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1.  High sensitive C-reactive protein-Effective tool in determining postoperative recovery in lumbar disc disease 
Indian Journal of Orthopaedics  2014;48(4):354-359.
Background:
It is common in medical practice to see patients having persistent pain and radiculopathy even after undergoing discectomy surgery. Inflammatory cytokines, such as interleukins are produced at the site of disc herniation and are now considered responsible for the pain perceived by the patient. This study has used high sensitive C-reactive protein (HSCRP) assay for predicting inflammation around the nerve roots on very same principle, which has used HSCRP for predicting coronary artery diseases in current clinical practice. Thus, purpose of this study is to test whether HSCRP can stand as an objective tool to predict postoperative recovery in patients undergoing lumbar discectomy. That is, to study association between preoperative HSCRP blood level and postoperative recovery with the help of modified Oswestry Back Disability Score.
Materials and Methods:
A study group consisting of 50 cases of established lumbar disc disease and control group of 50 normal subjects, matched with the study group. Both the study and control groups were subjected to detailed evaluation with the help of modified Oswestry Low Back Pain Scale both pre and postoperatively at 3 months, 6 months and 1-year. The preoperative blood samples were analyzed to assess the HSCRP concentration. All the cases underwent surgery over a period of 1-year by the same surgeon.
Results:
The level of HSCRP in the study group was between 0.050– and 0.710 mg/dL and in the control group, 0.005-0.020 mg/dL. There was highly significant positive correlation between preoperative HSCRP level and postoperative score at P < 0.005. Cases with HSCRP level in the range of 0.1820 ± 0.079 mg/dL, showed better recovery (score improved > 10 points), while those with HSCRP level in the range of 0.470 ± 0.163 mg/dL, showed poor recovery (score improved < 10 points).
Conclusion:
HSCRP will serve as a good supplementary prognostic marker for operative decision making in borderline and troublesome cases of lumbar disc disease.
doi:10.4103/0019-5413.136216
PMCID: PMC4137511  PMID: 25143637
Lumbar disc disease; sciatica; discectomy; high sensitive C-reactive protein; Lumbar; disc; herniated; sciatica; blood proteins
2.  Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain 
Annals of the Rheumatic Diseases  2005;64(6):921-925.
Background: The severity of pain from musculoskeletal disorders might be associated with high sensitivity C reactive protein (hsCRP), a sensitive marker of low grade systemic inflammation.
Objective: To study the association between pain as assessed by a visual analogue scale (VAS) and hsCRP in patients with chronic low back pain and acute sciatic pain.
Methods: Information on pain severity, determinants of hsCRP, and hsCRP values were obtained prospectively at up to 10 time points during six months in 72 consecutive patients (mean age 43.3 years; 59.7% female): 41 with chronic low back pain and 31 with acute sciatic pain. The association between severity of pain and raised (highest quartile) hsCRP values at any time point was estimated by multivariable logistic regression using generalised estimating equations to adjust odds ratios (OR) and their confidence intervals (CI) for intraindividual dependence of measurements.
Results: Mean intensity of pain (VAS 0–10) at baseline was 4.9 and 5.5 in patients with chronic low back and acute sciatic pain, respectively. Highest v lowest tertile of average intensity of pain during the last 24 hours was associated with increased hsCRP levels among patients with acute sciatic pain (adjusted OR = 3.4 (95% CI, 1.1 to 10), but not in patients with chronic low back pain (adjusted OR = 0.87 (0.25 to 3.0)).
Conclusions: Mean intensity of pain during the previous 24 hours as assessed by VAS was independently associated with high levels of hsCRP in patients with acute sciatic pain but not in those with chronic low back pain.
doi:10.1136/ard.2004.027045
PMCID: PMC1755532  PMID: 15897311
3.  Isolated septic facet joint arthritis as a rare cause of acute and chronic low back pain – a case report and literature review 
Polish Journal of Radiology  2012;77(4):72-76.
Summary
Background:
The most common cause of low back pain is degenerative disease of the intervertebral disc and other structures of the lumbar spine. However, in some cases other less frequent causes of such pain can be seen, for example septic facet joint arthritis. Until now, only 40 cases of such inflammatory changes within the spine have been reported in the literature. The disease is probably underestimated due to improper diagnostic pathway.
Case Report:
The authors describe a case of a 53-year-old woman who was repeatedly hospitalized during a five-month period because of an acute, severe low back pain, with sphincter dysfunction, partially resembling sciatic symptoms. Physical examinations revealed also focal tenderness in the area of the lumbar spine. Inflammatory markers (ESR – erythrocyte sedimentation rate, CRP – C-reactive protein) were elevated. Conservative analgetic treatment brought only partial and temporary relief of the pain and symptoms. The final accurate diagnosis of isolated septic facet joint arthritis at the level of L5/S1 was established after several months from the onset of the first symptoms, after performing various imaging examinations, including bone scintigraphy as well as CT and MRI of the lumbosacral spine. The patient fully recovered after antibiotic therapy and surgery, which was proven in several follow-up examinations showing no relevant pathology of the lumbar spine. The authors broadly describe the etiology and clinical symptoms of the septic facet joint arthritis as well as the significant role of imaging methods, especially MRI, in diagnostic process. The authors also discuss currently available treatment options, both conservative and surgical.
Conclusions:
The diagnostic procedure of septic facet joint arthritis requires several steps to be taken. Establishing a correct diagnosis may be difficult, that is why it is important to remember about rare causes of low back pain and to perform detailed physical examination, laboratory tests and choose appropriate imaging techniques.
PMCID: PMC3529718  PMID: 23269942
low back pain; diagnostics; facet joint arthritis
4.  A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation 
PLoS Medicine  2010;7(9):e1000341.
