Candidate Biomarkers to Distinguish Spinal Tuberculosis From Mechanical Back Pain in a Tuberculosis Endemic Setting.

Background: Spinal tuberculosis (TB) may have a variable, non-specific presentation including back pain with- or without- constitutional symptoms. Further tools are needed to aid early diagnosis of this potentially severe form of TB and immunological biomarkers may show potential in this regard. The aim of this study was to investigate the utility of host serum biomarkers to distinguish spinal TB from mechanical back pain. Methods: Patients with suspected spinal TB or suspected mechanical back pain were recruited from a tertiary hospital in the Western Cape, South Africa, and provided a blood sample for biomarker analysis. Diagnosis was subsequently confirmed using bacteriological testing, advanced imaging and/or clinical evaluation, as appropriate. The concentrations of 19 host biomarkers were evaluated in serum samples using the Luminex platform. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to identify biomarkers with the potential to distinguish spinal TB from mechanical back pain. Results: Twenty-six patients with spinal TB and 17 with mechanical back pain were recruited. Seven out of 19 biomarkers were significantly different between groups, of which Fibrinogen, CRP, IFN-γ and NCAM were the individual markers with the highest discrimination utility (Area Under Curve ROC plot 0.88-0.99). A five-marker biosignature (CRP, NCAM, Ferritin, CXCL8 and GDF-15) correctly classified all study participants after leave-one-out cross-validation. Conclusion: This study identified host serum biomarkers with the potential to diagnose spinal TB, including a five-marker biosignature. These preliminary findings require validation in larger studies.

Primary Sjögren's syndrome manifesting as sclerotic metabolic bone disease.

Primary Sjögren's syndrome (pSS) is a chronic slowly progressive autoimmune disease characterised by lymphocytic infiltration of salivary and lacrimal glands with varying degree of systemic involvement. Renal involvement, a recognised extraglandular manifestation of pSS, is commonly related to tubular dysfunction and generally manifests as distal renal tubular acidosis (RTA), proximal RTA, tubular proteinuria and nephrogenic diabetes insipidus. Untreated long-standing RTA is known to cause metabolic bone disease. Here, we present the report of a patient with sclerotic metabolic bone disease related to pSS with combined distal and proximal RTA and negative workup for other causes of sclerotic bone disease. A significant clinical and biochemical improvement, including recovery of proximal tubular dysfunction, was noted with alkali therapy. This case suggests the need to consider pSS in the diagnostic algorithm of a patient presenting with sclerotic bone disease.

Altered Gut Microbiota Composition Is Associated With Back Pain in Overweight and Obese Individuals.

Background: Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. Aims and Methods: We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Results: Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with (n = 14) or without (n = 22) back pain. Individuals with back pain had a higher abundance of the genera Adlercreutzia (p = 0.0008; FDR = 0.027), Roseburia (p = 0.0098; FDR = 0.17), and Uncl. Christensenellaceae (p = 0.02; FDR = 0.27) than those without back pain. Adlercreutzia abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. Adlercreutzia was positively correlated with BMI (rho = 0.35, p = 0.03), serum adipsin (rho = 0.33, p = 0.047), and serum leptin (rho = 0.38, p = 0.02). Conclusions: Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering Adlercreutzia abundance to treat back pain.

Extreme lateral interbody fusion and percutaneous pedicle screw fixation in the minimally invasive treatment of thoracic tuberculosis.

OBJECTIVE: As a minimally invasive intervertebral fusion technique popularized in recent years, extreme lateral interbody fusion (XLIF) has various advantages. In this study, we describe the application and efficacy of XLIF for the treatment of thoracic tuberculosis (TB), as this may be an emerging treatment option for thoracic TB in the future. METHODS: We present the case of a 75-year-old man who had suffered from chest and back pain for 1 month. Imaging studies showed destruction of the T12 and L1 vertebral bodies and the T12-L1 intervertebral disc, accompanied by formation of a paravertebral abscess. After 2 weeks of standard anti-TB treatment, the patient underwent debridement of the lesions, XLIF, and percutaneous pedicle screw fixation. RESULTS: The patient's chest and back pain were significantly alleviated after the operation. The patient recovered well, and as of the most recent follow-up had no obvious limitation in thoracolumbar spine function. CONCLUSIONS: XLIF combined with percutaneous pedicle screw fixation for the treatment of thoracic TB can allow for TB lesion debridement, discectomy, and interbody fusion under direct visualization, and can effectively improve patient prognosis.

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

Spa therapy induces clinical improvement and protein changes in patients with chronic back pain.

This study is primarily aimed at assessing serum changes on a large panel of proteins in patients with chronic back pain following spa therapy, as well as evaluating different spa therapy regimens as a preliminary exploratory clinical study. Sixty-six patients with chronic back pain secondary to osteoarthritis were randomly enrolled and treated with daily mud packs and bicarbonate-alkaline mineral water baths, or a thermal hydrotherapy rehabilitation scheme, the combination of the two regimens or usual medication only (control group), for two weeks. Clinical variables were evaluated at baseline, after 2 and 12 weeks. One thousand serum proteins were tested before and after a two-week mud bath therapy. All spa treatment groups showed clinical benefit as determined by improvements in VAS pain, Roland Morris disability questionnaire and neck disability index at both time points. The following serum proteins were found greatly increased (≥2.5 fold) after spa treatment: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). Three proteins were found greatly decreased (≤0.65 fold): apolipoprotein C-III (Apoc3), interleukin 23 alpha subunit p19 (IL23A) and syndecan-1 (SDC1). Spa therapy was confirmed as beneficial for chronic back pain and proved to induce changes in proteins involved in functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response.

