Methods: This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results: Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

STUDY DESIGN: Retrospective observational study. PURPOSE: We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. METHODS: Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland–Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. RESULTS: Sarcopenia (SMI <5.46) was observed in nine subjects (26.5%). Compared with normal subjects (SMI >6.12), RDQ was significantly higher in subjects with sarcopenia (p=0.04). RDQ was significantly negatively correlated with SMI (r=−0.42, p<0.05). There was a significant positive correlation between postoperative RDQ and pelvic tilt (PT; r=0.41, p<0.05). SMI and PT were significantly negatively correlated (r=−0.39, r<0.05). CONCLUSIONS: Good postoperative outcomes were negatively correlated with low preoperative appendicular muscle mass, suggesting that postoperative outcomes were inferior in cases of decreased appendicular muscle mass (sarcopenia). Posterior PT due to decreased limb muscle mass may contribute to postoperative back pain, showing that preoperatively reduced limb muscle mass and posterior PT are predictive factors in the persistence of postoperative low back pain.
Absorptiometry, Photon ; Arm ; Asian Continental Ancestry Group ; Back Pain ; Bone Density ; Extremities ; Female ; Health Services Needs and Demand ; Humans ; Leg ; Low Back Pain ; Muscle, Skeletal ; Observational Study ; Orthopedics ; Retrospective Studies ; Sarcopenia ; Spinal Stenosis ; Visual Analog Scale

STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to examine changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a 10-year follow-up. OVERVIEW OF LITERATURE: Extreme lateral interbody fusion provides minimally invasive treatment of the lumbar spine; this anterior fusion without direct posterior decompression, so-called indirect decompression, can achieve pain relief. Anterior fusion may restore disc height, stretch the flexure of the ligamentum flavum, and increase the spinal canal diameter. However, changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a long follow-up have not yet been reported. METHODS: We evaluated 10 patients with L4 spondylolisthesis who underwent stand-alone anterior interbody fusion using the iliac crest bone. Magnetic resonance imaging was performed 10 years after surgery. The cross-sectional area (CSA) of the dural sac and the ligamentum flavum at L1–2 to L5–S1 was calculated using a Picture Archiving and Communication System. RESULTS: Spinal fusion with correction loss (average, 4.75 mm anterior slip) was achieved in all patients 10 years postsurgery. The average CSAs of the dural sac and the ligamentum flavum at L1–2 to L5–S1 were 150 mm² and 78 mm², respectively. The average CSA of the ligamentum flavum at L4–5 (30 mm²) (fusion level) was significantly less than that at L1–2 to L3–4 or L5–S1. Although patients had an average anterior slip of 4.75 mm, the average CSA of the dural sac at L4–5 was significantly larger than at the other levels. CONCLUSIONS: Spinal stability induced a lumbar ligamentum flavum change and a sustained remodeling of the spinal canal, which may explain the long-term pain relief after indirect decompression fusion surgery.
Decompression* ; Follow-Up Studies ; Humans ; Ligamentum Flavum* ; Magnetic Resonance Imaging ; Retrospective Studies ; Spinal Canal ; Spinal Fusion ; Spine ; Spondylolisthesis

STUDY DESIGN: Observational study. PURPOSE: To assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD). OVERVIEW OF LITERATURE: Low back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial. METHODS: Using the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels. RESULTS: A gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002). CONCLUSIONS: These results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.
Dichlorodiphenyldichloroethane ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-6 ; Intervertebral Disc Degeneration* ; Intervertebral Disc* ; Leg ; Low Back Pain ; Magnetic Resonance Imaging ; Nerve Growth Factor ; Observational Study ; Tumor Necrosis Factor-alpha

STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. OVERVIEW OF LITERATURE: PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. METHODS: PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at −80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. RESULTS: Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. CONCLUSIONS: Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.
Blood Preservation ; Flow Cytometry ; Freeze Drying ; Healthy Volunteers ; Humans* ; Intercellular Signaling Peptides and Proteins ; Pathology ; Platelet Activation ; Platelet Count ; Platelet-Rich Plasma* ; Regeneration

STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. METHODS: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. RESULTS: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). CONCLUSIONS: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.
Animals ; Back Pain ; Calcitonin Gene-Related Peptide ; Cytokines ; Diagnosis-Related Groups ; Endothelial Growth Factors ; Ganglia ; Ganglia, Spinal* ; Humans ; Intervertebral Disc* ; Low Back Pain ; Models, Animal ; Needles ; Neuropeptides* ; Punctures ; Rats* ; Rats, Sprague-Dawley ; Sodium ; Sodium Chloride ; Spinal Nerve Roots* ; Vascular Endothelial Growth Factor A*

STUDY DESIGN: Retrospective case series. PURPOSE: The purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis. OVERVIEW OF LITERATURE: Clinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years. METHODS: We treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 µg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery. RESULTS: We followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p>0.05). CONCLUSIONS: This study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.
Female ; Humans ; Osteoporosis ; Osteoporosis, Postmenopausal* ; Parathyroid Hormone ; Retrospective Studies ; Risedronate Sodium ; Spine ; Spondylolisthesis ; Teriparatide*

Purpose：This study investigated the current state of medical care and home palliative care for terminally ill cancer patients in Japan. Methods：We conducted a retrospective questionnaire study of 352 cancer patients who received home palliative care from 6 specialized home care clinics and discontinued home care or died from January to June in 2012. Results：The questionnaire was answered by 290 patients〔165 men（57％）, mean age：72±13 years〕who started home palliative care after completing cancer treatment. Home visits from nurses were used by 238 patients（98％）and 95 patients（39％）used home care workers. Within a month before discontinuation of home care or death, 72 patients（30％）received fluid therapy and 127 patients（52％）received strong opioids. The outcome of home palliative care was death at home in 242 patients（83％）and discontinuation of home care in 48 patients（17％）. The reason for discontinuation was family physical and mental problems or physical problems of the patient. Conclusion：This study demonstrated the current state of home palliative care by specialized home care clinics.

Objectives:To determine the factors influencing death or the cessation of palliative care in home-based setting among patients with cancer. Methods:We included 352 terminally ill patients with cancer who received home-based palliative care from six specialized palliative care clinics. We reviewed the medical charts when patients died at home or chose to stop home care. Results:A total of 82％ of participants died at home, and 18％ chose to stop home care. Multiple logistic regression analysis revealed five independent factors that affected cessation of home-based palliative care:patient and informal caregiver preferences for the place of death not to be at home［odds ratio, 10.1（95％ Confidential interval, 2.5-40.9）and 51.9（11.9-226.6）, respectively］or uncertain preferences［5.0（1.3-19.4）, 10.8（2.3-50.5）］;anxiety and depression among informal caregiver［4.1（1.2-13.9）］;lower frequency of informal care［6.8（2.0-23.4）］;and history of admittance to hospital during home care［11.6（4.0-33.9）］. Conclusion:We revealed independent factors influencing death or the cessation of palliative care in home-based settings among patients with cancer. Our findings suggest the importance of providing support for decision making about the place of death and hospital admission, and psychosocial support for informal caregiver to ensure home death consistent with patient preference.

OBJECTIVESTo investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) in children and its relationship to metabolic syndrome, insulin resistance, and waist circumference (WC).

METHODSThis was a population-based cross-sectional, case-control study. Cases were selected among students of a primary and junior high school, respectively, and age- and sex-matched control subjects were selected randomly (ratio of cases to control subject was 37:113).

RESULTSOf the 846 students, aged between 6 and 15 years, enrolled in the study and screened by ultrasonography, 37 children were diagnosed as having NAFLD (score >/= 1). There was a significant sex difference in the prevalence of NAFLD(P = 0.003). The trend test revealed a strong dose-response relationship (P < 0.001) between pediatric NAFLD and the number of the proposed components of pediatric metabolic syndrome in Japan (MetS-JC), such as a clustering of the components of MetS-JC. Additionally, the linear trend of the odds ratios (ORs) with increasing percentile of the homeostasis model assessment-insulin resistance (HOMA-IR) was statistically significant (P < 0.001). However, when WC was added to the logistic model, the ORs were no longer significant, whereas WC turned out to be an independent risk factor for NAFLD regardless of the HOMA-IR index.

CONCLUSIONThe prevalence of NAFLD in children and adolescents is closely related to metabolic syndrome, insulin resistance, and WC.