A genetic association study by Timothy Vyse and colleagues suggests that there is a significant association between CRP variants and acute-phase serum CRP concentrations in patients with rheumatoid arthritis, including those with chronic inflammation.
Background
The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation.
Methods and Findings
We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, p<0.0005, p<0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR = 50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1–50.0) for haplotype 1 and 14.2 mg/l (9.5–23.2) for haplotype 4.
Conclusions
Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP–associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.
Please see later in the article for the Editors' Summary
Editors' Summary
C-reactive protein (CRP) is a serum marker for inflammation or infection and acts by binding to a chemical (phosphocholine) found on the surface of dead or dying cells (and some types of bacteria) in order to activate the immune system (via the complement system). Fat cells release factors that stimulate the liver to produce CRP, and serum levels greater than 10 mg/l are generally considered indicative of an infectious or inflammatory process. After an inflammatory stimulus, serum CRP levels may exceed 500 times baseline, so CRP is used in all medical specialities to help diagnose inflammation and infection. Although patients with chronic inflammatory diseases, such as rheumatoid arthritis, have raised levels of CRP, levels of CRP are still highly variable. Some studies have suggested that there may be genetic variations of CRP (CRP variants) that determine the magnitude of the acute-phase CRP response, a finding that has important clinical implications: CRP thresholds are used as a diagnostic component of formal clinical algorithms and play an important role in a clinician's decision-making process when diagnosing inflammatory disease and choosing treatment options. Therefore, it is possible that false reassurance could be given to a patient with disease, or optimal treatment withheld, because some patients are genetically predisposed to have only a modest increase in acute-phase CRP.
Why Was This Study Done?
Although some studies have looked at the CRP gene variant response, few, if any, studies have examined the CRP gene variant response in the context of chronic inflammation, such as in rheumatoid arthritis. Therefore, this study aimed to determine whether CRP gene variants could also influence CRP serum levels in rheumatoid arthritis.
What Did the Researchers Do and Find?
The authors studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients): one patient set used a cohort of 281 patients in the UK, and the other patient set (used for replication) consisted of 414 patients from New Zealand and Australia. A genetic technique (a tagSNP approach) was used to capture common variations at the CRP locus (haplotype association analysis) at both the population and the individual level. The relationship between genotype and serum CRP was explored by linear modeling. The researchers found that common genetic variants at the CRP locus were associated with acute-phase serum CRP in both patient sets translating into an approximate 3.5-fold change in expected serum CRP between carriers of two common CRP variants. For example, when ESR = 50 mm/h the expected CRP serum level for one common CRP variant was 43.1 mg/l and for another CRP variant was 14.2 mg/l.
What Do These Findings Mean?
The findings of this study raise questions about the interpretation of acute-phase serum CRP, as they suggest that there is a significant association between CRP variants and acute-phase serum CRP concentrations in a group of patients with rheumatoid arthritis, including those with chronic active inflammation. The size of the genetic effect may be large enough to have a clinically relevant impact on the assessment of inflammatory disease activity, which in turn may influence therapeutic decision making. Failure to take into account the potential for genetic effects may result in the inappropriate reassurance or undertreatment of patients simply because they carry low-CRP–associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events, so these findings impact on the use of such algorithms. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000341
Lab Test Online provides information on CRP
The Wellcome Trust provides a glossary of genetic terms
Learn.Genetics provides access to the Genetic Science Learning Center, which is part of the human genome project
doi:10.1371/journal.pmed.1000341
PMCID: PMC2943443  PMID: 20877716
5.  Analysis of Efficacy Differences between Caudal and Lumbar Interlaminar Epidural Injections in Chronic Lumbar Axial Discogenic Pain: Local Anesthetic Alone vs. Local Combined with Steroids 
Study Design: Comparative assessment of randomized controlled trials of caudal and lumbar interlaminar epidural injections in chronic lumbar discogenic pain.
Objective: To assess the comparative efficacy of caudal and lumbar interlaminar approaches of epidural injections in managing axial or discogenic low back pain.
Summary of Background Data: Epidural injections are commonly performed utilizing either a caudal or lumbar interlaminar approach to treat chronic lumbar axial or discogenic pain, which is pain exclusive of that associated with a herniated intervertebral disc, or that is due to degeneration of the zygapophyseal joints, or due to dysfunction of the sacroiliac joints, respectively. The literature on the efficacy of epidural injections in managing chronic axial lumbar pain of presumed discogenic origin is limited.
Methods: The present analysis is based on 2 randomized controlled trials of chronic axial low back pain not caused by disc herniation, radiculitis, or facet joint pain, utilizing either a caudal or lumbar interlaminar approach, with a total of 240 patients studied, and a 24-month follow-up. Patients were assigned to receive either local anesthetic only or local anesthetic with a steroid in each 60 patient group.
Results: The primary outcome measure was significant improvement, defined as pain relief and functional status improvement of at least 50% from baseline, which was reported at 24-month follow-ups in 72% who received local anesthetic only with a lumbar interlaminar approach and 54% who received local anesthetic only with a caudal approach. In patients receiving local anesthetic with a steroid, the response rate was 67% for those who had a lumbar interlaminar approach and 68% for those who had a caudal approach at 12 months. The response was significantly better in the lumbar interlaminar group who received local anesthetic only, 77% versus 56% at 12 months and 72% versus 54% at 24 months.
Conclusion: This assessment shows that in patients with axial or discogenic pain in the lumbar spine after excluding facet joint and SI Joint pain, epidural injections of local anesthetic by the caudal or lumbar interlaminar approach may be effective in managing chronic low back pain with a potential superiority for a lumbar interlaminar approach over a caudal approach.
doi:10.7150/ijms.10870
PMCID: PMC4323359
Chronic low back pain; axial low back pain; lumbar discogenic pain; caudal epidural injections; lumbar interlaminar epidural injections.
