***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background Few studies have investigated prognostic factors for patients with sciatica , especially for patients treated without surgery . The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica . Methods The study was a prospect i ve multicentre observational study including 466 patients with sciatica and lumbar disc herniation . Potential prognostic factors were sociodemographic characteristics , back pain history , kinesiophobia , emotional distress , pain , comorbidity and clinical examination findings . Study participation did not alter treatment considerations for the patients in the clinics . Patients reported on the question naires if surgery of the disc herniation had been performed . Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success , defined as Maine – Seattle Back Question naire score of ≥5 ( 0–12 ) ( primary outcome ) and Sciatica Bothersomeness Index ≥7 ( 0–24 ) ( secondary outcome ) . Results Rates of non-success were at 1 and 2 years 44 % and 39 % for the main outcome and 47 % and 42 % for the secondary outcome . Approximately 1/3 of the patients were treated surgically . For the main outcome variable , in the final multivariate model non-success at 1 year was significantly associated with being male ( OR 1.70 [ 95 % CI ; 1.06 − 2.73 ] ) , smoker ( 2.06 [ 1.31 − 3.25 ] ) , more back pain ( 1.0 [ 1.01 − 1.02 ] ) , more comorbid subjective health complaints ( 1.09 [ 1.03 − 1.15 ] ) , reduced tendon reflex ( 1.62 [ 1.03 − 2.56 ] ) , and not treated surgically ( 2.97 [ 1.75 − 5.04 ] ) . Further , factors significantly associated with non-success at 2 years were duration of back problems > ; 1 year ( 1.92 [ 1.11 − 3.32 ] ) , duration of sciatica > ; 3 months ( 2.30 [ 1.40 − 3.80 ] ) , more comorbid subjective health complaints ( 1.10 [ 1.03 − 1.17 ] ) and kinesiophobia ( 1.04 [ 1.00 − 1.08 ] ) . For the secondary outcome variable , in the final multivariate model , more comorbid subjective health complaints , more back pain , muscular weakness at clinical examination , and not treated surgically , were independent prognostic factors for non-success at both 1 and 2 years . Conclusions The results indicate that the prognosis for sciatica referred to secondary care is not that good and only slightly better after surgery and that comorbidity should be assessed in patients with sciatica . This calls for a broader assessment of patients with sciatica than the traditional clinical assessment in which mainly the physical symptoms and signs are investigated Most common human traits and diseases have a polygenic pattern of inheritance : DNA sequence variants at many genetic loci influence the phenotype . Genome-wide association ( GWA ) studies have identified more than 600 variants associated with human traits , but these typically explain small fractions of phenotypic variation , raising questions about the use of further studies . Here , using 183,727 individuals , we show that hundreds of genetic variants , in at least 180 loci , influence adult height , a highly heritable and classic polygenic trait . The large number of loci reveals patterns with important implication s for genetic studies of common human diseases and traits . First , the 180 loci are not r and om , but instead are enriched for genes that are connected in biological pathways ( P = 0.016 ) and that underlie skeletal growth defects ( P < 0.001 ) . Second , the likely causal gene is often located near the most strongly associated variant : in 13 of 21 loci containing a known skeletal growth gene , that gene was closest to the associated variant . Third , at least 19 loci have multiple independently associated variants , suggesting that allelic heterogeneity is a frequent feature of polygenic traits , that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified . Fourth , associated variants are enriched for likely functional effects on genes , being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes . Our data explain approximately 10 % of the phenotypic variation in height , and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16 % of phenotypic variation ( approximately 20 % of heritable variation ) . Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully , our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways The endogenous opioid system is involved in stress responses , in the regulation of the experience of pain , and in the action of analgesic opiate drugs . We examined the function of the opioid system and μ-opioid receptors in the brains of healthy human subjects undergoing sustained pain .  Sustained pain induced the regional release of endogenous opioids interacting with μ-opioid receptors in a number of cortical and subcortical brain regions . The activation of the μ-opioid receptor system was associated with reductions in the sensory and affective ratings of the pain experience , with distinct neuroanatomical involvements . These data demonstrate the central role of the μ-opioid receptors and their endogenous lig and s in the regulation of sensory and affective components of the pain experience Study Design . A prospect i ve analysis of patients with lumbar disc herniation ( LDH ) . Objectives . To determine the role of neuropeptides as a biochemical signature of pain states in patients with LDH . Summary of Background Data . Increases in the plasma level of neuropeptides have been reported in patients suffering from a variety of painful conditions . However , there is no such report on patients with LDH . Methods . From a total of 27 patients with a single-level LDH , blood sample s were collected before and 3 weeks after lumbar discectomy .  Plasma levels of alpha calcitonin gene-related peptide ( CGRP ) , galanin , neuropeptide Y , and substance P were determined by using enzyme-linked immunosorbent assay . The association or correlation between preoperative concentration of plasma neuropeptides and gender , patients ’ age , and VAS were analyzed statistically . Also , the concentration of plasma neuropeptides was compared before and after lumbar discectomy . Results . Preoperative plasma levels of CGRP were correlated significantly with the extent of sciatica as determined by VAS . In addition , plasma levels of CGRP and galanin significantly decreased after lumbar discectomy in line with the disappearance of pain symptoms . Conclusions . These findings indicate the role of plasma CGRP and possibly galanin as a systemic neurochemical signature of pain states in patients with LDH Background Earlier observations show that development of persistent pain may be associated with the genetic variability in the gene encoding for the μ-opioid receptor 1 , the OPRM1 A118 G ( rs1799971 ) . The aim of this study was to investigate the association between OPRM1 genotype and subjective health complaints in patients with radicular pain and disc herniation . Methods A prospect i ve , 1-year observational study was conducted at a hospital back clinic , including 118 Caucasian patients with lumbar radicular pain and MRI confirmed disc herniation .  