Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation.

Background and Objectives: Intradiscal injection of Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, is employed as a minimally invasive treatment for lumbar disc herniation (LDH) and represents a promising option between conservative treatment and surgical intervention. Since its 2018 approval in Japan, multiple single-site trails have highlighted its effectiveness, however, the effect of LDH types, and influences of patient age, sex, etc., on treatment success remains unclear. Moreover, data on teenagers and elderly patients has not been reported. In this retrospective multi-center study, we sought to classify prognostic factors for successful condoliase treatment for LDH and assess its effect on patients < 20 and ≥70 years old. Materials and Methods: We reviewed the records of 137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a "group-A" category if a ≥50% improvement in baseline leg pain VAS was observed or "group-N" if VAS leg pain improved <50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle > 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial.

Radiological features of cervical spine in dropped head syndrome: a matched case-control study.

PURPOSE: Dropped head syndrome (DHS) is presumably caused by focal myopathy in the cervical posterior muscles; however, distinguishable radiological features of the cervical spine in DHS remain unidentified. This study investigated the radiological features of the cervical spine in dropped head syndrome. METHODS: The records of DHS patients and age- and sex-matched cervical spondylotic myelopathy (CSM) patients were reviewed. Cervical spinal parameters (C2-7, C2-4, and C5-7 angles) were assessed on lateral cervical spine radiographs. Quantitative radiographic evaluation of cervical spine degeneration was performed using the cervical degenerative index (CDI), which consists of four elements: disk space narrowing (DSN), endplate sclerosis, osteophyte formation, and listhesis. RESULTS: Forty-one DHS patients were included. Statistically significant differences were noted between the upper and lower cervical spine in the sagittal angle parameters on the neutral, flexion, and extension radiographs in DHS group, whereas no significant differences were observed in CSM group. CDI comparison showed significantly higher scores of DSN in C3/4, C4/5, C5/6, and C6/7; sclerosis in C5/6 and C6/7; and osteophyte formation in C4/5, C5/6, and C6/7 in DHS group than in CSM group. Comparison of listhesis scores revealed significant differences in the upper levels of the cervical spine (C2/3, C3/4, and C4/5) between two groups. CONCLUSION: Our results demonstrated that the characteristic radiological features in the cervical spine of DHS include lower-level dominant severe degenerative change and upper-level dominant spondylolisthesis. These findings suggest that degenerative changes in the cervical spine may also play a role in the onset and progression of DHS.

Impact of Spinopelvic sagittal alignment on the surgical outcomes of dropped head syndrome: a multi-center study.

BACKGROUND: Most of the previous studies about the surgical treatment of dropped head syndrome (DHS) are small case series, and their primary outcome measures were cervical alignment parameters. Therefore, little is known about the associations between pre- and postoperative global sagittal alignment in the whole spine and the clinical outcomes of the surgical treatment of DHS. In this study, we investigated the surgical outcomes of DHS, including correction of cervical and global spinal sagittal alignment. METHODS: This study was a retrospective observational study. Fifteen patients with DHS who had undergone correction surgery were enrolled. Surgical outcomes, including complications and implant failures, were investigated. We assessed cervical alignment parameters as well as spinopelvic global alignment parameters, including pelvic incidence (PI), lumbar lordosis (LL), and C7-sacral sagittal vertical axis (SVA). We examined the changes in these parameters using pre- and posoperative whole spine lateral radiographs. The parameters were compared between the failure and nonfailure groups. RESULTS: Recurrence of sagittal imbalance and horizontal gaze difficulty was observed in 6 cases (40%). In all, 3 cases (20%) exhibited a distal junctional failure and required multiple surgeries with extension of fusion. Of all the radiographic parameters compared between the failure and nonfailure groups, significant differences were only observed in pre and postoperative SVA and PI-LL. CONCLUSIONS: Our results suggest that the global sagittal alignment parameters, including PI-LL and SVA, were different between the patients with failure and non failure, and these parameters might have notable impacts on surgical outcomes. Surgeons should consider PI-LL and SVA while determining the surgical course for patients with DHS.

Lateral lumbar interbody fusion in revision surgery for restenosis after posterior decompression.

