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1.  Elderly onset intramedullary epidermoid cyst in the conus medullaris: a case report 
Introduction
Epidermoid cysts are known as embryonic or acquired ectopic aberrations of the ectoderm. To the best of our knowledge, there are only a few reports of elderly onset intramedullary epidermoid cysts. We report a case of elderly onset intramedullary epidermoid cyst at the conus medullaris.
Case presentation
A 63-year-old Japanese woman working as a farmer presented with slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation erupted from the cystic lesion. We resected white cartilage-like pieces from the cystic cavity. Because the wall of the cystic lesion tightly adhered to the spinal cord parenchyma, we abandoned complete resection of the cyst wall. The pathological diagnosis was an epidermoid cyst.
Conclusions
We propose that evacuation of the cyst contents is preferable, especially in cases with elderly onset and congenital origin.
Electronic supplementary material
The online version of this article (doi:10.1186/1752-1947-9-7) contains supplementary material, which is available to authorized users.
doi:10.1186/1752-1947-9-7
PMCID: PMC4326493  PMID: 25582755
Epidermoid cyst; Intramedullary tumor; Conus medullaris
2.  Strategies for an effective tobacco harm reduction policy in Indonesia 
Epidemiology and Health  2014;36:e2014035.
Tobacco consumption is a major causative agent for various deadly diseases such as coronary artery disease and cancer. It is the largest avoidable health risk in the world, causing more problems than alcohol, drug use, high blood pressure, excess body weight or high cholesterol. As countries like Indonesia prepare to develop national policy guidelines for tobacco harm reduction, the scientific community can help by providing continuous ideas and a forum for sharing and distributing information, drafting guidelines, reviewing best practices, raising funds, and establishing partnerships. We propose several strategies for reducing tobacco consumption, including advertisement interference, cigarette pricing policy, adolescent smoking prevention policy, support for smoking cessation therapy, special informed consent for smokers, smoking prohibition in public spaces, career incentives, economic incentives, and advertisement incentives. We hope that these strategies would assist people to avoid starting smoking or in smoking cessation.
doi:10.4178/epih/e2014035
PMCID: PMC4322520  PMID: 25518881
Policy; Tobacco; Indonesia
3.  PainVision Apparatus Is Effective for Assessing Low Back Pain 
Asian Spine Journal  2014;8(6):793-798.
Study Design
Case series.
Purpose
To determine the utility of "PainVision" apparatus for the assessment of low back pain.
Overview of Literature
A newly developed device, the PainVision PS-2100 (Nipro, Osaka, Japan), has been used to assess the perception of pain in a quantitative manner. In the current study, we aimed to evaluate the efficacy of PainVision for the assessment of low back pain.
Methods
We assessed 89 patients with low back pain. The numeric rating scale (NRS) score, McGill Pain Questionnaire (MPQ) score and the degree of pain calculated by PainVision were measured twice at 4-week intervals in each patient. An electrode was patched on the forearm surface of the patients and the degree of pain was automatically calculated (degree of pain=100×[current producing pain comparable with low back pain-current at perception threshold/current at perception threshold]). Correlations between NRS and MPQ scores and the degree of pain were determined using Spearman's rank correlation test.
Results
There was a strong correlation between the NRS and MPQ scores at each time point (rs=0.60, p<0.0001). The degree of pain also showed a moderate correlation with NRS and MPQ scores at each time point (rs=0.40, p<0.03). The change in the degree of pain over 4 weeks showed a moderate correlation with changes in the NRS and MPQ scores (rs=0.40, p<0.01).
Conclusions
PainVision as self-reported questionnaires is a useful tool to assess low back pain.
doi:10.4184/asj.2014.8.6.793
PMCID: PMC4278985  PMID: 25558322
PainVision; Low back pain; Tool; Assessment
4.  Increase of TRPV1-Immunoreactivity in Dorsal Root Ganglia Neurons Innervating the Femur in a Rat Model of Osteoporosis 
Yonsei Medical Journal  2014;55(6):1600-1605.
Purpose
Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported.
Materials and Methods
TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating the femurs of Sprague Dawley rats were examined in control, sham, and ovariectomized (OVX) rats. We evaluated osteoporosis in the femurs and compared the proportion of TRPV1-ir DRG neurons innervating femur between the 3 groups of rats.
