Efficacy of KPR-5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress-induced bladder overactivity in male rats.

AIMS: Chronic psychological stress aggravates lower urinary tract symptoms. Among others, water avoidance stress is a chronic psychological stressor that plays a causal role in the exacerbation and development of bladder dysfunction in rats. In this report, the effects of KPR-5714, which is a selective transient receptor potential melastatin 8 (TRPM8) antagonist, on bladder overactivity induced by water avoidance stress were examined. METHODS: Male rats were subjected to water avoidance stress for 2 h per day for 10 consecutive days. The effects of water avoidance stress on voiding behavior using metabolic cages and histological bladder changes were investigated in rats. The involvement of bladder C-fiber afferent on voiding frequency in rats exposed to water avoidance stress was assessed using capsaicin. The effects of KPR-5714 on storage dysfunction in rats subjected to water avoidance stress were examined. RESULTS: In voiding behavior measurements, water avoidance stress-induced storage dysfunction, causing a decrease in the mean voided volume and increasing voiding frequency. A comparison of bladders from normal rats and rats exposed to water avoidance stress showed no histological differences. Water avoidance stress-induced bladder overactivity was completely inhibited by pretreatment with capsaicin. KPR-5714 showed a tendency to increase the mean voided volume and significantly decreased the voiding frequency without affecting the total voided volume in these rats. CONCLUSION: The results suggest that KPR-5714 is a promising option for treating chronic psychological stress-induced bladder overactivity.

Influence of the Preoperative Duration of Symptoms on Patients' Clinical Outcomes after Minimally Invasive Surgery-Transforaminal Lumbar Interbody Fusion for Degenerative Lumbar Spinal Diseases.

Background and Objectives: The impact of the duration of symptoms (DOS) on postoperative clinical outcomes of patients with degenerative lumbar spinal diseases is important for determining the optimal timing of surgical intervention; however, the timing remains controversial. This prospective case−control study aimed to investigate the influence of the preoperative DOS on surgical outcomes in minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF). Materials and Methods: Patients who underwent single-level TLIF for lumbar degenerative diseases between 2017 and 2018 were reviewed. Only patients with full clinical data during the 1-year follow-up period were included. The patients were divided into two groups (DOS < 12 months, group S; DOS ≥ 12 months, group L). The clinical outcomes, including the Oswestry disability index (ODI) and visual analog scale (VAS) for lower back pain, leg pain, and numbness, were investigated preoperatively and at 1, 3, and 6 months, as well as 1 year, after surgery. Furthermore, postoperative patient satisfaction 1 year after surgery was also surveyed. Results: A total of 163 patients were assessed: 60 in group S and 103 in group L. No differences in baseline characteristics and clinical outcomes were found. The ODI and VAS significantly improved from the baseline to each follow-up period (all p < 0.01). Group S had significantly lower ODI scores at 3 months (p = 0.019) and 6 months (p = 0.022). In addition, group S had significantly lower VAS scores for leg pain at 3 months (p = 0.027). In a comparison between both groups, only the patients with cauda equina symptoms showed that ODI and leg pain VAS scores at 3 months after surgery were significantly lower in group S (19.9 ± 9.1 vs. 14.1 ± 12.5; p = 0.037, 7.4 ± 13.9 vs. 14.7 ± 23.1; p = 0.032, respectively). However, the clinical outcomes were not significantly different between both groups 1 year after surgery. Patient satisfaction was also not significantly different between both groups. Conclusions: Patients with a shorter DOS tended to have a significantly slower recovery; however, clinical outcomes 1 year after surgery were good, regardless of the DOS.

Spontaneous adenocarcinoma with giant cell formation in the accessory sex glands in a male Sprague-Dawley rat.

