Short-segment spinal fusion for chronic low back pain with bone marrow edema adjacent to the vertebral endplate in adult spinal deformity.

PURPOSE: Corrective long spinal fusion is a widely accepted surgical method for patients with adult spinal deformities. However, instrumented long fusion is associated with a significant risk of complications. Therefore, we aimed to assess the success of short-segment spinal fusion, particularly for bone marrow edema (BME) adjacent to the vertebral endplate, in patients with low back pain (LBP) and spinal deformity. METHODS: A prospective study was performed at multiple hospitals wherein we monitored patients with spinal deformities and accompanying LBP. Patients aged ≥ 50 years with a minimum LBP severity score of 40 mm on the visual analog scale (VAS) were included in the study. We also included patients with lumbar BME on magnetic resonance imaging. Short spinal fusion was performed on segments with BME. Clinical evaluations of LBP on VAS and Oswestry Disability Index (ODI), and radiological parameters for sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL) and pelvic tilt (PT) were carried out. RESULTS: Overall, 35 patients (22 men and 13 women), with a mean age of 66.7 years and a mean follow-up period of 32 months, were included in the study. The mean VAS and ODI scores were 72.4 mm and 49.0% before surgery and 25.5 mm and 29.9% at the final follow-up, respectively; these parameters significantly improved after surgery. The SVA, PI-LL, and PT scores were 70.1 mm, 20.9°, and 22.8° before surgery and 85.4 mm, 13.8°, and 22.7° at the final follow-up, respectively. The spinal alignment parameters did not change significantly after surgery. CONCLUSIONS: Short-segment spinal fusion is effective for treating LBP and spinal deformity with BME adjacent to the vertebral endplate without spinal correction.

Development of a novel animal model of lumbar vertebral endplate lesion by intervertebral disk injection of monosodium iodoacetate in rats.

PURPOSE: Vertebral endplate lesions (EPLs) caused by severe disk degeneration are associated with low back pain. However, its pathophysiology remains unclear. In this study, we aimed to develop a vertebral EPL rat model mimicking severe intervertebral disk (IVD) degeneration by injecting monosodium iodoacetate (MIA) into the IVDs and evaluating it by assessing pain-related behavior, micro-computed tomography (CT) findings, and histological changes. METHODS: MIA was injected into the L4-5 and L5-6 IVDs of Sprague-Dawley rats. Their behavior was examined by measuring the total distance traveled and the total number of rearing in an open square arena. Bone alterations and volume around the vertebral endplate were assessed using micro-CT. Safranin-O staining, immunohistochemistry, and tartrate-resistant acid phosphatase (TRAP) staining were performed for histological assessment. RESULTS: The total distance and number of rearing times in the open field were significantly reduced in a time-dependent manner. Micro-CT revealed intervertebral osteophytes and irregularities in the endplates at 12 weeks. The bone volume/tissue volume (BV/TV) around the endplates significantly increased from 6 weeks onward. Safranin-O staining revealed severe degeneration of IVDs and endplate disorders in a dose- and time-dependent manner. Calcitonin gene-related peptide-positive nerve fibers significantly increased from 6 weeks onward. However, the number of osteoclasts decreased over time. CONCLUSION: Our rat EPL model showed progressive morphological vertebral endplate changes in a time- and concentration-dependent manner, similar to the degenerative changes in human IVDs. This model can be used as an animal model of severe IVD degeneration to better understand the pathophysiology of EPL.

Antibody recognition of complement factor H reveals a flexible loop involved in atypical hemolytic uremic syndrome pathogenesis.

Atypical hemolytic uremic syndrome (aHUS) is a disease associated with dysregulation of the immune complement system, especially of the alternative pathway (AP). Complement factor H (CFH), consisting of 20 domains called complement control protein (CCP1-20), downregulates the AP as a cofactor for mediating C3 inactivation by complement factor I. However, anomalies related to CFH are known to cause excessive complement activation and cytotoxicity. In aHUS, mutations and the presence of anti-CFH autoantibodies (AAbs) have been reported as plausible causes of CFH dysfunction, and it is known that CFH-related aHUS carries a high probability of end-stage renal disease. Elucidating the detailed functions of CFH at the molecular level will help to understand aHUS pathogenesis. Herein, we used biophysical data to reveal that a heavy-chain antibody fragment, termed VHH4, recognized CFH with high affinity. Hemolytic assays also indicated that VHH4 disrupted the protective function of CFH on sheep erythrocytes. Furthermore, X-ray crystallography revealed that VHH4 recognized the Leu1181-Leu1189CCP20 loop, a known anti-CFH AAbs epitope. We next analyzed the dynamics of the C-terminal region of CFH and showed that the epitopes recognized by anti-CFH AAbs and VHH4 were the most flexible regions in CCP18-20. Finally, we conducted mutation analyses to elucidate the mechanism of VHH4 recognition of CFH and revealed that VHH4 inserts the Trp1183CCP20 residue of CFH into the pocket formed by the complementary determining region 3 loop. These results suggested that anti-CFH AAbs may adopt a similar molecular mechanism to recognize the flexible loop of Leu1181-Leu1189CCP20, leading to aHUS pathogenesis.