Spinal IgG4-Related Hypertrophic Pachymeningitis with Spinal Cord Compression: Case Report and Literature Review.

BACKGROUND: Back pain is a leading reason for patients to seek medical attention. Although musculoskeletal causes are common, patients can also present with rarer etiologies. CASE DESCRIPTION: A 50-year-old man presented with 2 months of isolated upper back pain initially suspected to be secondary to overuse muscular strain. During the next 3 months, his pain worsened, and he developed lower extremity dysesthesia and subjective weakness, despite normal neurological examination findings. Nonrevealing laboratory workup included normal muscle enzymes, C-reactive protein, urinalysis, and human leukocyte antigen B27. Magnetic resonance imaging revealed a normal brain but a hypointense C7-T5 epidural mass, prompting a neurosurgical recommendation for laminectomy with evacuation of the suspected hematoma. His symptoms fully and promptly resolved after a 5-day course of prednisone 40 mg. When his symptoms recurred within 2 months, he underwent T4-T5 laminectomy with biopsy of a mass confluent with the dura mater. Initial pathological examination revealed fibrotic tissue of unclear etiology with polyclonal lymphoid infiltrate but no malignant cells, vasculitis, or granulomas. After months of recurrent, steroid-responsive symptoms, he presented to the rheumatology clinic. Repeat spinal magnetic resonance imaging demonstrated progression of epidural thickening with suspected spinal cord compression. Previous biopsy samples were then immunostained for IgG4, revealing focally dense IgG4-positive plasma cells, up to 29 cells per high power field, consistent with spinal IgG4-related hypertrophic pachymeningitis. He began rituximab therapy with a prednisone taper and demonstrated symptomatic and neurologic improvement with successful withdrawal from corticosteroids. CONCLUSIONS: To the best of our knowledge, the present case represents the 12th reported case of spinal IgG4-related hypertrophic pachymeningitis. An early diagnosis and treatment could prevent progression to permanent neurological impairment and functional disability.

Blood monoamines as potential biomarkers for conditioned pain modulation efficacy: An exploratory study in paediatrics.

BACKGROUND: Monoaminergic pathways are involved in the process of pain inhibition and facilitation. The objective of this study was to investigate the role of blood monoamines as biomarkers of conditioned pain modulation (CPM) efficacy. METHODS: One hundred and five paediatric patients with chronic back pain were enrolled in this observational study. The protocol involved dosage of plasma monoamines (dopamine, DOPA; serotonin, 5-HT; epinephrine, Epi; norepinephrine, NE; metanephrine, ME; and normetanephrine, NME) and clinical assessment (CPM, functional disability, pain, sleep quality, anxiety and depression). RESULTS: 5-HT and DOPA were positively correlated among each other and were both negatively correlated with Epi, ME, NE and NME. CPM presented a positive correlation with DOPA and 5-HT. On the other hand, Epi, ME, NE and NME correlated negatively with CPM. Different correlation coefficients were observed between genders, with stronger coefficients being observed in the male subpopulation. Stepwise regression controlling for age and gender indicated that ME (B = -0.987, SE(B) = 0.299, p = 0.002) was the only significant predictor for CPM efficacy. Higher blood ME was associated with poorer CPM efficacy. ME explained 53% of variation of CPM in males (R2  = 0.536, p < 0.0001) and 7% in females (R2  = 0.074, p = 0.014). In males, blood ME >15 pg/ml predicted inefficient CPM with 88.9% sensitivity and 83.3% specificity. CONCLUSIONS: Our findings suggest that ME can be a potential biomarker for CPM efficacy in paediatrics. Future studies are needed to assess the efficacy of tailored treatments for pain according to blood ME. SIGNIFICANCE: We were able to demonstrate an association between CPM and circulating monoamines. In the clinical setting, sampling ME could provide the clinician an idea of the individual's pain modulation potential. This may be particularly important for children with cognitive impairment, for whose CPM paradigm cannot be used.

Case-based roundtable on treatment approach for young, fit, newly diagnosed multiple myeloma patients.

With the advent new proteasome inhibitors (carfilzomib, ixazomib), new immune-modulatory drugs (pomalidomide), and new monoclonal antibodies (elotuzimab, daratumumab) as approved treatments for myeloma, the therapeutic landscape for this disease has changed. In this chapter, using a case-based approach, I will provide a personal guide of how I approach myeloma therapy in a transplant eligible patient in 2018.

An unexpected cause of sacroiliitis in a patient with gout and chronic psoriasis with inflammatory arthritis: a case report.