Results
OVX rats showed osteoporotic cancellous bone in the femur. FG labeled neurons were distributed from L1 to L6 DRG, but there was no significant difference in the proportion of labeled neurons between the 3 groups (p>0.05). The proportions of FG labeled TRPV1-ir DRG neurons were 1.7%, 1.7%, and 2.8% of DRG neurons innervating the femur, in control, sham-operated, and OVX rats, respectively. The proportion of TRPV1-ir neurons in DRG innervating the femur in OVX rats was significantly higher than that in control and sham-operated rats (p<0.05).
Conclusion
Under physiological conditions, DRG neurons innervating femurs in rats contain TRPV1. Osteoporosis increases the numbers of TRPV1-ir neurons in DRG innervating osteoporotic femurs in rats. These findings suggest that TRPV1 may have a role in sensory perception of osteoporotic femurs.
doi:10.3349/ymj.2014.55.6.1600
PMCID: PMC4205700  PMID: 25323897
Osteoporosis; pain; transient receptor potential vanilloid 1; femur
5.  Miniopen Oblique Lateral L5-S1 Interbody Fusion: A Report of 2 Cases 
Case Reports in Orthopedics  2014;2014:603531.
Extreme lateral interbody fusion (XLIF) has been widely used for minimally invasive anterior lumbar interbody fusion (ALIF), but an approach to L5-S1 is difficult because of the iliac crest. In the current study, we present 2 cases using minimally invasive oblique lateral interbody fusion (OLIF) of L5-S1. The patients showed foraminal stenosis between L5 and S1 and severe low back and leg pain. The patients were placed in a lateral decubitus position and underwent OLIF surgery (using a cage and bone graft from the iliac crest) without posterior decompression. Posterior screws were used in the patients. Pain scores significantly improved after surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. OLIF surgery was minimally invasive and produced good surgical results without complications.
doi:10.1155/2014/603531
PMCID: PMC4221972  PMID: 25400963
6.  Radiograms Obtained during Anterior Cervical Decompression and Fusion Can Mislead Surgeons into Performing Surgery at the Wrong Level 
Case Reports in Orthopedics  2014;2014:398457.
A 68-year-old woman who suffered from C5 nerve palsy because of a C4-5 disc herniation was referred to our hospital. We conducted anterior cervical decompression and fusion (ACDF) at the C4-5 level. An intraoperative radiogram obtained after exposure of the vertebrae showed that the level at which we were going to perform surgery was exactly at the C4-5 level. After bone grafting and temporary plating, another radiogram was obtained to verify the correct placement of the plate and screws, and it appeared to show that the plate bridged the C5 and C6 vertebrae at the incorrect level. The surgeon was astonished and was about to begin decompression of the upper level. However, carefully double-checking the level with a C-arm image intensifier before additional decompression verified that the surgery was conducted correctly at C4-5. Cautiously double-checking the level of surgery with a C-arm image intensifier is recommended when intraoperative radiograms suggest surgery at the wrong level.
doi:10.1155/2014/398457
PMCID: PMC4216671  PMID: 25386376
7.  Up-Regulation of Pain Behavior and Glial Activity in the Spinal Cord after Compression and Application of Nucleus Pulposus onto the Sciatic Nerve in Rats 
Asian Spine Journal  2014;8(5):549-556.
Study Design
Experimental animal study.
Purpose
To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats.
Overview of Literature
Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission.
Methods
The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively.
Results
Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05).
Conclusions
Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
doi:10.4184/asj.2014.8.5.549
PMCID: PMC4206803  PMID: 25346806
Rat; Pain; Nerve; Glia; Spinal cord
8.  Evaluation of Behavior and Expression of Receptor Activator of Nuclear Factor-Kappa B Ligand in Dorsal Root Ganglia after Sciatic Nerve Compression and Application of Nucleus Pulposus in Rats 
Asian Spine Journal  2014;8(5):557-564.
Study Design
Experimental animal study.
Purpose
To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats.
Overview of Literature
The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats.
Methods
Mechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry.
Results
Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01).
Conclusions
The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.
doi:10.4184/asj.2014.8.5.557
PMCID: PMC4206804  PMID: 25346807
Rat; Pain; Nerve; Receptor activator of nuclear factor-kappa B ligand; Nucleus pulposus
9.  Prevalence and risk factors of aortic aneurysm in patients with chronic obstructive pulmonary disease 
Journal of Thoracic Disease  2014;6(10):1388-1395.