A high-sensitivity ELISA for detection of human FGF18 in culture supernatants from tumor cell lines.

Fibroblast growth factor 18 (FGF18) is elevated in several human cancers, such as gastrointestinal and ovarian cancers, and stimulates the proliferation of tumor cells. This suggests that FGF18 may be a promising candidate biomarker in cancer patients. However, the lack of a high-sensitivity enzyme-linked immunosorbent assay (ELISA) does not permit testing of this possibility. In this study, we generated monoclonal antibodies against human FGF18 and developed a high-sensitivity ELISA to measure human FGF18 at concentrations as low as 10 pg/mL. Of the eight tumor cell lines investigated, we detected human FGF18 in culture supernatants from four tumor cell lines, including HeLa, OVCAR-3, BxPC-3, and SW620 cells, albeit the production levels were relatively low in the latter two cell lines. Moreover, the in-house ELISA could detect murine FGF18 in sera from mice overexpressing murine Fgf18 in hepatocytes, although the sensitivity in detecting murine FGF18 was relatively low. This FGF18 ELISA could be a valuable tool to validate FGF18 as a potential biomarker for cancer patients and to test the contribution of FGF18 for various disease models invivo and in vitro.

Vertebral osteomyelitis due to Mycobacterium abscessus subsp. massiliense with paravertebral abscess: A case report and review.

The incidence of vertebral osteomyelitis (VO) caused by non-tuberculosis mycobacteria (NTM) without immunocompetence is extremely rare. Herein, we reported on a case of VO caused by NTM. A 38-year-old man was admitted to our hospital with persisting low back and leg pain which had lasted for a year. Before coming to our hospital, the patient was treated with antibiotics and iliopsoas muscle drainage. The biopsy confirmed the presence of a NTM, Mycobacterium abscessus subsp. massiliense. Several tests were conducted which showed the infection had progressively increased, such as vertebral endplate destruction on plain radiography, computed tomography scan, and epidural and paraspinal muscle abscesses on magnetic resonance imaging. The patient underwent radical debridement, anterior intervertebral fusion with bone graft, and posterior instrumentation with antibiotic administration. A year later, the patient's low back and leg pain was relieved without any analgetic. VO due to NTM is rare but can be treated with multimodal therapy.

Structural basis for antigen recognition by methylated lysine-specific antibodies.

Proteins are modulated by a variety of posttranslational modifications including methylation. Despite its importance, the majority of protein methylation modifications discovered by mass spectrometric analyses are functionally uncharacterized, partly owing to the difficulty in obtaining reliable methylsite-specific antibodies. To elucidate how functional methylsite-specific antibodies recognize the antigens and lead to the development of a novel method to create such antibodies, we use an immunized library paired with phage display to create rabbit monoclonal antibodies recognizing trimethylated Lys260 of MAP3K2 as a representative substrate. We isolated several methylsite-specific antibodies that contained unique complementarity determining region sequence. We characterized the mode of antigen recognition by each of these antibodies using structural and biophysical analyses, revealing the molecular details, such as binding affinity toward methylated/nonmethylated antigens and structural motif that is responsible for recognition of the methylated lysine residue, by which each antibody recognized the target antigen. In addition, the comparison with the results of Western blotting analysis suggests a critical antigen recognition mode to generate cross-reactivity to protein and peptide antigen of the antibodies. Computational simulations effectively recapitulated our biophysical data, capturing the antibodies of differing affinity and specificity. Our exhaustive characterization provides molecular architectures of functional methylsite-specific antibodies and thus should contribute to the development of a general method to generate functional methylsite-specific antibodies by de novo design.