6.  Hormonal and Nutritional Effects on Cardiovascular Risk Markers in Young Women 
Context
Cardiovascular (CV) risk markers, including high-sensitivity C-reactive protein (hsCRP), are increasingly important in predicting cardiac events. A favorable CV risk profile might be expected in anorexia nervosa (AN) due to low body weight and dietary fat intake. However, women with AN have decreased IGF-I levels reflecting decreased GH action, and IGF-I deficiency is associated with elevated hsCRP. Moreover, oral estrogens, known to increase hsCRP in other populations, are commonly prescribed in AN. To date, hsCRP levels and their physiological determinants have not been reported in women with AN.
Objective
We examined the relationship between CV risk markers, undernutrition, IGF-I, and oral estrogens, specifically hypothesizing that in the setting of undernutrition, AN would be associated with low hsCRP despite low IGF-I levels and that those women taking oral contraceptive pills (OCPs) would have higher hsCRP and lower IGF-I levels.
Design and Setting
We conducted a cross-sectional study at a clinical research center.
Study Participants
Subjects included 181 women: 140 women with AN [85 not receiving OCPs (AN-E) and 55 receiving OCPs (AN+E)] and 41 healthy controls [28 not receiving OCPs (HC-E) and 13 receiving OCPs (HC+E)].
Main Outcome Measures
We assessed hsCRP, IL-6, IGF-I, low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
Results
Despite low weight, more than 20% of AN+E had high-risk hsCRP levels. AN+E had higher hsCRP than AN-E. AN-E had lower mean hsCRP levels than healthy controls (HC+E and HC-E). IL-6 levels were higher in AN+E with elevated hsCRP (>3 mg/liter) than in AN+E with normal hsCRP levels. IGF-I was inversely associated with hsCRP in healthy women, suggesting a protective effect of GH on CV risk. However, this was not seen in AN. Few patients in any group had high-risk LDL or HDL levels.
Conclusions
Although hsCRP levels are lower in AN than healthy controls, OCP use puts such women at a greater than 20% chance of having hsCRP in the high-CV-risk (>3 mg/liter) category. The elevated mean IL-6 in women with AN and high-risk hsCRP levels suggests that increased systemic inflammation may underlie the hsCRP elevation in these patients. Although OCP use in AN was associated with slightly lower mean LDL and higher mean HDL, means were within the normal range, and few patients in any group had high-risk LDL or HDL levels. IGF-I levels appear to be important determinants of hsCRP in healthy young women. In contrast, IGF-I does not appear to mediate hsCRP levels in AN.
doi:10.1210/jc.2007-0364
PMCID: PMC3211045  PMID: 17519306
7.  Lumbar Periradicular Abscess Mimicking a Fragmented Lumbar Disc Herniation : An Unusual Case 
We herein describe the case of a focal spontaneous spinal epidural abscess who was initially diagnosed to have a free fragment of a lumbar disc. A 71-year-old woman presented with history of low back and right leg pain. Magnetic resonance imaging suggested a peripherally enhancing free fragment extending down from S1 nerve root axilla. Preoperative laboratory investigation showed elevation of c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels. She was taken for surgery and a fluctuating mass at the axilla of S1 nerve was found. When the mass was probed with a dissector, a dark yellow, thick pus drained out. Pus cultures were negative. Patients who present with extreme low back plus leg pain and increased leucocyte count, ESR and CRP levels should raise the suspicion of an infection of a vertebral body or spinal epidural space.
doi:10.3340/jkns.2008.44.6.385
PMCID: PMC2615143  PMID: 19137084
Abscess; Disc; Periradicular; Spinal
8.  High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy 
Open Heart  2015;2(1):e000152.
Aims
To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS).
Methods and results
In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92) mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35) mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1 year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP.
Conclusions
The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP.
Trial registration
NCT00092677.
doi:10.1136/openhrt-2014-000152
PMCID: PMC4322313
9.  Salt Intake Is Associated with Inflammation in Chronic Heart Failure 
Background:
Chronic Heart Failure (CHF) is highly prevalent and is associated with high morbidity and mortality rates. It has been well established that excessive intake of sodium chloride (salt) induced hypertension in some populations. Although salt seems to induce cardiovascular diseases through elevation of blood pressure, it has also been indicated that salt can induce cardiovascular diseases independently from blood pressure elevation.
Objectives:
The present study aimed to evaluate the association between salt consumption and inflammation in CHF patients.
Patients and Methods:
This study was conducted on 86 patients between 18 and 65 years old who were diagnosed with New York Heart Association (NYHA) functional class I and II heart failure. Salt intake was calculated by using 24 hour urine sodium excretion. Besides, the association between inflammation and daily salt intake was evaluated regarding C - reactive protein (CPR), High sensitive CRP (HsCPR), Erythrocyte Sedimentation Rate (ESR), and ferritin and fibrinogen levels using Pearson correlation analysis.
Results:
Our results showed a statistically significant difference between the low (n = 41) and high (n = 45) salt intake groups in terms of serum HsCRP levels (5.21 ± 2.62 vs. 6.36 ± 2.64) (P < 0.048). Additionally, a significant correlation was observed between the amount of salt consumption and HsCRP levels. In this study, daily salt consumption of the enrolled patients was 8.53 gram/day. The medications and even the blood pressures were similar in the two groups, but daily pill count, prevalence of hypertension, and coronary heart disease were higher in the high salt intake group; however, the differences were not statistically significant (P = 0.065). Also, no significant difference was observed between the groups concerning the inflammation markers, such as CRP, ESR, ferritin, and fibrinogen.