Background
Patients with chronic obstructive pulmonary disease (COPD) manifest an excess of chronic co-morbidities and present a high prevalence of cardiovascular disease such as congestive heart failure and ischemic heart disease. Aortic aneurysm (AA) also shared the risks of those diseases and its rupture is an important cause of death. However, since AA progresses almost silently, the prevalence of AA in patients with COPD remains unclear. The aim of this study was to determine AA prevalence and risk factors in patients with COPD.
Methods
With computed tomography (CT) screening, we tested for AA in 231 COPD patients, and assessed emphysema by Goddard classification and aortic wall calcification in abdominal artery, respectively. We also evaluated that of thoracic artery using our original methods, which we assessed the extent of calcification in the thoracic artery as well as which defined as “aortic calcification index (ACI) in thoracic artery”.
Results
In 231 patients with COPD, 27 (11.7%) had AA determined by CT imaging and another 6 patients with previously diagnosed AA and a history of repaired operation (2.6%). In this total of 33 patients (AA group), the age of 95% confidence interval (CI) was 75.8 to 80.1 years and the prevalence of AA in patients aged 76 to 80 years was 26.8%. A low attenuation area and aortic wall calcification were more severe in the AA group than in the non-AA group, but forced expiratory volume in 1 second (FEV1) was not significantly different in those patients. The Goddard score of nine and ACI in the thoracic artery of 25.0% were determined to identify the most appropriate cut-off levels for discriminating between AA and non-AA groups.
Conclusions
Our analysis indicated that sizeable under-recognition of AA seems likely in COPD. Especially for patients with severe lung destruction and aortic calcification verifiable by chest CT, abdominal CT would be beneficial for detecting AA.
doi:10.3978/j.issn.2072-1439.2014.10.01
PMCID: PMC4215129  PMID: 25364515
Aortic aneurysm (AA); calcification; chronic obstructive pulmonary disease (COPD); co-morbidity; computed tomography (CT)
10.  Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma 
Cancer Medicine  2014;3(5):1377-1384.
Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7–16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7–20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7–20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7–20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7–20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma.
doi:10.1002/cam4.297
PMCID: PMC4302688  PMID: 25045139
Area under the curve; biomarker; ELISA; N-ERC/mesothelin; pleural mesothelioma
11.  Lateral insertion is a good prognostic factor after in situ fixation in slipped capital femoral epiphysis 
Background
In situ fixation (ISF) is standard treatment for slipped capital femoral epiphysis (SCFE) to stabilize the epiphysis and to prevent further slip. The aim of this study was to clarify the incidence of slip progression after ISF and its prognostic factors.
Methods
We retrospectively reviewed 53 hips in 49 consecutive SCFE patients who underwent single screw ISF and were followed until physeal closure. Clinical and radiographic findings were viewed to assess progression of the posterior tilting angle (PTA).
Results
Mean PTA was 33.4 degrees (range, 18 to 75 degrees) at ISF and 35.9 degrees (range, 18 to 75 degrees) at physeal closure with progression of PTA of 2.5 degrees (range, -2 to 19 degrees). Slip progression occurred in 28 of 53 hips (53%), and more than five degrees of progression occurred in 14 hips (26%). Multiple regression analysis revealed that point of screw insertion (one point for lateral and two points for medial) was a significant prognostic factor for progression of the slip by the following formula: (progression of PTA) = -1.523 + 2.701 × (point of screw insertion), R2 = 0.148, p = 0.005.
Conclusions
The current study showed that a screw inserted from the lateral side to the intertrochanteric line prevented postoperative slip progression.
doi:10.1186/1471-2474-15-317
PMCID: PMC4189656  PMID: 25260766
12.  Year in review 2013: Lung cancer, respiratory infections, tuberculosis, cystic fibrosis, pleural diseases, bronchoscopic intervention and imaging 
Respirology (Carlton, Vic.)  2014;19(3):448-460.
doi:10.1111/resp.12250
PMCID: PMC4151183  PMID: 24708034
bronchoscopic intervention and imaging; cystic fibrosis; lung cancer; pleural disease; respiratory infection; tuberculosis
13.  Progressive Change in Joint Degeneration in Patients with Knee or Hip Osteoarthritis Treated with Fentanyl in a Randomized Trial 
Yonsei Medical Journal  2014;55(5):1379-1385.
Purpose
Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids.