OBJECTIVE: The purpose of this study was to compare the clinical results of revision interbody fusion surgery between lateral lumbar interbody fusion (LLIF) and posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF) with propensity score (PS) adjustments and to investigate the efficacy of indirect decompression with LLIF in previously decompressed segments on the basis of radiological assessment. METHODS: A retrospective study of patients who underwent revision surgery for recurrence of neurological symptoms after posterior decompression surgery was performed. Postoperative complications and operative factors were evaluated and compared between LLIF and PLIF/TLIF. Moreover, postoperative improvement in cross-sectional areas (CSAs) in the spinal canal and intervertebral foramen was evaluated in LLIF cases. RESULTS: A total of 56 patients (21 and 35 cases of LLIF and PLIF/TLIF, respectively) were included. In the univariate analysis, the LLIF group had significantly more endplate injuries (p = 0.03) and neurological deficits (p = 0.042), whereas the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), surgical site infections (SSIs) (p = 0.02), and estimated blood loss (EBL) (p < 0.001). After PS adjustments, the LLIF group still showed significantly more endplate injuries (p = 0.03), and the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), EBL (p < 0.001), and operating time (p = 0.04). The PLIF/TLIF group showed a trend toward a higher incidence of SSI (p = 0.10). There was no statistically significant difference regarding improvement in the Japanese Orthopaedic Association scores between the 2 surgical procedures (p = 0.77). The CSAs in the spinal canal and foramen were both significantly improved (p < 0.001). CONCLUSIONS: LLIF is a safe, effective, and less invasive procedure with acceptable complication rates for revision surgery for previously decompressed segments. Therefore, LLIF can be an alternative to PLIF/TLIF for restenosis after posterior decompression surgery.

A new method for measuring osteoclast formation by electrical impedance.

Osteoclasts are important target cells for osteoporosis treatment. Recently, a real-time cell analysis (RTCA) system was developed to observe cell morphology and adhesion; however, the use of RTCA to study osteoclastogenesis has not been reported. Here, we investigated whether osteoclast formation could be monitored in real-time using RTCA. The cell index determined via electrical impedance using RTCA, and the number of osteoclasts exhibited a significant positive correlation. RTCA was useful for determining the effect of (-)-epigallocatechin-3-gallate on the inhibition of bone resorption. We established a new method of measuring osteoclast formation in real-time using RTCA.

A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella.

BACKGROUND: Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. RESULTS: Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation. CONCLUSIONS: We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.

The effect of denosumab on pedicle screw fixation: a prospective 2-year longitudinal study using finite element analysis.

BACKGROUND: Pedicle screw loosening is a major complication following spinal fixation associated with osteoporosis in elderly. However, denosumab is a promising treatment in patients with osteoporosis. The effect of denosumab on pedicle screw fixation is unknown. Therefore, we investigated whether denosumab treatment improves pedicle screw fixation in elderly patients with osteoporosis. METHODS: This was a 2-year prospective open-label study. From February 2015 to January 2016, we included 21 patients with postmenopausal osteoporosis who received initial denosumab treatment. At baseline, 12 months, and 24 months, we measured volumetric bone mineral density (BMD) using quantitative computed tomography (QCT) and performed CT-based finite element analysis (FEA). Finite element models of L4 vertebrae were created to analyze the bone strength and screw fixation. RESULTS: BMD increased with denosumab treatment. FEA revealed that both pullout strength of pedicle screws and compression force of the vertebra increased significantly at 12 and 24 months following denosumab treatment. Notably, pullout strength showed a stronger correlation with three-dimensional volumetric BMD around pedicle screw placement assessed by QCT (r = 0.83, at 24 months) than with two-dimensional areal BMD assessed by dual energy X-ray absorptiometry (r = 0.35, at 24 months). CONCLUSION: To our knowledge, this is the first study to reveal that denosumab treatment achieved strong pedicle screw fixation with an increase in BMD around the screw assessed by QCT and FEA; therefore, denosumab could be useful for osteoporosis treatment during spinal surgery in elderly patients with osteoporosis.

The Utility of the Energy Subtraction Method for Thoracic Spine Radiography in Clinical Practice: An Analysis of 25 Patients With Multiple Myeloma.