In this study, we report the features of an adenocarcinoma with giant cell formation spontaneously occurring in the accessory sex glands of a male 10-month-old Sprague-Dawley rat. A milky white mass was found in the region corresponding to the left seminal vesicle and the left coagulating gland. Histologically, tumor cells exhibited diverse growth patterns, including glandular/trabecular, cystic, and sheet-like growth areas. The tumor cells were pleomorphic, with round- or oval-shaped nuclei and abundant eosinophilic cytoplasm. Mitotic figures were occasionally observed. Giant cells were also prominent in the sheet-like growth area, with intracytoplasmic vacuoles containing eosinophilic material. The stroma was rich in collagen fibers and fibroblasts. Numerous inflammatory cells were observed in the glandular and cystic lumina and stroma. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and proliferating cell nuclear antigen. In the sheet-like growth area, some of the tumor cells and giant cells were positive for vimentin in the cytoplasm adjacent to the nucleus. Electron microscopy revealed that the tumor cells contained a small number of mitochondria and rough endoplasmic reticulum, and had no basement membrane or desmosome. The giant cells occasionally contained variably sized intracytoplasmic lumina and globular filamentous bodies, probably corresponding to vimentin. Considering these morphological features, the tumor was diagnosed as an adenocarcinoma with the formation of giant tumor cells originating from the male accessory sex glands.

Correction to: ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

The author "Ashish D. Diwan" receives educational consultant fees from Nuvasive Inc.

ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

PURPOSE: To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. METHODS: Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. RESULTS: In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. CONCLUSION: GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study.

PURPOSE: Palliative surgery for patients with spinal metastasis provides good clinical outcomes. However, there have been few studies on quality of life (QOL) and cost-utility of this surgery. We aimed to elucidate QOL and cost-utility of surgical treatment for spinal metastasis. METHODS: We prospectively analyzed 47 patients with spinal metastasis from 2010 to 2014 who had a surgical indication. Thirty-one patients who desired surgery underwent spinal surgery (surgery group). Sixteen patients who did not want to undergo spinal surgery (non-surgery group). The EuroQol 5D (EQ-5D) and relevant costs were measured at one, three, six, and 12 months after study enrollment. Health state values were obtained by Japanese EQ-5D scoring and quality-adjusted life years (QALY) gained were calculated for each group. Cost-utility was expressed as the incremental cost-utility ratio (ICUR). RESULTS: Health state values improved from 0.036 at study enrollment to 0.448 at 12 months in the surgery group, but deteriorated from 0.056 to 0.019 in the non-surgery group, with a significant difference between groups (P < 0.05). The mean QALY gained at 12 months were 0.433 in the surgery group and 0.024 in the non-surgery group. The mean total cost per patient in the surgery group was $25,770 compared with $8615 in the non-surgery group. The ICUR using oneyear follow-up data was $42,003/QALY gained. CONCLUSIONS: Surgical treatment for spinal metastases is associated with significant improvement in health state value. In orthopaedic surgery, an ICUR less than $50,000/QALY gained is considered acceptable cost-effectiveness. Our results indicate that surgical treatment could be cost-effective.

Surgical debridement with retention of spinal instrumentation and long-term antimicrobial therapy for multidrug-resistant surgical site infections after spinal surgery: a case series.

PURPOSE: Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI. METHODS: We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54-82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution. RESULTS: The median duration of follow-up was 868 (178-1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase-negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1-6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12-352) days and 336 (89-1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7-73) days, and the mean time for normalization of C-reactive protein was 54.5 (7-105) days. CONCLUSIONS: Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy.

Risk Factors for Nonunion After Nonoperative Treatment for Pediatric Lumbar Spondylolysis: A Retrospective Case-Control Study.

BACKGROUND: Pediatric lumbar spondylolysis, a stress fracture of the lumbar spine, frequently affects young athletes, and nonoperative treatment is often the first choice of management. Because the union rate in lumbar spondylolysis is lower than that in general fatigue fractures, identifying risk factors for nonunion is essential for optimizing treatment. PURPOSE: To determine the risk factors for nonunion after nonoperative treatment of acute pediatric lumbar spondylolysis through multivariate analysis. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: We analyzed 574 pediatric patients (mean age, 14.3 ± 1.9 years) with lumbar spondylolysis who underwent nonoperative treatment between 2015 and 2022. Nonoperative treatment included the elimination of sports activities, bracing, and weekly athletic rehabilitation, with follow-up computed tomography. Patient data, lesion characteristics, sports history, presence of spina bifida occulta at the lamina with a lesion or at the lumbosacral spine excluding the lesion level, and lumbosacral parameters were examined. Differences between the union and nonunion groups were investigated using multivariate analysis to determine the risk factors for nonunion. RESULTS: Of the 574 patients, 81.7% achieved bone union. Multivariate analysis revealed that an L5 lesion and the progression of the main and contralateral lesion stages were significant independent risk factors for nonunion. An L5 lesion had a lower union rate than non-L5 lesions. As the main lesion progressed, the likelihood of nonunion increased significantly, and the progression of the contralateral lesion also showed a similar trend. Spina bifida occulta and lumbosacral parameters were not significant predictors of nonunion in this study. CONCLUSION: We identified the L5 lesion level and the progression of the main and contralateral lesion stages as independent risk factors for nonunion in pediatric lumbar spondylolysis after nonoperative treatment. These findings aid in treatment decision-making. When bone union cannot be expected with nonoperative treatment, symptomatic treatment is required without prolonged external fixation and rest, and without aiming for bone union. Individualized treatment plans are crucial based on identified risk factors.