Conclusions:
Neurohumoral and inflammatory factors are thought to contribute to high mortality and morbidity rates in CHF. Yet, inflammatory markers may early diagnose CHF and predict the prognosis. Excessive salt intake also worsens the inflammation as well as volume control.
PMCID: PMC4109042  PMID: 25177670
Heart Failure; Inflammation; Sodium Dietary
10.  A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation 
PLoS Genetics  2012;8(1):e1002480.
Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process.
Author Summary
Inflammation is a protective response of our organism to harmful stimuli—such as germs, damaged cells, or irritants—and to initiate the healing process. It has also been implicated, with both protective and predisposing effects, in a number of different diseases; but many important details of this complex phenomenon are still unknown. Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the factors and mechanisms underlying inflammation and their consequence on health. Genome-wide association scans (GWAS) have proved successful in revealing robust associations in both common diseases and quantitative traits. Here, we thus performed a multistage GWAS in a large cohort of individuals from Sardinia to examine the role of common genetic variants on the key inflammatory biomarkers Interleukin-6, erythrocyte sedimentation rate, monocyte chemotactic protein-1, and high-sensitivity C-reactive protein. Our work identified new genetic determinants associated with the quantitative levels of these inflammatory biomarkers and confirmed known ones. Overall, the data highlight an intricate regulation of this complex biological phenomenon and reveal proteins and mechanisms that can now be followed up with adequate functional studies.
doi:10.1371/journal.pgen.1002480
PMCID: PMC3266885  PMID: 22291609
11.  Vertebral Bone Mineral Measures and Psychological Wellbeing Among Individuals with Modic Changes 
Purpose
This case-control pilot study examined whether vertebral bone mineral measures were associated with the presence of chronic low back pain (CLBP) and Modic changes (MCs), and to compare psychological wellbeing and inflammation among individuals with CLBP and MCs, compared to individuals with no history of low back pain and without MCs.
Methods
Eleven individuals with MRI-defined MCs in the lumbar spine and CLBP (cases) and 10 individuals with no history of CLBP or MCs (controls) responded to standard questionnaires regarding pain characteristics and psychological health. Bone mineral density (BMD) was measured with postero-anterior and lateral-projection dual energy X-ray absorptiometry (DXA) to estimate areal BMD (aBMD) and apparent volumetric BMD (ap.vBMD). High sensitivity serum C-reactive protein (hsCRP) was measured as an index of inflammation.
Results
While there was no difference between the groups in measures of depression, anxiety and stress, cases reported significantly greater pain catastrophizing attitudes (P < 0.01). hsCRP concentrations did not differ between groups (P = 0.54). Among the 7 cases where MCs were identified between L3–4, significantly higher mean aBMD was observed at the affected vertebral level, compared to the adjacent, unaffected, cephalad level (P = 0.01–0.04), but not when ap.vBMD was calculated (P = 0.36).
Conclusions
Vertebral BMD is not reduced among individuals with CLBP and MCs compared to a control group, although pain catastrophizing attitudes are increased among individuals with CLBP and MCs.
doi:10.4137/CCRep.S9209
PMCID: PMC3320114  PMID: 22493564
Modic change; bone mineral density; hsCRP; psychological health
12.  Postoperative changes of early-phase inflammatory indices after uncomplicated anterior cervical discectomy and fusion using allograft and demineralised bone matrix 
International Orthopaedics  2012;36(11):2293-2297.
Purposes
We investigated sequential levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in uncomplicated ACDF (anterior cervical discectomy and fusion) using allograft and DBM (demineralised bone matrix) for primary cervical spondylosis and/or disc herniation. To our knowledge, there has been no study to investigate the diagnostic value of CRP and ESR for postoperative infection in ACDF using allograft and DBM.
Methods
Blood samples of 85 patients, who underwent one- (n = 51) or two-level (n = 34) ACDF, were obtained and evaluated before surgery and on the first, third, fifth, seventh, 14th, 30th, and 90th postoperative days. No infection was found in any patient for at least one year follow-up period.
Results
Mean CRP value increased significantly on the first postoperative day and reached a peak on the third postoperative day. The peak level rapidly decreased but remained elevated on the fifth, seventh, and 14th postoperative days. Mean ESR value increased significantly and reached a peak on the third postoperative day. The peak level gradually decreased but remained elevated on the fifth and seventh postoperative days. One- and two-level ACDF exhibited similar postoperative changes in CRP and ESR values and no significant difference in mean levels of CRP and ESR throughout the follow-up periods.
Conclusions
This study demonstrates that uncomplicated ACDF using allograft and DBM showed significant abnormal values of CRP and ESR during the early postoperative period. This result suggests that abnormal values of CRP and ESR in the early postoperative period do not indicate acute postoperative infection after ACDF using allograft and DBM. Straying from the normal course, such as a second rise or a failure to decrease, of CRP and ESR is more important to signpost acute postoperative infection in ACDF using allograft and DBM.
doi:10.1007/s00264-012-1645-z
PMCID: PMC3479300  PMID: 22918410
13.  Magnetic resonance imaging findings in low back pain and lower extremity radicular chronic pain 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 37.
Abstract:
Background:
Low back pain (LBP) is one of the most prevalent complaints among the people worldwide. According to the medical statistics, about 80 percent of people have at least one episode of LBP during their lifetime cause them to visit a physician for treatment. LBP is the most prevalent cause of work disability and its related leaves among people under 45 years old. Numerous studies have been conducted on the connection between clinical signs, patients’ complaints, the level of lumbar disc herniation, and abnormal findings of magnetic resonance imaging (MRI). In many cases, contradictory views have been reported and even in some cases canal stenosis and herniated disc have been reported in patient without clinical sings. The aim of this study was to analyze MRI findings in patients with LBP and radicular chronic pain (RCP) attending Imam Reza Hospital (Kermanshah, Iran).