Development of a rat model with lumbar vertebral endplate lesion.

PURPOSE: Vertebral endplate lesion (EPL) caused by severe disc degeneration is associated with low back pain. However, there is no suitable animal model to elucidate the pathophysiology of EPL. This study aimed to develop a rat model of EPL and evaluate rat behavior and imaging and histological findings. METHODS: The L4-5 intervertebral discs of Sprague-Dawley rats were transperitoneally removed, except for the outer annulus fibrosus and cartilage endplate, in the EPL group. The L4-5 discs were not removed and simply exposed in the sham group. Changes around the vertebral endplate on magnetic resonance imaging (MRI) and computed tomography (CT) were evaluated. Additionally, pain-related behavioral and histological assessments were performed. RESULTS: In the EPL group, a low-signal area around the vertebral endplate was observed on T1-weighted and T2-weighted fat-saturated MRI at 8 weeks or later after surgery. In the same group, CT showed osteosclerosis around the vertebral endplate at 12 weeks after surgery. The sham group did not show abnormal imaging features on the MRI and CT. Behavioral evaluation showed that the EPL group had a significantly longer grooming time than the sham group. Conversely, the 12-week postoperative locomotion time and the 1- and 12-week postoperative standing times were significantly shorter in the EPL group than in the sham group. Histological evaluation showed a high degree of vertebral endplate degeneration and an increased number of osteoclasts and proportion of nerve fibers expressing calcitonin gene-related peptide in the EPL group compared to those in the sham group. CONCLUSION: Our rat EPL model showed pain-related behavioral patterns and an increased expression of pain-related neuropeptide. This model could contribute to the study of the pathophysiology of EPL and will help in the treatment of low back pain in the future.

Comparison of the electrophysiological characteristics of tight filum terminale and tethered cord syndrome.

PURPOSE: This study aims to characterize tight filum terminale (TFT) in motor evoked potential (MEP) testing by comparing TFT patients with both tethered cord syndrome (TCS) patients and healthy subjects. METHODS: Fifty TFT patients, 18 TCS patients, and 35 healthy volunteers participated in this study. We recorded MEPs following transcranial magnetic stimulation from the bilateral abductor hallucis muscles as well as compound muscle action potentials and F-waves evoked by electrical stimulation of the tibial nerve from the bilateral abductor pollicis brevis muscles. The peripheral conduction time (PCT) was calculated from the latency of the compound action potential and F-wave. Furthermore, the central motor conduction time (CMCT) was calculated by subtracting PCT from MEP latency. RESULTS: TFT and TCS patients had a significantly longer MEP latency than healthy subjects. PCT in TFT patients was significantly longer than those in TCS patients or healthy subjects. Using the cutoff values for PCT, we were able to diagnose patients with TFT patients with a sensitivity of 72.0% and a specificity of 91.4%. CONCLUSION: Prolonged PCT in the MEP test may be a useful indicator for TFT and suggests that MEP may be used as an adjunct diagnostic tool for TFT.

Surgical outcomes of cervical myelopathy in patients with athetoid cerebral palsy.

PURPOSE: Surgical treatment for cervical myelopathy with athetoid cerebral palsy remains unestablished. Instrumented fusion is reported to have good clinical results; however, there are no data of decompression surgery for this pathology in recent years. This study aimed to assess the surgical outcomes of laminoplasty with or without posterior instrumented fusion for cervical myelopathy in patients with athetoid cerebral palsy. METHODS: A multi-centre surgical series of patients with cervical myelopathy and athetoid cerebral palsy were enrolled in this study. All patients showed symptoms and signs suggestive of cervical myelopathy and underwent laminoplasty with or without instrumented fusion. The Japanese Orthopaedic Association (JOA) score, Barthel index (BI), and changes in the C2-C7 sagittal Cobb angle in the lateral plain radiograph were analysed. RESULTS: There were 25 patients (16 men and 9 women; mean age, 54.4 ± 10.8 years) with cervical myelopathy and athetoid cerebral palsy who underwent surgical treatment. The mean follow-up period was 41.9 ± 35.6 months. Overall, the BI significantly improved after surgery, whereas the JOA score and C2-C7 angle did not improve postoperatively. The recovery rate of the JOA score in the laminoplasty group was significantly higher than that of the fusion group (P = 0.02). CONCLUSIONS: Cervical laminoplasty with or without instrumented fusion for treating cervical myelopathy due to athetoid cerebral palsy is effective in improving activities of daily living. Cervical laminoplasty may be an effective and less invasive surgical method for selective patients, especially for those with small involuntary movements and no remarkable cervical kyphosis nor instability.

Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis.

PURPOSE: Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. METHODS: Patients with de novo DLS, aged ≥ 65 years, who had LBP with visual analog scale (VAS) of ≥ 50 for ≥ 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. RESULTS: One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 ± 32.4 and 43.9 ± 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. CONCLUSION: Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.

Improving the quality of a recombinant rabbit monoclonal antibody against PLXDC2 by optimizing transient expression conditions and purification method.

Rabbit monoclonal antibodies (mAbs) have many advantages over mouse antibodies in biological research and diagnostics applications because they exhibit high affinity and specificity. However, the methods of recombinant rabbit mAb production have not been optimized to the same extent as techniques used to produce mouse and human mAbs. In this study, we sought to optimize the production of a recombinant rabbit mAb against human plexin domain containing protein 2 (PLXDC2), a known cell surface antigen, by culturing HEK293-6E cells transfected with antibody-encoding genes at two different temperatures and by purifying the end-product by three different chromatography methods. The quality and function of purified antibody preparations were checked by electrophoresis and western blot analysis. The secreted rabbit mAb produced by a combination of culturing at 32 °C, purification by ammonium sulfate fractionation, and diethylaminoethyl resin (DEAE) ion exchange chromatography was of high quality. In contrast, the antibody produced by the cells grown at 37 °C for 6 days after transfection and purified by Protein A/G affinity method was low quality. Hypothermic conditions during production reduced protein heterogeneity probably by favorably affecting the levels of glycosylation and aggregation. In particular, according to western blotting data, CIMmultus DEAE chromatography that utilizes monolithic columns not only excluded inferior charge variants resulting from nonspecific reactions but also yielded rabbit mAb that was of better quality than commercially available rabbit polyclonal antibodies. The combination of techniques suggested by us may be a general approach to enhance product quality of rabbit mAbs produced by transient expression systems.

Capto MMC mixed-mode chromatography of murine and rabbit antibodies.

Murine antibodies have weak affinity for Protein-A. Here, we have tested binding of murine monoclonal antibody (mAb) to Protein-A or Protein-A/Protein-G mixture under salting-out conditions. The addition of ammonium sulfate to HEK conditioned medium (CM) expressing murine mAb resulted in complete binding, leading to its elution by low pH or neutral arginine solution. Alternatively, a mixed-mode chromatography using Capto MMC resin was developed as a capture step. Binding of murine mAb occurred at neutral pH. The bound mAb was eluted with a gradient from 0.3 M NaCl to 0.3 M arginine/0.3 M NaCl at pH 7.0. The Capto MMC-purified murine mAb was further purified by hydroxyl apatite chromatography. Similarly, rabbit mAb was processed with some modifications. Binding of rabbit mAb to Capto MMC required a lower pH. Elution of the bound rabbit mAb was achieved by a gradient to 0.3 M NaCl, pH 7.0.

Differentiation of the Intradural Extramedullary Spinal Tumors, Schwannomas, and Meningiomas Utilizing the Contrast Ratio as a Quantitative Magnetic Resonance Imaging Method.

BACKGROUND: Schwannomas and meningiomas are the most common intradural extramedullary spinal tumors; however, differentiating between them using magnetic resonance imaging (MRI) is a frequent challenge. In this study, we aimed to investigate the use of the contrast ratio (CR) as a quantitative MRI method in the differentiation of schwannomas and meningiomas. METHODS: We analyzed the data of patients with intradural extramedullary spinal tumors who underwent surgery and were diagnosed with either schwannomas or meningiomas by histopathological analysis. Regions of interest were set for the entire spinal tumor on T2-weighted sagittal MRI. To obtain the CR values of spinal tumors (CRtumor), we used the signal intensity (SI) values of the tumor (SItumor) and spinal cord (SIcord) according to the following formula: [CRtumor = (SItumor-SIcord)/(SItumor+SIcord)]. RESULTS: The study included 50 patients (23 males and 27 females) with a mean age of 61.5 years old (11-85 years old). Histopathological analysis revealed that 33 and 17 patients were diagnosed with schwannomas and meningiomas, respectively. The mean CR values of the schwannomas and meningiomas were 0.3040 ± 0.1386 and 0.0173 ± 0.1929, respectively. The CR value of the schwannomas was statistically significantly higher than that of meningiomas (P < 0.01). The cutoff CR value obtained from the receiver operating characteristic curve was 0.143, with a specificity and sensitivity of 90.9% and 88.2%, respectively. Furthermore, the value for the area under the receiver operating characteristic curve was 0.925 (95% confidence interval: 0.852-0.998). CONCLUSIONS: The evaluation of CRs by using MRI to distinguish between schwannomas and meningiomas is a beneficial quantitative tool.