Materials and Methods
Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated.
Results
Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group.
Conclusion
Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
doi:10.3349/ymj.2014.55.5.1379
PMCID: PMC4108827  PMID: 25048500
Opioid; knee; hip; osteoarthritis
14.  Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis 
BMJ Open  2014;4(8):e005615.
Objectives
Biological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD.
Design
Case–control cohorts.
Setting
Single centre in Japan.
Participants
This study included 163 patients with RA who underwent biological therapy.
Outcome measured
We assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an ‘ILD event’. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics.
Results
Tumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events.
Conclusions
TNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients.
doi:10.1136/bmjopen-2014-005615
PMCID: PMC4139628  PMID: 25125479
Tumor necrosis factor inhibitors; Rheumatoid arthritis
15.  Additional decompression at adjacent segments leads to adjacent segment degeneration after PLIF 
European Spine Journal  2013;22(8):1877-1883.
Purpose
Adjacent segment degeneration (ASD) is one of the major complications of lumbar fusion. Several previous retrospective studies reported ASD after PLIF. However, few reports evaluated whether decompression surgery combined with fusion surgery increases the rate of complications in adjacent segments. The purpose of the current study was to investigate the degeneration in decompressed adjacent segments after PLIF.
Methods
A total of 23 patients (12 men, 11 women; average age, 58.6) who underwent PLIF surgery [1 level (n = 9), 2 levels (n = 8), 3 levels (n = 4), 4 levels (n = 2)] were included. Additional adjacent decompression above or below the level of interbody fusion was performed at 25 levels and no adjacent decompression was performed at 15 levels. We retrospectively investigated ASD by X-ray films of all 40 adjacent segments (above and below fusion level) and clinical outcomes of all 23 cases.
Results
Of the 40 adjacent segments, 19 (47.5 %) showed ASD and 9 (22.5 %) showed symptomatic ASD. In the 19 segments with ASD, ASD occurred in 16 of 25 (64.0 %) segments at decompressed sites compared with 3 of 15 (20.0 %) non-decompressed sites. The ratio of ASD in adjacent segments was significantly higher at decompressed sites than at non-decompressed sites (p < 0.01).
Conclusion
ASD occurs frequently in association with additional decompression above or below the level of PLIF. In cases in which the adjacent segments require decompression, a surgical strategy that preserves as much of the posterior complex as possible should be selected.
doi:10.1007/s00586-013-2694-8
PMCID: PMC3731485  PMID: 23404354
Adjacent segment degeneration (ASD); Posterior lumbar interbody fusion (PLIF); Decompression surgery; Spinal canal stenosis
16.  Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats 
European Spine Journal  2013;22(8):1794-1799.
Purpose
Clinically, neuropathic pain is frequent and intense following brachial plexus injury. It is thought that brachial plexus pain is not generated by avulsed roots, but rather by non-avulsed roots, since the avulsed root could not possibly transmit action potentials to central nerves. The aim of this study was to evaluate pain behavior and activation of sensory neurons in a brachial plexus avulsion (BPA) model in rats.
Methods
Fifteen male Wistar rats were used. In the BPA group, the C8–T1 roots were avulsed from the spinal cord with forceps at the lower trunk level (n = 5). In the naïve group, rats did not receive any procedures (n = 5). In the sham-operated group, the lower trunk was simply exposed (n = 5). Mechanical hyperalgesia of forelimbs corresponding to C6 and C7 dermatomes was measured using von Frey filaments every third day for 3 weeks. Activation of DRG neurons was immunohistochemically examined using anti-ATF3 (a marker for neuron activation) antibodies 21 days after surgery. Von Frey and immunohistochemical data between groups were analyzed using a Kruskal–Wallis test, followed by Mann–Whitney U tests. Bonferroni corrections were performed.
Results
Animals in the BPA group displayed significant mechanical hyperalgesia at the dermatome innervated by uninjured nerves continuing through day 21 compared with animals in the sham-operated group. ATF3-immunoreactive small and large DRG neurons were significantly activated in the BPA group (10.6 ± 9.5 and 5.2 ± 4.1 %, 39.7 ± 6.7 and 25.2 ± 10.3 %, 78.0 ± 9.1 and 53.7 ± 29.3 %) compared with the sham-operated group (0.7 ± 0.9 and 0 ± 0 %, 2.8 ± 2.0 and 1.0 ± 2.0 %, 3.9 ± 2.7 and 8.6 ± 10.1 %) at every level of C5, 6, and 7. In the naïve group, no DRG neurons were activated. ATF3-immunoreactive small and large DRG neurons were significantly activated at the level of C7 compared with C6 and C5, and significantly activated at the level of C6 compared with C5 in the BPA group.