Methods:
This cross-sectional study was conducted on 200 patients (100 with LBP and 100 with RCP). Following unsuccessful results of medical treatment for 1 to 48 months, the examination results, demographic information (age, sex, job, etc.) and their complaints along with MRI findings were documented and statistically analyzed. Patients with history of lumbar surgery, infective inflammatory diseases, fractures, tumors, etc were excluded from the study. To determine the significant correlation between qualitative and quantitative variables, the Chi-Square test and the independent t-test were respectively performed using the statistical package of SPSS (Version 12) The P-value of less than 0.05 was considered significant.
Results:
In the LBP group, patients complained only of posterior and inferior spinal column pain and did not have any pain distribution toward lower limbs or any other signs. However, in the RCP group, in addition to pain distribution towards the lower limbs, they were complaining about muscular myotonia and sensational disorder and 88% also had low back pain. 94 of them were men and 106 were women.106 subjects (80.5%) were urban residents and 39 (19.5%) rural residents. There were 42.5% housewife, 21.5% employee, 15% workers, 9.5% self-employed, and 8.5% were unemployed. In terms of education, 27% were uneducated, 40.5% with incomplete high school diploma, and 32.5% with high school diploma and higher levels of education. 33.5% of patients had the treatment period of one month, while for the rest this period was more than one month to 4 years. Twenty percent did not rest, 52.5% rested up to 3 weeks and 24% rested up to 3 months. In the RCP group, 41% complained of pain in the right leg, 36% in the left leg, and 23% in both legs. However, in the RCP group, 26% had limb paresis, 5% atrophy, 25% some levels of sensational disorders, and 2% had sphincter disorders.
MRI findings:
Herniated disc in the form of protrusion and extrusion at L4-L5 and L5-S1 spaces were mainly observed in patients with RCP rather than those with LBP. Twenty-six patients (13%) had spondylolisthesis of which 12 (46.2%) were in LBP group and the other 14 patients (53.8) in RCP group. Forty-eight patients (24%) had canal stenosis of which 11 patients were from LBP group and 37 from RCP group. Of these 48 patients, 11 had partial stenosis and 37 had absolute stenosis that were in the RCP group.
Conclusions:
The most prevalent herniated disc spaces were at the levels of L4-L5 (87%) and S1-S2 (65%). This is because that most of the movements occur in the mobile parts of disc surface and the stresses that are exerted on the mentioned part. Generally, a meaningful correlation between existence of canal stenosis at L4-L5 and L5-S1 levels and the existence of pressure effect on nerve in THECAL SAC and lat recess in patients with RCP was seen; and also a meaningful correlation among muscular myotonia, radicular distribution of limbs’ pain along with compressive effects on the nerve in the lat recess and the thecal sac and spinal canal stenosis were observed. A significant correlation between complaints of RCP in lower limbs and muscular myotonia with these findings was seen but in analyzing the distributing pain patterns or muscular myotonia on the base of RCP such a correlation was not seen.
Keywords:
Low back pain, Radicular back pain, Magnetic resonance imaging
PMCID: PMC3571563
14.  Fluoroscopic lumbar interlaminar epidural injections in managing chronic lumbar axial or discogenic pain 
Journal of Pain Research  2012;5:301-311.
Among the multiple causes of chronic low back pain, axial and discogenic pain are common. Various modalities of treatments are utilized in managing discogenic and axial low back pain including epidural injections. However, there is a paucity of evidence regarding the effectiveness, indications, and medical necessity of any treatment modality utilized for managing axial or discogenic pain, including epidural injections. In an interventional pain management practice in the US, a randomized, double-blind, active control trial was conducted. The objective was to assess the effectiveness of lumbar interlaminar epidural injections of local anesthetic with or without steroids for managing chronic low back pain of discogenic origin. However, disc herniation, radiculitis, facet joint pain, or sacroiliac joint pain were excluded. Two groups of patients were studied, with 60 patients in each group receiving either local anesthetic only or local anesthetic mixed with non-particulate betamethasone. Primary outcome measures included the pain relief-assessed by numeric rating scale of pain and functional status assessed by the, Oswestry Disability Index, Secondary outcome measurements included employment status, and opioid intake. Significant improvement or success was defined as at least a 50% decrease in pain and disability. Significant improvement was seen in 77% of the patients in Group I and 67% of the patients in Group II. In the successful groups (those with at least 3 weeks of relief with the first two procedures), the improvement was 84% in Group I and 71% in Group II. For those with chronic function-limiting low back pain refractory to conservative management, it is concluded that lumbar interlaminar epidural injections of local anesthetic with or without steroids may be an effective modality for managing chronic axial or discogenic pain. This treatment appears to be effective for those who have had facet joints as well as sacroiliac joints eliminated as the pain source.
doi:10.2147/JPR.S32699
PMCID: PMC3442746  PMID: 23055773
lumbar disc herniation; axial or discogenic pain; lumbar interlaminar epidural injections; local anesthetic; steroids; controlled comparative local anesthetic blocks; NCT00681447
15.  Hypersensitivity to Rabbit Antithymocyte Globulin in an Islet Transplant Recipient: A Case Report 
Transplantation proceedings  2011;43(9):3302-3306.
Objective
The aim was to describe a case of hypersensitivity to rabbit antithymocyte globulin (rATG) occurring in the context of islet transplantation.