Evaluation of Epiconus and Conus Medullaris Disorders due to Thoracolumbar Vertebral Fracture using Motor Evoked Potentials.

STUDY DESIGN: A retrospective case-control study. OBJECTIVE: To characterize the motor evoked potential (MEP) when the epiconus or conus medullaris is compressed by a fracture of the T12 or L1 vertebra. SUMMARY OF BACKGROUND DATA: Although the characteristics of compressive cervical and thoracic myelopathy with transcranial magnetic stimulation MEP have been reported, the MEP parameters in compressive disorders of the epiconus and conus medullaris have not yet been characterized. METHODS: Twenty patients with T12 or L1 vertebral fractures who had lower extremity symptoms due to compression of the epiconus or conus medullaris were included. These patients were compared with 28 healthy controls and 32 patients with cervical spondylotic radiculopathy (CSR) without spinal cord compression. MEPs of abductor hallucis muscles were recorded using transcranial magnetic stimulation and electrical stimulation of the tibial nerve. MEP latency, central motor conduction time (CMCT), and peripheral conduction time (PCT) were evaluated. RESULTS: MEP latency, CMCT, and PCT were significantly longer in patients with fractures than in healthy controls and patients with CSR. MEP latency was most accurate for differentiating patients with fracture from healthy controls (cutoff value, 40.0 ms, sensitivity, 95.0%; specificity, 100%), and CMCT was most accurate for comparing patients with fracture and CSR (cutoff value, 15.5 ms, sensitivity, 80.0%; specificity, 93.8%). In the distinction between patients with fracture and CSR, 16 of the 20 patients with fracture exceeded the cutoff values for any of the parameters, and 12 of them exceeded the cutoff values for all parameters. There was no significant correlation between the linear distance from the most inferior end of the spinal cord to the site of compression and any of the MEP parameters. CONCLUSION: Both CMCT and PCT are often prolonged in compressive lesions of the epiconus and conus medullaris, and MEP latency and CMCT are useful in the diagnosis.

Differentiating Neurodegenerative Disease from Compressive Cervical Myelopathy Using Motor Evoked Potentials.

STUDY DESIGN: A retrospective case-control study. OBJECTIVE: To differentiate neurodegenerative diseases from compressive cervical myelopathy (CCM) using motor evoked potentials (MEPs). SUMMARY OF BACKGROUND DATA: When considering surgery for CCM, it may be necessary to differentiate the condition from a neurodegenerative disease. METHODS: A total of 30 healthy volunteers, 52 typical CCM patients with single-level compression of the spinal cord at C4-5 or C5-6, seven patients with amyotrophic lateral sclerosis (ALS), and 12 patients with demyelinating disease of the central nervous system (DDC), including 11 patients with multiple sclerosis and one patient with neuromyelitis optica spectrum disorder, formed our study population. MEPs were recorded from the bilateral abductor digiti minimi (ADM) and abductor hallucis (AH) muscles using transcranial magnetic stimulation and electrical stimulation of the ulnar and tibial nerves. Central motor conduction time (CMCT), peripheral conduction time, amplitude of MEPs, and frequency of F-waves were evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off value for distinguishing between CCM and ALS. RESULTS: Significant differences were observed in the amplitude of MEPs and frequency of F-waves evoked by peripheral nerve stimulation between patients with CCM and ALS. The MEP amplitude of AH was more accurate in differentiating between the two diseases compared to ADM (cut-off value, 11.2mV, sensitivity, 87.5%; specificity, 85.7%). All seven patients with ALS showed reduced frequency of F waves from ADM or AH, but none of the healthy volunteers or patients with other diseases demonstrated this finding. Moreover, there were no significant differences between CCM and DDC in any of the assessments. CONCLUSION: The amplitude of MEPs and frequency of F waves evoked by peripheral nerve stimulation could be helpful in differentiating ALS from CCM.