Conclusions
Expression of ATF3 in uninjured DRG neurons may contribute to pain following brachial plexus avulsion injury. Consequently, spared spinal sensory nerves may represent therapeutic targets for treatment of this pain.
doi:10.1007/s00586-013-2733-5
PMCID: PMC3731502  PMID: 23471575
Brachial plexus avulsion; Pain; ATF3; Immunohistochemistry; Rat model
17.  Increase of nerve growth factor levels in the human herniated intervertebral disc: can annular rupture trigger discogenic back pain? 
Arthritis Research & Therapy  2014;16(4):R159.
Introduction
Nerve growth factor (NGF) has an important role in the generation of discogenic pain. We hypothesized that annular rupture is a trigger for discogenic pain through the action of NGF. In this study, the protein levels of NGF in discs from patients with disc herniation were examined and compared with those from discs of patients with other lumbar degenerative disc diseases.
Methods
Patients (n = 55) with lumbar degenerative disc disease treated by surgery were included. Nucleus pulposus tissue (or herniated disc tissue) was surgically removed and homogenized; protein levels were quantified using an enzyme-linked immunosorbent assay (ELISA) for NGF. Levels of NGF in the discs were compared between 1) patients with herniated discs (herniated group) and those with other lumbar degenerative disc diseases (non-herniated group), and 2) low-grade and high-grade degenerated discs. Patient’s symptoms were assessed using a visual analog scale (VAS) and the Oswestry disability index (ODI); the influence of NGF levels on pre- and post-operative symptoms was examined.
Results
Mean levels of NGF in discs of patients were significantly higher in herniated discs (83.4 pg/mg total protein) than those in non-herniated discs (68.4 pg/mg).
No significant differences in levels of NGF were found between low-grade and high-grade degenerated discs. Multivariate analysis, adjusted for age and sex, also showed significant correlation between the presence of disc herniation and NGF levels, though no significant correlation was found between disc degeneration and NGF levels. In both herniated and non-herniated groups, pre-operative symptoms were not related to NGF levels. In the herniated group, post-operative lower extremity pain and low back pain (LBP) in motion were greater in patients with low levels of NGF; no significant differences were found in the non-herniated group.
Conclusions
This study reports that NGF increased in herniated discs, and may play an important role in the generation of discogenic pain. Analysis of patient symptoms revealed that pre-operative NGF levels were related to post-operative residual lower extremity pain and LBP in motion. The results suggest that NGF in the disc is related to pain generation, however, the impact of NGF on generation of LBP varies in individual patients.
Electronic supplementary material
The online version of this article (doi:10.1186/ar4674) contains supplementary material, which is available to authorized users.
doi:10.1186/ar4674
PMCID: PMC4261264  PMID: 25069717
18.  Tocilizumab, a Proposed Therapy for the Cachexia of Interleukin6-Expressing Lung Cancer 
PLoS ONE  2014;9(7):e102436.
Background
We previously reported the role of IL-6 in a murine model of cancer cachexia and currently documented a patient in whom tocilizumab, anti-IL-6 receptor antibody, dramatically improved cachexia induced by IL-6 over-expressing lung cancer. Despite this potential to alleviate cancer cachexia, tocilizumab has not been approved for this clinical use. Therefore, preceding our planned clinical trial of tocilizumab, we designed the two studies described here to evaluate the levels of IL-6 in patients with lung cancer and the effect of tocilizumab in a murine model of human cancer cachexia.
Methods
First, we measured serum IL-6 levels in patients with lung cancer and analyzed its association with cachexia and survival. Next, we examined the effect of a rodent analog of tocilizumab (MR16-1) in the experimental cachexia model.
Results
Serum IL-6 levels were higher in patients with cachexia than those without cachexia. In patients with chemotherapy-resistant lung cancer, a high IL-6 serum level correlated strongly with survival, and the cut-off level for affecting their prognosis was 21 pg/mL. Meanwhile, transplantation of IL-6-expressing Lewis Lung Carcinoma cells caused cachexia in mice, which then received either MR16-1 or 0.9% saline. Tumor growth was similar in both groups; however, the MR16-1 group lost less weight, maintained better food and water intake and had milder cachectic features in blood. MR16-1 also prolonged the survival of LLC-IL6 transplanted mice (36.6 vs. 28.5 days, p = 0.016).