Clinical Features and Therapeutic Process of Sacral Fatigue Fractures in Adolescents.

BACKGROUND: Sacral fatigue fractures are a rare injury but should be considered as a differential diagnosis for low back and buttock pain in young adults. Collective reports are limited, most of which have focused on long-distance runners. PURPOSE: To investigate the characteristics of sacral fatigue fractures in adolescents. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We analyzed patient background characteristics, physical examination and imaging findings, and treatment courses of those diagnosed with sacral fatigue fractures using magnetic resonance imaging. RESULTS: Among 34 patients with sacral fatigue fractures, 15 and 19 were male and female patients, respectively, with an age range of 11 to 19 years (mean age, 15.0 years). Almost all patients were athletes, and 29 patients performed their sport ≥5 times a week. Long-distance runners were the most commonly affected, comprising 7 patients, and participants in other common sports such as baseball (6 patients), basketball (4 patients), and soccer (3 patients) were also affected. Physical examination revealed tension sign (Lasègue test) on the affected side in 6 patients and tight hamstrings in 24 patients. Imaging findings included 18 patients with right-side involvement, 12 with left-side involvement, and 4 with involvement on both sides. In 11 patients, spina bifida occulta was observed at S1 and 8 patients had a history of lumbar spondylolysis with 4 patients having concurrent sacral fatigue fractures. Physical therapy was performed concurrently with the cessation of exercise, and return to exercise was permitted if the pain had been relieved after 1 month. All patients returned to sports at a median of 48 days (range, 20-226 days) after symptom onset. However, 2 patients experienced recurrence (1 patient on the ipsilateral side and 1 patient on the contralateral side). CONCLUSION: Sacral stress fractures are not limited to long-distance runners in this population and can manifest as lower back pain or buttock pain in athletes participating in a variety of sports. Although the course of treatment was generally good, the possibility of recurrence must always be considered.

Rate and Duration of Bone Union for Conservative Treatment in Pediatric Lumbar Spondylolysis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To report the detailed bone fusion rates and duration of treatment in unilateral and bilateral cases of pediatric lumbar spondylolysis (LS). SUMMARY OF BACKGROUND DATA: Early diagnosis and optimal conservative management for LS are crucial for achieving bony healing without surgery. However, existing research on the conservative treatment of pediatric LS, particularly regarding bone union rates and treatment duration for each stage of bilateral spondylolysis, is limited. METHODS: We retrospectively analyzed 590 pediatric patients (522 boys and 68 girls) under 18 years of age diagnosed with LS and treated conservatively from 2015 to 2021. Diagnosis was based on computed tomography scans and magnetic resonance imaging findings, with stages classified as very early, early, progressive, or terminal. Patient background, sports history, level and stage of spondylolysis, presence of spina bifida occulta, bone union rate, duration of conservative treatment, and recurrence rate were retrospectively analyzed. RESULTS: The overall bone union rate was 81.9%, with a mean conservative treatment duration of 53.7 days. Unilateral LS cases showed decreased bone union rates with stage advancement (very early; 98.2%, early; 96.0%, progressive; 64.3%). Bilateral LS cases with progressive or terminal stage demonstrated low bone union rates (very early/very early; 100%, early/very early; 94.1%, progressive/very early; 66.7%, early/early; 82.9%, progressive/early; 32.3%, progressive/progressive; 23.7%, very early/terminal; 0%, early/terminal; 50.0%, progressive/terminal; 11.1%). The duration of conservative treatment extended as the stage of the main and contralateral lesions progressed, ranging from 39.1 days (very early/none) to 105 days (progressive/terminal). Recurrence rate after bone fusion was 16.6%, with no differences based on lesion stage. CONCLUSION: In this series of 590 patients, conservative treatment yielded high bone union rates for pediatric LS. However, union rates decreased with stage advancement, especially in bilateral cases. These findings provide valuable insights for prognosticating natural history and outcome regarding LS treatment, bone union and return to activity.