Methods
A 36-year-old woman with type 1 diabetes was admitted for islet transplantation. rATG was administered the first day (1.5 mg/kg) with methylprednisolone (2 mg/kg), and on the second day (1.5 mg/kg) without glucocorticoid to avoid potential toxicity to the anticipated islet transplant.
Results
At the end of the rATG infusion on the second day she developed hives over her face, chest, and back and tender erythema at her intravenous site (Arthus reaction). Islet transplantation was not performed. She reported exposure to a pet rabbit for 2 years in childhood. Overnight, fever developed and the rash evolved into an erythematous morbilliform eruption affecting the torso. Serum high-sensitivity C-reactive protein (hsCRP) and the erythrocyte sedimentation rate (ESR) were elevated; serum complements C3 and C4 were normal. She received prednisone (50 mg) with subsequent resolution of the rash. Nine days after her initial reaction, she developed a recurrence of the rash and fever with arthralgias; levels of C3 and C4 had fallen. Methylprednisolone (125 mg, twice) was required for symptom improvement, and was gradually tapered as prednisone over the next 4 weeks with resolution of the complement, ESR, and hsCRP abnormalities. Five months after the initial attempt at islet transplantation, she returned to receive 7,879 IE/kg via portal vein infusion under basiliximab, etanercept, tacrolimus, and sirolimus immunosuppression and has required no to low-dose (0.1 U/kg/d) insulin to maintain near-normal glycemic control for > 12 months after transplantation.
Conclusions
Our patient’s initial hypersensitivity reaction to rATG was followed by immune-complex type 3 hypersensitivity (serum sickness) requiring high-dose glucocorticoids. Canceling the initial islet infusion proved to be wise, and the patient subsequently did well with islet transplantation under an alternative induction agent.
doi:10.1016/j.transproceed.2011.10.004
PMCID: PMC3234161  PMID: 22099783
16.  C-reactive Protein and Risk of Colorectal Adenoma According to Celecoxib Treatment 
Background
Inflammation, as measured by the circulating inflammatory marker high sensitivity C-reactive protein (hsCRP), has been associated with cardiovascular disease. However, data regarding CRP and risk of colorectal cancer have been conflicting. The Adenoma Prevention with Celecoxib (APC) trial demonstrated that the anti-inflammatory drug celecoxib prevents recurrence of colorectal adenoma but increases risk of cardiovascular events. We examined if serum hsCRP modified these results.
Methods
We measured hsCRP from serum specimens provided at study entry by patients enrolled in the APC trial. Patients were stratified according to use of low-dose aspirin, randomized to receive three years of treatment with placebo, 200-mg-bid celecoxib, or 400-mg-bid celecoxib, and underwent follow-up colonoscopies at Year 1 and 3.
Results
Among 1,680 patients, the estimated three-year cumulative incidence of adenoma was 42% for patients with hsCRP <1mg/L, compared with 43% (RR=1.02; 95% confidence interval (CI)=0.85–1.22) for hsCRP 1–3mg/L, and 41% (RR=1.1; CI=0.90–1.34) for hsCRP >3mg/L. The effect of celecoxib on adenoma recurrence did not vary among patients with high (>3mg/L) compared with low (≦3mg/L) hsCRP. However, among patients with high hsCRP, the RR of cardiovascular events compared with placebo was 2.27 (95%CI=0.72–7.14) for those randomized to celecoxib 200-mg-bid and 3.28 (CI=1.09–9.91) for 400-mg-bid. In contrast, among patients with low hsCRP, the corresponding RRs were 0.99 (CI=0.53–1.83) and 1.11 (CI=0.61–2.02).
Conclusions
HsCRP may predict risk of celecoxib-associated cardiovascular toxicity, but not adenoma recurrence or celecoxib treatment efficacy. Patients with low hsCRP may be a subgroup with a favorable risk-benefit profile for celecoxib chemoprevention.
doi:10.1158/1940-6207.CAPR-10-0403
PMCID: PMC3151679  PMID: 21816845
Adenoma; celecoxib; c-reactive protein; inflammation; chemoprevention
17.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Background
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
Conclusions
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Background
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000047.
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
doi:10.1371/journal.pmed.1000047
PMCID: PMC2661253  PMID: 19360087
18.  Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings 
Asian Spine Journal  2013;7(4):322-334.
Study Design
Cross sectional and observational.
Purpose
To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms.
Overview of Literature
Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing.
Methods
This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded.
Results
During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%).
Conclusions
Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life.
doi:10.4184/asj.2013.7.4.322
PMCID: PMC3863659  PMID: 24353850
Claudication; Low back pain; Spondylolisthesis
19.  Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein 
Annals of the Rheumatic Diseases  2004;63(2):200-205.
Background: Although osteoarthritis (OA) is thought to derive from defective chondrocyte metabolism and thus inherently lack the large scale systemic response of rheumatoid arthritis, there is increasing interest in the acute phase proteins in OA.
Objective: To assess the association between high sensitivity C reactive protein (hsCRP) and severity and extent of OA in patients with advanced hip and knee OA.
Methods: Preoperative hsCRP was measured in frozen serum samples from 770 consecutive patients with hip or knee joint replacement due to advanced OA recruited between 1995 and 1996. Pain was measured by a visual analogue scale and the Western Ontario and McMaster Universities OA index (WOMAC). The extent of OA in different joints was assessed clinically and radiographically.
Results: The (geometric) mean hsCRP was 2.5 mg/l among all patients. Severity of pain was associated with mean hsCRP (adjusted elevation highest v lowest quintile = 35%, p = 0.01) after controlling for known or suspected predictors of hsCRP, including age, smoking, and body mass index. Neither the bilateral nor the generalised extent of OA, nor any of the dimensions of the WOMAC were associated with mean hsCRP levels.