Conclusion
Our clinical and experimental studies revealed that serum IL-6 is a surrogate marker for evaluating cachexia and the prognosis of patients with chemotherapy resistant metastatic lung cancer and that tocilizumab has the potential of improving prognosis and ameliorating the cachexia that so devastates their quality of life. This outcome greatly encourages our clinical trials to evaluate the safety and efficacy of tocilizumab treatment for patients with increased serum IL-6.
doi:10.1371/journal.pone.0102436
PMCID: PMC4092149  PMID: 25010770
19.  Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease 
BMC Cancer  2014;14:508.
Background
Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established.
Method
We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed.
Results
Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity.
Conclusion
We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs.
doi:10.1186/1471-2407-14-508
PMCID: PMC4107964  PMID: 25012241
Non-small cell lung cancer; Pemetrexed; Interstitial pneumonitis; Idiopathic pulmonary fibrosis; Acute lung injury; Acute exacerbation
20.  Postoperative Improvement of Femoroacetabular Impingement After Intertrochanteric Flexion Osteotomy for SCFE 
Background
Patients with slipped capital femoral epiphysis (SCFE) may develop cam-type femoroacetabular impingement (FAI). Early management of FAI has been advocated for patients with symptomatic FAI. The various treatment options, including reorientation surgeries, realignment procedures, and osteoplasty, remain controversial.
Questions/purposes
We asked whether an intertrochanteric flexion osteotomy improved the clinical symptoms of FAI in patients with SCFE and confirmed whether the radiographic signs were compatible with the clinical signs of FAI.
Methods
We retrospectively reviewed 32 symptomatic patients who underwent 32 intertrochanteric flexion osteotomies for severe SCFE. FAI was diagnosed clinically with a positive impingement sign. The osteotomies were designed preoperatively using CT. Cam-type FAI was evaluated with the modified α angle (β angle) on a Lauenstein view, measured between the proximal femoral shaft axis and the line from the center of the femoral head to the anterior point where the distance of the head center exceeded the femoral head radius. The minimum followup was 2 years (mean, 5 years; range, 2–9 years).
Results
At last followup, only two patients complained of pain or inconvenience in daily life; the impingement sign was negative in 24 hips (75%). The β angles at last followup were reduced on average by 39°. The postoperative β angle was higher in hips with positive clinical signs of FAI than in those with negative signs.
Conclusions
Intertrochanteric flexion osteotomy for SCFE improved the clinical and radiographic signs of FAI. The β angle and clinical findings showed compatible improvement. We believe our intertrochanteric flexion osteotomy is a viable option for treating severe SCFE.
Level of Evidence
Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-013-2817-x
PMCID: PMC3676605  PMID: 23397313
21.  Interspinous Ligament Lidocaine and Steroid Injections for the Management of Baastrup's Disease: A Case Series 
Asian Spine Journal  2014;8(3):260-266.
Study Design
Prospective study.
Purpose
To examine the long-term effects of interspinous ligament injections of local anesthetics and steroids for the treatment of Baastrup's diseases.
Overview of Literature
Baastrup's disease is associated with axial low back pains. Baastrup's disease has been more recently described as the "kissing spinous processes" disease. Several authors have reported methods for the diagnosis and treatment of the disease. However, there has been only one report of patients receiving interspinous ligament injections of agents for the treatment of Baastrup's disease.
Methods
Seventeen patients showed severe low back pains between spinous processes at L3-L4 or L4-L5. X-ray imaging, computed tomography, and magnetic resonance imaging revealed kissing spinous processes, consolidation of spinous process, or inflammation of an interspinous ligament. Pain reliefs after lidocaine and dexamethasone administration into interspinous ligament as therapy for low back pains were being examined and followed up.
Results
Low back pain scores significantly improved immediately after injection of the agents into interspinous ligaments. At final follow-up (1.4 year), low back pain scores significantly improved as compared with before the treatment.