Interpretation of thoracic spine radiographs is difficult because they cannot clearly depict the vertebrae due to overlap with soft tissues. This study aimed to evaluate whether thoracic spine radiographs obtained using the energy subtraction method could improve the accuracy of a diagnosis of thoracic osteolytic lesions. The authors analyzed 300 thoracic vertebrae from 25 patients with multiple myeloma who underwent thoracic spine radiography. All patients underwent thoracic spine radiography with 2 views. Two sets of images were prepared: computed radiography images (CR images) acquired using conventional processing parameters; and processed images for specifically visualizing bone, using the energy subtraction method (ES images). The CR images (CR group) and paired CR and ES images (CR+ES group) were interpreted in parallel by 5 orthopedic surgeons. The presence of osteolytic lesions was evaluated for each of the 12 thoracic vertebrae, and the sensitivity and specificity of the method were compared with computed tomography (CT), which is considered the gold standard. Subgroup analysis was also performed based on location. Osteolytic lesions were found on CT in 28 (9.3%) vertebrae of 12 patients. The overall sensitivities and specificities of the CR and CR+ES groups were 17.2% and 54.3%, respectively, and 95.6% and 98.0%, respectively, with statistically significant differences. Subgroup analysis showed particular improvement in the sensitivity for the CR+ES group in the middle thoracic spine compared with that at other locations. Thoracic spine radiographs generated using this method may improve the accuracy of diagnosis of thoracic osteolytic lesions. [Orthopedics. 2021;44(1):e31-e35.].

Risk factors predicting osteosarcopenia in postmenopausal women with osteoporosis: A retrospective study.

There is growing interest in "osteosarcopenia" as the coexistence of osteoporosis and sarcopenia exacerbates negative outcomes. However, limited information is available regarding the risk factors of osteosarcopenia development in patients with osteoporosis. Therefore, we retrospectively reviewed 276 consecutive patients with postmenopausal osteoporosis who regularly visited Showa University Hospital. Patients were eligible for the study if they were ≥65 years of age and underwent dual-energy X-ray absorptiometry, blood sampling, and physical performance assessment. Patients were divided into the osteosarcopenia and osteoporosis alone groups according to the diagnostic criteria of the Asian Working Group for Sarcopenia. Of the 276 patients with osteoporosis, 54 patients (19.6%) had osteosarcopenia. Patients in the osteosarcopenia group had a greater risk of frailty than did those in the osteoporosis alone group (odds ratio 2.33; 95% confidence interval, 1.13-4.80, P = 0.028). Low body mass index seemed to be the strongest factor related to the development of osteosarcopenia, and none of the patients in the osteosarcopenia group were obese (BMI ≥27.5 kg/m2). Multiple logistic analyses revealed that patients aged 65-74 years who had comorbidities such as kidney dysfunction and high levels of HbA1c were at risk of developing osteosarcopenia. Thus, we strongly recommend the assessment of the key components of the diagnosis of osteosarcopenia in an osteoporosis clinic for patients with low body mass index. Furthermore, appropriate assessments, including comorbidities, will help in identifying patients at greater risk of developing osteosarcopenia.

Analysis of three-dimensional bone mineral density and bone strength measured by quantitative computed tomography following denosumab discontinuation in a patient with postmenopausal osteoporosis.

Discontinuation of denosumab during osteoporosis treatment leads to rapid loss of bone mineral density and induces a bone turnover rebound effect. Previous studies have reported analysis based on dual-energy X-ray absorptiometry scanning (DXA). Here, we report the first case involving analysis of three-dimensional bone mineral density and bone strength, measured by quantitative computed tomography (QCT) after discontinuation of denosumab. An 82-year-old woman who discontinued denosumab because of patient's wish was administered the fifth dose after a gap of 14 months. Her bone mineral density evaluated by DXA and QCT, bone strength, and bone turnover marker levels showed significant rebound phenomenon. The levels of the cortical parameters of the hip were also decreased indicating an increased risk of femoral fractures after denosumab interruption. Our case highlights the increased risk of fractures after discontinuation of denosumab. Therefore, denosumab must be used judiciously without interruption in the dosage schedule.