Conclusions: Severity of pain, but not extent of OA, was associated with hsCRP levels in this group of patients with advanced OA. Longitudinal studies with repeated assessments of hsCRP and pain are needed to assess the possible value of hsCRP for monitoring or predicting the clinical course of OA.
doi:10.1136/ard.2003.007674
PMCID: PMC1754873  PMID: 14722211
20.  Low back pain (chronic) 
Clinical Evidence  2010;2010:1116.
Introduction
Over 70% of people in developed countries develop low back pain (LBP) at some time. But recovery is not always favourable: 82% of non recent-onset patients still experience pain 1 year later. Many patients with chronic LBP who were initially told that their natural history was good spend months or years seeking relief.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatments? What are the effects of injection therapy? What are the effects of non-drug treatments? What are the effects of non-surgical and surgical treatments? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 64 systematic reviews or RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture, analgesics, antidepressants, back schools, behavioural therapy, electromyographic biofeedback, exercise, injections (epidural corticosteroid injections, facet joint injections, local injections), intensive multidisciplinary treatment programmes, lumbar supports, massage, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), non-surgical interventional therapies (intradiscal electrothermal therapy, radiofrequency denervation), spinal manipulative therapy, surgery, traction, and transcutaneous electrical nerve stimulation (TENS).
Key Points
Over 70% of people in developed countries develop low back pain at some time, which usually improves within 2 weeks, however about 10% remained off work and about 20% had persistent symptoms at 1 year.
Non-steroidal anti-inflammatory drugs (NSAIDs) may be more effective than placebo at improving pain intensity in people with chronic low back pain.
Opioid analgesics (with or without paracetamol) may improve pain and function compared with placebo. However, long-term use of NSAIDs or opioids may be associated with well-recognised adverse effects. We don't know whether antidepressants decrease chronic low back pain or improve function compared with placebo in people with or without depression. Benzodiazepines may improve pain, but studies of non-benzodiazepine muscle relaxants have given conflicting results.
CAUTION: Since the last update of this review, a drug safety alert has been issued on increased suicidal behaviour with antidepressants (www.fda.gov/medwatch).
We don't know whether epidural corticosteroid injections or local injections with corticosteroids and local anaesthetic improve chronic low back pain in people without sciatica. Facet-joint corticosteroid injections may be no more effective than placebo at reducing pain.
Fusion surgery is more effective than standard rehabilitation for improving pain in people with chronic non-radicular low back pain, but it is no better than intensive rehabilitation with a cognitive behavioural component.
Exercise improves pain and function compared with other conservative treatments.
Intensive multidisciplinary treatment programmes improve pain and function compared with usual care, but less-intensive programmes do not seem beneficial.
Acupuncture, back schools, behavioural therapy, and spinal manipulation may reduce pain in the short term, but effects on function are unclear.
Massage may improve pain and function compared with sham or other active treatment.
We don't know whether electromyographic biofeedback, lumbar supports, traction, or TENS improve pain relief.
We also don't know whether intradiscal electrothermal therapy, radiofrequency denervation, or disc replacement improve pain relief or function.
PMCID: PMC3217809  PMID: 21418678
21.  Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis 
Background:
C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT).
Aim:
This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT.
Materials and Methods:
Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves’ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens’ method. Either Tc99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves’ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients.
Results:
Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves’ group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR.
Conclusion:
There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves’ disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves’ disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT.
doi:10.4103/2230-8210.103002
PMCID: PMC3510970  PMID: 23226645
C-reactive protein; Graves’; sub-acute thyroiditis; thyroiditis
22.  Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein for the Diagnosis of Giant Cell Arteritis 
Objectives
1) To evaluate the utility of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for the diagnosis of giant cell arteritis (GCA) 2) to determine the frequency of normal ESR and CRP at diagnosis of GCA.
Methods
All patients undergoing temporal artery biopsy (TAB) between 2000 and 2008 were identified. Only subjects with both ESR and CRP at the time of TAB were included. The medical records of all patients were reviewed.
Results
We included 764 patients (65% women), mean age 72.7 (±9.27) years, who underwent TAB. Biopsy was consistent with GCA in 177 patients (23%). Elevated CRP and elevated ESR provided a sensitivity of 86.9% and 84.1% respectively, for a positive TAB. The odds ratio (OR) of a concordantly elevated ESR and CRP for positive TAB was 3.06 (95% CI 2.03, 4.62) while the OR for concordantly normal ESR and CRP was 0.49 (95% CI 0.29, 0.83).
Seven patients (4%) with a positive TAB for GCA had a normal ESR and CRP at diagnosis. Compared to GCA patients with elevated markers of inflammation, a greater proportion of these patients had polymyalgia rheumatica symptoms (p=0.008) while constitutional symptoms, anemia and thrombocytosis were observed less often (p<0.05).
Conclusions
CRP is a more sensitive marker than ESR for a positive TAB that is diagnostic of GCA. There may be clinical utility in obtaining both tests in the evaluation of patients with suspected GCA. A small proportion of patients with GCA may have normal inflammatory markers at diagnosis.
doi:10.1016/j.semarthrit.2011.10.005
PMCID: PMC3307891  PMID: 22119103
23.  Influence of preoperative nucleus pulposus status and radiculopathy on outcomes in mono-segmental lumbar total disc replacement: results from a nationwide registry 
Background
Currently, herniated nucleus pulposus (HNP) with radiculopathy and other preconditions are regarded as relative or absolute contraindications for lumbar total disc replacement (TDR). In Switzerland it is left to the surgeon's discretion when to operate. The present study is based on the dataset of SWISSspine, a governmentally mandated health technology assessment registry. We hypothesized that preoperative nucleus pulposus status and presence or absence of radiculopathy has an influence on clinical outcomes in patients treated with mono-segmental lumbar TDR.