Conclusions
Findings from the current study indicate that lidocaine and dexamethasone administration into interspinous ligament in patients diagnosed with Baastrup's disease is effective for managing the pain associated with this disease.
doi:10.4184/asj.2014.8.3.260
PMCID: PMC4068845  PMID: 24967039
Pain; Local anesthetic; Steroid
22.  L5 spinal nerve injury caused by misplacement of outwardly-inserted S1 pedicle screws 
European Spine Journal  2012;22(Suppl 3):461-465.
Purpose
To evaluate L5 nerve root injuries caused by outwardly misplaced S1 pedicle screws.
Summary of Background Data
Pedicle screws remain the criterion standard for fixation of L5–S1 to correct lumbosacral instability. When inserting S1 pedicle screws, it is possible to injure the L5 nerve root if screws are inserted outwardly and the tip of the screw perforates the anterior cortex of the sacrum. Despite this risk, to our knowledge this type of injury has never been reported as a case series.
Methods
We experienced 2 cases of L5 nerve root injury caused by outwardly-inserted S1 pedicle screws. In both cases, bilateral S1 pedicle screws were inserted outwardly using a free-hand technique, and on one side, screws induced severe pain by impinging on an L5 root. Computed tomography after the selective rootgraphy of the injured nerve showed the nerve compressed laterally by screw threads in Case 1 and crushed between the screw threads and the sacral body in Case 2.
Results
In both cases, leg pain disappeared immediately after the infiltration of the nerve with lidocaine, but symptoms recurred within a few days in Case 1 and within an hour in Case 2. Conservative treatment of three spinal nerve infiltrations was effective in Case 1, but reinsertion of the rogue screw was necessary in Case 2.
Conclusions
Surgeons should recognize that lateral inclination of S1 pedicle screws can cause L5 nerve root injury, which may require reinsertion of the screw, especially in cases where insertion is difficult because of overlapping surrounding muscle or bony tissue.
doi:10.1007/s00586-012-2634-z
PMCID: PMC3641263  PMID: 23269529
Nerve injury; Pedicle screw; Lumbosacral fixation
23.  Incidence of Nocturnal Leg Cramps in Patients with Lumbar Spinal Stenosis before and after Conservative and Surgical Treatment 
Yonsei Medical Journal  2014;55(3):779-784.
Purpose
To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS.
Materials and Methods
The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment.
Results
The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122).
Conclusion
The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.
doi:10.3349/ymj.2014.55.3.779
PMCID: PMC3990082  PMID: 24719148
Nocturnal leg cramps; pain; lumbar spinal stenosis; surgery; decompression; fusion; conservative treatment; severity; prospective study; outcome; comparison
24.  Year in review 2012: Lung cancer, respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging 
Respirology (Carlton, Vic.)  2013;18(3):573-583.
doi:10.1111/resp.12048
PMCID: PMC3606639  PMID: 23317457
lung cancer; respiratory infections; tuberculosis; pleural diseases; bronchoscopic intervention and imaging
25.  Treatment with basic fibroblast growth factor-incorporated gelatin hydrogel does not exacerbate mechanical allodynia after spinal cord contusion injury in rats 
Besides stimulating angiogenesis or cell survival, basic fibroblast growth factor (bFGF) has the potential for protecting neurons in the injured spinal cord.
Objective
To investigate the effects of a sustained-release system of bFGF from gelatin hydrogel (GH) in a rat spinal cord contusion model.
Methods
Adult female Sprague–Dawley rats were subjected to a spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 kdyn). One week after contusion, GH containing bFGF (20 µg) was injected into the lesion epicenter (bFGF – GH group). The GH-only group was designated as the control. Locomotor recovery was assessed over 9 weeks by Basso, Beattie, Bresnahan rating scale, along with inclined plane and Rota-rod testing. Sensory abnormalities in the hind paws of all the rats were evaluated at 5, 7, and 9 weeks.
Results
There were no significant differences in any of the motor assessments at any time point between the bFGF – GH group and the control GH group. The control GH group showed significantly more mechanical allodynia than did the group prior to injury. In contrast, the bFGF – GH group showed no statistically significant changes of mechanical withdrawal thresholds compared with pre-injury.
Conclusion
Our findings suggest that bFGF-incorporated GH could have therapeutic potential for alleviating mechanical allodynia following spinal cord injury.
doi:10.1179/2045772312Y.0000000030
PMCID: PMC3595961  PMID: 23809528
Allodynia; Basic fibroblast growth factor; Scaffold; Spinal cord injuries; Motor deficits; Neuroprotection; Locomotor recovery; Paraplegia

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