Upper Lumbar Pedicle Screw Insertion Using Three-Dimensional Fluoroscopy Navigation:Assessment of Clinical Accuracy

We used a navigation system to insert 128 pedicle screws into 69 vertebrae (L1 to L3) of 49 consecutive patients. We assessed the pedicle isthmic width and the permission angle for pedicle screw insertion. The permission angle is the angle defined by the greatest medial and lateral trajectories allowable when placing the screw through the center of the pedicle. The rate of narrow-width pedicles (isthmic width less than 5mm) was 5 of 60 pedicles (8%) at L1, 4 of 60 pedicles (7%) at L2, and none (0%) at L3, L4 and L5. The rate of narrow-angle pedicles (a permission angle less than 15 degrees) was 21 of 60 pedicles (35%) at L1, 7 of 60 (12%) at L2, 3 of 60 (5%) at L3, and none (0%) at L4 and L5. Of 128 pedicle screws inserted into 69 vertebrae from L1 to L3, 125 (97.7%) were classified as Grade 1 (no pedicle perforation). In general, the upper lumbar vertebrae have more narrow-width and -angle pedicles. However, we could reduce the rate of pedicle screw misplacement in upper lumbar vertebra using a three-dimensional fluoroscopy and navigation system

Clinical Accuracy of Three-Dimensional Fluoroscopy (IsoC-3D)-Assisted Upper Thoracic Pedicle Screw Insertion

Correct screw placement is especially difficult in the upper thoracic vertebrae. At the cervicothoracic junction (C7-T2), problems can arise because of the narrowness of the pedicle and the difficulty of using a lateral image intensifier there. Other upper thoracic vertebrae (T3-6) pose a problem for screw insertion also because of the narrower pedicle. We inserted 154 pedicle screws into 78 vertebrae (C7 to T6) in 38 patients. Screws were placed using intraoperative data acquisition by an isocentric C-arm fluoroscope (Siremobile Iso-C3D) and computer navigation. Out of 90 pedicle screws inserted into 45 vertebrae between C7 and T2, 87 of the 90 (96.7%) screws were classified as grade 1 (no perforation). Of 64 pedicle screws inserted into 33 vertebrae between T3 and T6, 61 of 64 (95.3%) screws were classified as grade 1. In this study, we reduced pedicle screw misplacement at the level of the C7 and upper thoracic (T1-6) vertebrae using the three-dimensional fluoroscopy navigation system

Recovery of Motor Function in Patients with Subaxial Cervical Spine Injury Relevant to the Fracture Pattern

In this study, we studied the relationship between fracture patterns and motor function recovery in 70 consecutive patients with cervical spinal cord injury. Fractures were categorized into 6 fracture types and subdivided into stages according to the Allen-Ferguson classification system:compressive flexion (CF), distractive flexion (DF), compressive extension (CE), distractive extension (DE), vertical compression (VC) and lateral flexion (LF). Paralysis was evaluated using the American Spinal Injury Association (ASIA) impairment scale at the time of injury and 3 months afterwards. The residual rate of complete motor palsy (ASIA grade A or B) at the final examination was higher in those patients with DE fractures than those with CF, DF or CE. The final outcomes were as follows. Of the 14 patients who were classified with CF fractures, residual palsy was frequently seen in patients who had stage 5 injury. Of the 27 patients with DF fractures, residual palsy occurred in about half of the patients who had stage 4 or 5 injury. Of the 18 patients with CE fractures, residual palsy occurred in half of the patients with stage 3 injury or higher. Finally, of the 7 patients with DE fractures, the rate of residual palsy was high even for the stage 1 and 2 cases;indeed, all DE patients who had complete motor palsy at the first examination had residual palsy at the final examination. Accordingly, we conclude that motor recovery may be related to fracture pattern

A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways

Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) play key roles in progression of renal fibrosis, dual blockade of TGF-β1 and TNF-α is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-α activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-α effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-α activity was mediated by inhibiting IκB kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice. Additionally, MA-35 concurrently showed an anti-TGF-β1 effect by inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-β1-induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney, which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis with the downregulation of inflammatory cytokines and fibrotic gene expressions. Furthermore, MA-35 inhibited TGF-β1-induced H3K4me1 histone modification of the fibrotic gene promoter, leading to a decrease in the fibrotic gene expression. MA-35 affects multiple signaling pathways involved in the fibrosis and may recover epigenetic modification; therefore, it could possibly be a novel therapeutic drug for fibrosis

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial

RTCB Complex Regulates Stress-Induced tRNA Cleavage

Under stress conditions, transfer RNAs (tRNAs) are cleaved by stress-responsive RNases such as angiogenin, generating tRNA-derived RNAs called tiRNAs. As tiRNAs contribute to cytoprotection through inhibition of translation and prevention of apoptosis, the regulation of tiRNA production is critical for cellular stress response. Here, we show that RTCB ligase complex (RTCB-LC), an RNA ligase complex involved in endoplasmic reticulum (ER) stress response and precursor tRNA splicing, negatively regulates stress-induced tiRNA production. Knockdown of RTCB significantly increased stress-induced tiRNA production, suggesting that RTCB-LC negatively regulates tiRNA production. Gel-purified tiRNAs were repaired to full-length tRNAs by RtcB in vitro, suggesting that RTCB-LC can generate full length tRNAs from tiRNAs. As RTCB-LC is inhibited under oxidative stress, we further investigated whether tiRNA production is promoted through the inhibition of RTCB-LC under oxidative stress. Although hydrogen peroxide (H2O2) itself did not induce tiRNA production, it rapidly boosted tiRNA production under the condition where stress-responsive RNases are activated. We propose a model of stress-induced tiRNA production consisting of two factors, a trigger and booster. This RTCB-LC-mediated boosting mechanism may contribute to the effective stress response in the cell