Single nucleotide polymorphism genotyping regarding the OPRM1 A118 G was performed . The data of individuals with AA versus AG or GG were analysed separately by linear mixed models . The Subjective Health Complaints Inventory  ( 0 - 81 ) including 27 common complaints experienced the previous month on a scale from not at all ( 0 ) to severe ( 3 ) was used as outcome . Pain , prior duration of leg pain , age , smoking status , and lumbar disc surgery were considered as covariates . Results In total 23 of 118 patients were carriers of the OPRM1 G-allele . All patients except female carriers of the G-allele reported a decrease in pain from baseline to 1 year . Female carriers of the G-allele reported significantly higher subjective health complaints score during the study time span than male carriers of the G-allele when controlling for pain and pain duration . Conclusion The present data indicate that , when controlling for pain intensity and duration , subjective health complaints are associated with a sex - OPRM1 A118 G polymorphism interaction in patients with radicular pain Study Design . Prospect i ve observational cohort . Objective . Correlate epidural inflammatory cytokines with the clinical response to  epidural steroid injection  in patients with lumbar nerve root irritation . Summary of Background Data . Some back pain syndromes are thought to be associated with activation of inflammatory pathways and others may be associated with primary mechanical derangements . Human studies providing detailed evidence for the primary inflammatory causation , which may be best treated with anti-inflammatory strategies , are lacking . There are currently no accurate diagnostic tests to predict the response to epidural steroid injection or surgical intervention in back pain and sciatica syndromes . Methods . Forty-seven consecutive patients with lumbar degenerative changes and low back and /or leg pain were prospect ively enrolled . An epidural lavage was performed , followed by injection of marcaine/depo-medrol . Subjects scored their pain before and 3 months after the procedure . The immunoreactivity of an array of cytokines was measured in lavage sample s and compared with clinical response to the therapeutic injection . Ten subjects underwent repeat epidural lavage sampling 3 months after the steroid injection . Results . Interferon gamma ( IFN&ggr ; ) was the most consistently detected cytokine . IFN&ggr;-immunoreactivity also highly correlated with reported reduction of pain 3-months after the epidural steroid injection . In subjects reporting significant pain relief ( > 50 % ) from the injection , mean [ IFN&ggr ; ] was significantly greater compared with patients experiencing no significant relief . The IFN&ggr;-immunoreactivity in repeat lavage sample s decreased to trace residual concentrations in patients who reported pain relief from the steroid injection . Conclusion . The presence of epidural IFN&ggr;-immunoreactivity corresponding to > 10 pg/mL predicted significant pain relief after epidural steroid injection with > 95 % accuracy . These results suggest that IFN&ggr ; may be part of a biochemical cascade triggering pain in sciatica ; IFN&ggr;-immunoreactivity may aid as a biomarker for predicting the response to steroid therapy and /or surgical intervention , and may serve as a future therapeutic target In this prospect i ve longitudinal study with a follow-up of 6 months , the course of serum concentration of C-reactive protein was measured by an ultrasensitive immunoassay in 31 patients with acute lumbosciatic pain and 41 patients with chronic low back pain .  High-sensitive CRP ( hsCRP ) , pain and clinical function were assessed at ten fixed time-points during follow-up . The course of  hsCRP values was assessed in relation to the course of pain and clinical function adjusting for possible confounding factors . At the beginning of the study , there were no statistically significant differences in mean hsCRP levels in patients with acute lumbosciatic pain ( 1.49mg/l ) compared to the levels obtained in patients with chronic low back pain ( 1.30mg/l ) and those in a control group from the general population ( 1.26mg/l ) . In patients with acute lumbosciatic pain , hsCRP declined significantly in the initial period of 3 weeks with a corresponding decrease in pain and improvement in function and clinical evaluation as assessed with the straight leg raising test ( SLR ) , whereas after this period , the course of the hsCRP did not correspond with the clinical parameters . In patients with chronic low back pain , hsCRP remained approximately constant throughout the whole period with no correlation with pain or function . As a conclusion , according to this study levels of hsCRP do not have a major clinical relevance when evaluating the long-term course of patients with acute lumbosciatic pain and chronic low back pain and therefore should not be taken into primary consideration when decisions on therapy are made AIMS We have shown in a cross-sectional setting that an IL6 haplotype ( GGGA ) is associated with intervertebral disc disease ( IDD ) characterized by sciatica . The aim of this study was to evaluate the prognostic role of the GGGA haplotype in IDD . METHODS DNA from 153 sciatica patients who participated in a r and omized controlled trial of periradicular infiltration  was analysed for IL6 variations rs1800797 ( -596A > G ) , rs1800796 ( -572G > C ) , rs1800795 ( -174G > C ) , and rs13306435 ( + 15T > A ) . The patients recorded back and leg pain intensity and duration , disability by Oswestry Index and back-related sickness absence over a three-year follow-up . Repeated measures and univariate analysis of variance with adjustment for age , gender and physical work load were used in statistical analyses for the last two-years of the follow-up . RESULTS The prevalence of the GGGA haplotype was 9 % ( 14/153 ) . Subjects with the GGGA haplotype did not differ from those without the haplotype with respect to pain intensity , or disability score , but days with back and leg pain and days on sick leave were significantly higher among subjects with the IL6 haplotype after adjustment for occupation ( p=0.006 , 0.001 and 0.002 
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Conclusion The present results indicate that several genetic factors and biomarkers may predict slow recovery in LRP .