Preoperative Low Back Pain Affects Postoperative Patient Satisfaction Following Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery.

STUDY DESIGN: A single-center retrospective study. PURPOSE: To research the predictive factors associated with postoperative patient satisfaction 1 year after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), a minimally invasive procedure for lumbar degenerative disease. OVERVIEW OF LITERATURE: There have been reports of numerous variables influencing patient satisfaction with lumbar surgery; however, there have been few investigations on MIS are limited. METHODS: This study included 229 patients (107 men and 122 women; mean age, 68.9 years) who received one or two levels of MISTLIF, and the patient's age, gender, disease, paralysis, preoperative physical functions, duration of symptom(s), and surgery-associated factors (waiting for surgery, number of surgical levels, surgical time, and intraoperative blood loss) were studied. Radiographic characteristics and clinical outcomes such as Oswestry Disability Index (ODI) scores and Visual Analog Scale (VAS; 0-100) ODI scores for low back pain, leg pain, and numbness were studied. One year following surgery, patient satisfaction (defined as satisfaction for surgery and for present condition; 0-100) was assessed using VAS and its relationships with investigation factors were examined. RESULTS: The mean VAS scores of satisfaction for surgery and for present condition were 88.6 and 84.2, respectively. The results of multiple regression analysis showed that preoperative adverse factors of satisfaction for surgery were being elderly (ß =-0.17, p =0.023), high preoperative low back pain VAS scores (ß =-0.15, p =0.020), and postoperative adverse factors were high postoperative ODI scores (ß =-0.43, p <0.001). In addition, the preoperative adverse factor of satisfaction for present condition was high preoperative low back pain VAS scores (ß =-0.21, p =0.002), and postoperative adverse factors were high postoperative ODI scores (ß =-0.45, p <0.001) and high postoperative low back pain VAS scores (ß =-0.26, p =0.001). CONCLUSIONS: According to this study, significant preoperative low back pain and high postoperative ODI score after surgery are linked to patient unhappiness.

Protective Effects of Growth Differentiation Factor-6 on the Intervertebral Disc: An In Vitro and In Vivo Study.

Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1ß (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1ß stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.

Discrimination of ranitidine hydrochloride crystals using X-ray micro-computed tomography for the evaluation of three-dimensional spatial distribution in solid dosage forms.

A non-destructive discrimination method for crystals in solid dosage drug forms was first developed using a combination of Raman spectroscopy and X-ray micro-computed tomography (X-ray CT). Identification of the crystal form of an active pharmaceutical ingredient (API) at the appropriate pharmaceutical dosage is crucial, as the crystal form is a determinant of the quality and performance of the final formulation. To develop a non-destructive analytical methodology for the discrimination of solid API crystals in a solid dosage form, we utilized a combination of Raman spectroscopy and X-ray CT to differentiate between ranitidine crystal polymorphs (forms 1 and 2) in tablet formulations containing three excipients. The difference in electron density correlated with the true density between ranitidine polymorphs, thereby enabling the discrimination of crystal forms and visualization of their three-dimensional spatial localization inside the tablets through X-ray CT imaging. Furthermore, X-ray CT imaging revealed that the crystal particles were of varying densities, sizes, and shapes within the same batch. These findings suggest that X-ray CT is not only an imaging tool but also a unique method for quantitative physicochemical characterization to study crystal polymorphs and solid dosage forms.

A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system.

Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM-CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM-CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA-MB-231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM-CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p < 0.05). Local administration of GM-CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM-CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP.

Delayed notochordal cell disappearance through integrin α5ß1 mechanotransduction during ex-vivo dynamic loading-induced intervertebral disc degeneration.

