.8 and 2.9 ng/ml for Reh cells, respectively, and 36.1 and 39.6 ng/ml for SUP‑B15 cells, respectively. The combination index of IO with olaparib and talazoparib were 0.19 and 0.56 for Reh cells and 0.76 and 0.89 for SUP‑B15 cells, demonstrating synergistic effects in all combinations. Moreover, the addition of minimally toxic concentrations of PARP inhibitors augmented IO‑induced apoptosis. The alkaline comet assay, which quantitates the amount of DNA strand breaks, was used to investigate the degree to which DNA damage observed 1 h after IO administration was repaired 6 h later, reflecting successful repair of DNA strand breaks. However, DNA strand breaks persisted 6 h after IO administration combined with olaparib or talazoparib, suggesting inhibition of the repair processes by PARP inhibitors. Adding olaparib or talazoparib thus synergized the antitumor effects of IO by inhibiting DNA strand break repair via the inhibition of PARP.