Foramen Magnum Decompression with Outer Dura Matter Layer Resection for Chiari Type I Malformation: Factors Correlated with Syrinx Reduction.

STUDY DESIGN: A retrospective cohort study. PURPOSE: We aimed to investigate the surgical results of foramen magnum decompression (FMD) to identify the potential factors associated with syrinx reduction in Chiari malformation type I (CMI). OVERVIEW OF LITERATURE: The predictive value of preoperative factors for syrinx reduction in patients with CMI remains debatable. METHODS: We enrolled patients who underwent microscopic FMD with outer dural layer resection for CMI. The distance from the tip of the cerebellar tonsil to the C2 vertebral endplate on sagittal magnetic resonance imaging (MRI) was defined as the tonsillar distance (TD). Patients who showed a >20% syrinx diameter reduction on the 1-year follow-up MRI were defined as the syrinx reduction group while the others were categorized in the syrinx nonreduction group. Patients with syringomyelia were categorized into the clinically improved and unimproved groups using the Chicago Chiari Outcome Scale. The imaging and clinical parameters were evaluated pre- and postoperatively. RESULTS: This study included 25 patients of whom 19 (76.0%) had syringomyelia. At the 1-year follow-up, the syrinx diameter had decreased in 11 patients (57.8%). The increased TD significantly differed between the syrinx reduction and nonreduction groups. At the 1-year follow-up, 12 and seven patients with syringomyelia were categorized into the clinically improved and unimproved groups, respectively. The clinically improved and unimproved groups showed significant differences in the mean age and increased TD. CONCLUSIONS: Postoperative syrinx reduction was significantly correlated with the upward shifting of the cerebellar tonsil in patients with CMI. Our quantitative evaluation of the alterations in hindbrain position after FMD was easily performed and reflects the clinical outcomes.

Differentiation Between Compressive Cervical and Thoracic Myelopathy Using the Central Motor Conduction Time Ratio.

PURPOSE: Thoracic myelopathy is a rare condition whose diagnosis is often missed or delayed. This study aimed to differentiate between cervical and thoracic myelopathy using motor-evoked potential testing. METHODS: The authors included 835 patients with compressive cervical myelopathy and 94 patients with compressive thoracic myelopathy. Myelopathy using motor-evoked potentials were recorded from the bilateral abductor digiti minimi and abductor hallucis muscles through transcranial magnetic stimulation. The peripheral conduction time was measured through electrical stimulation of the ulnar and tibial nerves; moreover, the central motor conduction time (CMCT) was calculated by subtracting the peripheral conduction time from the myelopathy using motor-evoked potential latency. RESULTS: The most accurate differentiation between compressive cervical myelopathy and compressive thoracic myelopathy was achieved by the CMCT ratios (CMCT-ADM:CMCT-AH; cutoff value of 0.490, sensitivity of 83.0%, and specificity of 80.5%). After excluding patients with compressive cervical myelopathy who had spinal cord compression at C6-7, the cutoff value was 0.490, with a sensitivity of 83.0% and specificity of 87.3%. CONCLUSIONS: Determining the CMCT ratio (cutoff value of 0.490) through motor-evoked potential testing could facilitate differentiation between compressive cervical myelopathy and compressive thoracic myelopathy.

Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including BQ.1.1, CA.3.1, CH.1.1, XBB.1.16, and XBB.1.5.

SARS-CoV-2 Omicron variant XBB.1.5 has shown extraordinary immune escape even for fully vaccinated individuals. There are currently no approved antibodies that neutralize this variant, and continued emergence of new variants puts immunocompromised and elderly patients at high risk. Rapid and cost-effective development of neutralizing antibodies is urgently needed. Starting with a single parent clone that neutralized the Wuhan-Hu-1 strain, antibody engineering was performed in iterative stages in real time as variants emerged using a proprietary technology called STage-Enhanced Maturation. An antibody panel that broadly neutralizes currently circulating Omicron variants was obtained by in vitro affinity maturation using phage display. The engineered antibodies show potent neutralization of BQ.1.1, XBB.1.16, and XBB.1.5 by surrogate virus neutralization test and pM KD affinity for all variants. Our work not only details novel therapeutic candidates but also validates a unique general strategy to create broadly neutralizing antibodies to current and future SARS-CoV-2 variants.