The loss of nucleus pulposus (NP) notochordal cells is one of the key initial hallmarks of age-related intervertebral disc degeneration. Although the transmembrane mechanoreceptor integrin α5ß1 is important in the process of disc degeneration, the relationship between integrin α5ß1 and notochordal cell disappearance remains unclear. The purpose of this study was to elucidate the role of integrin α5ß1 in the homeostasis of notochordal cells using an ex-vivo dynamic loading culture system that we developed. Rat tail functional spinal units (n = 80 from 40 rats) were cultured under unloading or 1.3-MPa, 1.0-Hz dynamic compressive loading for 48 or 144 h with or without an integrin α5ß1 inhibitor. Disc histomorphology, cell viability, apoptosis, senescence, and phenotypic expression were investigated. Consequently, histological degenerative disc changes with decreased cell viability and increased cell apoptosis and senescence were observed with an extended loading duration. Immunofluorescence revealed that the expression of notochordal cell markers, CD24 and brachyury, and chondrocyte markers, collagen type II and SRY-box 9, declined with loading. In particular, reduction in notochordal cell marker expression was more dramatic than that in chondrocyte marker expression. Apoptotic terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was also higher in brachyury-positive notochordal cells. Furthermore, all these changes were delayed by inhibiting integrin α5ß1. Findings of our dynamic loading regimen with a relatively high pressure suggest reproducibility of the cellularity and phenotypic disappearance of NP notochordal cells during adolescence, the susceptibility of notochordal cells to mechanical stimuli partially through the integrin α5ß1 pathway, and future potential treatment of integrin regulation for intervertebral disc disease.

Surgical outcomes and risk factors for poor outcomes in patients with cervical spine metastasis: a prospective study.

BACKGROUND: Few studies have addressed the impact of palliative surgery for cervical spine metastasis on patients' performance status (PS) and quality of life (QOL). We investigated the surgical outcomes of patients with cervical spine metastasis and the risk factors for a poor outcome with a focus on the PS and QOL. METHODS: We prospectively analyzed patients with cervical spine metastasis who underwent palliative surgery from 2013 to 2018. The Eastern Cooperative Oncology Group PS (ECOGPS) and EuroQol 5-Dimension (EQ5D) score were assessed at study enrollment and 1, 3, and 6 months postoperatively. Neurological function was evaluated with Frankel grading. Univariate and multivariate analyses were performed to identify the risk factors for a poor surgical outcome, defined as no improvement or deterioration after improvement of the ECOGPS or EQ5D score within 3 months. RESULTS: Forty-six patients (mean age, 67.5 ± 11.7 years) were enrolled. Twelve postoperative complications occurred in 11 (23.9%) patients. The median ECOGPS improved from PS3 at study enrolment to PS2 at 1 month and PS1 at 3 and 6 months postoperatively. The mean EQ5D score improved from 0.085 ± 0.487 at study enrolment to 0.658 ± 0.356 at 1 month and 0.753 ± 0.312 at 3 months. A poor outcome was observed in 18 (39.1%) patients. The univariate analysis showed that variables with a P value of < 0.10 were sex (male), the revised Tokuhashi score, the new Katagiri score, the level of the main lesion, and the Frankel grade at baseline. The multivariate analysis identified the level of the main lesion (cervicothoracic junction) as the significant risk factor (odds ratio, 5.00; P = 0.025). CONCLUSIONS: Palliative surgery for cervical spine metastasis improved the PS and QOL, but a cervicothoracic junction lesion could be a risk factor for a poor outcome.