Methods
Between March 2005 and April 2009, 416 patients underwent mono-segmental lumbar TDR, which was documented in a prospective observational multicenter mode. The data collection consisted of perioperative and follow-up data (physician based) and clinical outcomes (NASS, EQ-5D).
Patients were divided into four groups according to their preoperative status: 1) group degenerative disc disease ("DDD"): 160 patients without HNP and no radiculopathy, classic precondition for TDR; 2) group "HNP-No radiculopathy": 68 patients with HNP but without radiculopathy; 3) group "Stenosis": 73 patients without HNP but with radiculopathy, and 4) group "HNP-Radiculopathy": 132 patients with HNP and radiculopathy. The groups were compared regarding preoperative patient characteristics and pre- and postoperative VAS and EQ-5D scores using general linear modeling.
Results
Demographics in all four groups were comparable. Regarding the improvement of quality of life (EQ-5D) there were no differences across the four groups. For the two main groups DDD and HNP-Radiculopathy no differences were found in the adjusted postoperative back- and leg pain alleviation levels, in the stenosis group back- and leg pain relief were lower.
Conclusions
Despite higher preoperative leg pain levels, outcomes in lumbar TDR patients with HNP and radiculopathy were similar to outcomes in patients with the classic indication; this because patients with higher preoperative leg pain levels benefit from a relatively greater leg pain alleviation. The group with absence of HNP but presence of radiculopathy showed considerably less benefits from the operation, which is probably related to ongoing degenerative processes of the posterior segmental structures. This observational multicenter study suggests that the diagnoses HNP and radiculopathy, combined or alone, may not have to be considered as absolute or relative contraindications for mono-segmental lumbar TDR anymore, whereas patients without HNP but with radiculopathy seem to be suboptimal candidates for the procedure.
doi:10.1186/1471-2474-12-275
PMCID: PMC3250959  PMID: 22136141
24.  Relationship between low-back pain, muscle spasm and pressure pain thresholds in patients with lumbar disc herniation 
European Spine Journal  2005;15(1):41-47.
It is not known whether or not muscle spasm of the back muscles presented in patients with sciatic scoliosis caused by lumbar disc herniation produces muscle pain and/or tenderness. Pressure pain thresholds (PPTs) of the lower back and low-back pain were examined in 52 patients (13 of 52 presenting sciatic scoliosis) with lumbar disc herniation who complained of radicular pain and in 15 normal subjects. PPTs were measured at five points bilaterally using an electronic pressure algometer. Low-back pain was evaluated using visual analogue scale (VAS) ratings. All patients complained of radicular leg pain and were divided into the following three groups according to the presence of and the region of low-back pain: no low-back pain group, low-back pain with no laterality group, and low-back pain dominantly on the herniation side group; the VAS rating on the side ipsilateral to the herniation side was higher than that on the contralateral side. In the normal subjects, there were no statistically significant differences between sides in mean PPTs at all sites examined. PPTs were not lower in the spasmodic side (concave side) than the convex side in patients with sciatic scoliosis. PPTs on the herniation side were significantly lower than those on the contralateral side in patients with low-back pain dominantly on the herniation side. Furthermore, the areas of low PPTs were beyond the innervation area of dorsal ramus of L5 and S1 nerve root. It was considered that not only the peripheral mechanisms but also the hyper excitability of the central nervous system might contribute in lowering PPTs of the lower back on the herniation side.
doi:10.1007/s00586-004-0813-2
PMCID: PMC3454558  PMID: 15931510
Pressure pain threshold; Muscle spasm; Low-back pain; Lumbar disc herniation; Sciatic scoliosis
25.  Disc degeneration of cervical spine on MRI in patients with lumbar disc herniation: comparison study with asymptomatic volunteers 
European Spine Journal  2010;20(4):585-591.
An association between progression of cervical disc degeneration and that of lumbar disc degeneration has been considered to exist. To date, however, this association has not yet been adequately studied. Age-related changes in the cervical intervertebral discs were evaluated by magnetic resonance imaging (MRI) in patients with lumbar disc herniation, and compared with the MRI findings of healthy volunteers without lower back pain. The purpose of this study was to clarify whether the prevalence of asymptomatic cervical disc degeneration is higher in patients with lumbar disc herniation than in healthy volunteers. The study was conducted on 51 patients who were diagnosed as having lumbar disc herniation and underwent cervical spine MRI. The patients consisted of 34 males and 17 females ranging in age from 21–83 years (mean 46.9 ± 14.5 years) at the time of the study. The control group was composed of 113 healthy volunteers (70 males and 43 females) aged 24–77 years (mean 48.9 ± 14.7 years), without neck pain or low back pain. The percentage of subjects with degenerative changes in the cervical discs was 98.0% in the lumbar disc herniation group and 88.5% in the control group (p = 0.034). The presence of lumbar disc herniation was associated significantly with decrease in signal intensity of intervertebral disc and posterior disc protrusion in the cervical spine. None of the MRI findings was significantly associated with the gender, smoking, sports activities, or BMI. As compared to healthy volunteers, patients with lumbar disc herniation showed a higher prevalence of decrease in signal intensity of intervertebral disc and posterior disc protrusion on MRI of the cervical spine. The result of this study suggests that disc degeneration appears to be a systemic phenomenon.
doi:10.1007/s00586-010-1644-y
PMCID: PMC3065617  PMID: 21127918
Lumbar disc herniation; Asymptomatic volunteers; MRI; Cervical spine; Disc degeneration

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