Postoperative sagittal alignment of congenital thoracolumbar to lumbar kyphosis or kyphoscoliosis: a minimum 10-year follow-up study.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To elucidate the postoperative course of sagittal alignment in patients with congenital thoracolumbar to lumbar kyphosis or kyphoscoliosis. Acquisition of acceptable sagittal alignment is essential to treat spinal deformity. Little evidence exists regarding long-term surgical outcomes on sagittal alignment in congenital kyphosis or kyphoscoliosis. METHODS: Sixteen consecutive patients (mean age 10.5 ± 3.5 years) with congenital kyphosis or kyphoscoliosis who underwent vertebra resection and osteotomy with instrumentation by single posterior or combined anterior and posterior approach were included. Preoperative radiographs identified kyphosis in 3 patients and kyphoscoliosis in 13 patients. All patients had clinical and radiologic follow-up for > 10 years (mean 16.3 ± 4.0 years). RESULTS: Segmental kyphosis was significantly improved from 33.9° ± 20.1° to 14.9° ± 17.6° by surgery and was finally maintained at 16.8° ± 22.2° and sagittal vertical axis (SVA) of 13.1 ± 33.7 mm at preoperation and 18.3 ± 22.1 mm at postoperation significantly increased to 26.8 ± 45.7 mm during follow-up. Of the 16 patients, 5 (31%) were identified as those with SVA > 40 mm, and SVA increases > 30 mm during follow-up. In patients with sagittal malalignment, radiographs demonstrated decreased lumbar lordosis at the lower foundation from 28.8° ± 39.0° to 17.0° ± 17.6°, significant increased pelvic tilt from 25.8° ± 5.4° to 37.4° ± 7.4° during follow-up (p < 0.05), and larger residual segmental kyphosis than those in the 11 patients without sagittal malalignment with statistical significance. Of the five cases, progression of local kyphosis (one case) and sagittal decompensation, including decreased lumbar lordosis with disc degeneration (four cases), increased pelvic tilt (three cases), or proximal junctional kyphosis (two cases), were observed. CONCLUSION: Based on this > 10-year follow-up study, residual kyphosis and sagittal decompensation are revealed to be risk factors for postoperative sagittal malalignment in patients with congenital thoracolumbar to lumbar kyphosis or kyphoscoliosis. LEVEL OF EVIDENCE: Level IV, case series.

Prospective cohort study of surgical outcome for spinal metastases in patients aged 70 years or older.

AIMS: With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. METHODS: We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected. RESULTS: In total, 65 patients were aged < 70 years (mean 59.6 years; 32 to 69) and 36 patients were aged ≥ 70 years (mean 75.9 years; 70 to 90). In both groups, the PS improved from PS3 to PS1 by spine surgery, the mean BI improved from < 60 to > 80 points, and the mean EQ-5D score improved from 0.0 to > 0.7 points. However, no significant differences were found in the improvement rates and values of the PS, BI, and EQ-5D score at any time points between the two groups. The PS, BI, and EQ-5D score improved throughout the follow-up period in approximately 90% of patients in each group. However, the improved PS, BI, and EQ-5D scores subsequently deteriorated in some patients, and the redeterioration rate of the EQ-5D was significantly higher in patients aged ≥ 70 than < 70 years (p = 0.027). CONCLUSION: Palliative surgery for spinal metastases improved the PS, activities of daily living, and quality of life, regardless of age. However, clinicians should be aware of the higher risk of redeterioration of the quality of life in advanced-age patients. Cite this article: Bone Joint J 2020;102-B(12):1709-1716.

Improved bone bonding of hydroxyapatite spacers with a high porosity in a quantitative computed tomography-image pixel analysis: A prospective 1-year comparative study of the consecutive cohort undergoing double-door cervical laminoplasty.

Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P < .01), indicating bone absorption. This showed no significant difference between the HA spacers (P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers (P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up.

Reduced nucleotomy-induced intervertebral disc disruption through spontaneous spheroid formation by the Low Adhesive Scaffold Collagen (LASCol).

Back pain is a global health problem with a high morbidity and socioeconomic burden. Intervertebral disc herniation and degeneration are its primary cause, further associated with neurological radiculopathy, myelopathy, and paralysis. The current surgical treatment is principally discectomy, resulting in the loss of spinal movement and shock absorption. Therefore, the development of disc regenerative therapies is essential. Here we show reduced disc damage by a new collagen type I-based scaffold through actinidain hydrolysis-Low Adhesive Scaffold Collagen (LASCol)-with a high 3D spheroid-forming capability, water-solubility, and biodegradability and low antigenicity. In human disc nucleus pulposus and annulus fibrosus cells surgically obtained, time-dependent spheroid formation with increased expression of phenotypic markers and matrix components was observed on LASCol but not atelocollagen (AC). In a rat tail nucleotomy model, LASCol-injected and AC-injected discs presented relatively similar radiographic and MRI damage control; however, LASCol, distinct from AC, decelerated histological disc disruption, showing collagen type I-comprising LASCol degradation, aggrecan-positive and collagen type II-positive endogenous cell migration, and M1-polarized and also M2-polarized macrophage infiltration. Reduced nucleotomy-induced disc disruption through spontaneous spheroid formation by LASCol warrants further investigations of whether it may be an effective treatment without stem cells and/or growth factors for intervertebral disc disease.