BACKGROUND: Inflammatory back pain is a condition characterized by inflammation of the sacroiliac joints and lower spine. It is frequently seen in patients with spondyloarthropathies like ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis and reactive arthritis. Inflammatory back pain can be caused by many other conditions like infection and crystal deposition such as gout. In this case, it is difficult to specifically identify gout as a cause by ordinary imaging like magnetic resonance imaging (MRI) or ultrasound. CASE PRESENTATION: This case report describes a young man with severe psoriasis, presumptive psoriatic spondyloarthropathy and chronic extensive tophaceous gout which was difficult to treat because of non-compliance with medications and lifestyle. He presented with inflammatory type low back and buttocks pain with raised inflammatory markers. MRI of the lower back and sacroiliac joints showed features of active sacroiliitis. He was subsequently treated with a Tumor Necrosis Factor (TNF) alpha inhibitor for presumed axial psoriatic arthritis and had no significant benefit. Two attempts DECT of the lumbar spine was not executed correctly. CT lumbar spine and SIJs showed L2/3 endplate and left SIJ erosions mostly related to gout. Rasburicase was introduced. The tophi decreased in size peripherally with marginal improvement in back pain. From this study, we want to bring to the attention of physicians that gout can lead to back pain with inflammatory changes on MRI. We also want to address the importance of other imaging modalities if the cause of the back pain is not clear. CONCLUSION: This case is meant to highlight an important but overlooked cause of active sacroililitis and inflammatory type back pain in patients who have gout, and to bring to the attention that plain X-ray, MRI and ultrasound cannot differentiate between inflammatory sacroiliitis caused by seronegative arthritis versus gouty arthritis. CT scan can add more information but DECT is the preferred method for differentiation and identification of axial tophaceous gout.

Vitamin C is not the Missing Link Between Cigarette Smoking and Spinal Pain.

STUDY DESIGN: A nationwide cross-sectional study. OBJECTIVES: To measure the associations between cigarette smoking (defined as serum cotinine concentration >15 ng/mL) and the 3-month prevalence of spinal pain (neck pain, low back pain, low back pain with pain below knee, and self-reported diagnosis of arthritis/rheumatism) and related limitations, and to verify whether these associations are mediated by serum concentrations of vitamin C. SUMMARY OF BACKGROUND DATA: Cigarette smoking has been consistently associated with back pain, but this association has never been explained. Because vitamin C has recently been reported to be associated with spinal pain and related functional limitations, and the metabolism of vitamin C differs between smokers and nonsmokers, we hypothesized that the prevalence of spinal pain and related limitations might be greater among smokers because they are more susceptible to be in a state of hypovitaminosis C. METHODS: We conducted secondary analyses of National Health and Nutrition Examination Survey (NHANES) 2003 to 2004 data on 4438 individuals aged ≥20 years. RESULTS: Serum concentrations of vitamin C and cotinine were strongly and inversely correlated (r = -0.35, P < 0.0001). Smoking was statistically associated with the prevalence of neck pain [adjusted odds ratio: aOR: 1.25; 95% confidence interval (95% CI): 1.06-1.47], low back pain (aOR: 1.20; 95% CI: 1.04-1.39), and low back pain with pain below knee (aOR: 1.58; 95% CI: 1.13-2.22) and related limitations, with a dose-response relationship (P < 0.05). However, the associations between smoking and spinal pain were not mediated by concentrations of vitamin C. CONCLUSION: These results confirm the relationship between smoking and spinal pain, but they do not support a mediating effect of vitamin C on this relationship. LEVEL OF EVIDENCE: 2.

[A comparative study of immune and clinical indicators in radicular and myofascial back pain]. / Sravnitel'nyi analiz immunokhimicheskikh i klinicheskikh pokazatelei pri dorsalgiiakh koreshkovogo i reflektornogo geneza.

AIM: To compare immunochemical and clinical parameters in patients with chronic radicular and myofascial back pain. MATERIAL AND METHODS: A study included 92 patients (55 men and 37 women) with radicular pain syndrome and 97 patients (33 men and 64 women) with myofascial pain syndrome. Pain status was assessed with the differential visual analogous scale (at rest, on movement, at night and during spontaneous pain). Tensor algometry was used to measure pain intolerance thresholds at day and night. Levels of natural antibodies (nAB) to endogenous pain regulators (ß-endorphin, orphanin, serotonin, dopamine, histamine and angiotensin) were determined in the blood serum by ELISA. Patients were examined at admission to the hospital, on 10th and 21st days of treatment. RESULTS AND CONCLUSION: There was a significant decrease in pain syndrome in all patients to the 21st day. Pain intensity was higher in patients with radicular pain syndrome (р<0.05) in all functional states. Pain intolerance thresholds were initially reduced in both groups. No significant between-group differences in the dynamics were not found either in men or women. Women had lower pain intolerance thresholds compared to men. An analysis of nAB profiles to pain regulators showed that they were correlated with higher and high indices, with the predominance of nAB to ß-endorphin, orphanin and histamine in both groups. The increased levels of antibodies circulate in the blood serum of patients with dorsalgia for a long time can further be a factor of pain chronification.

Burst Spinal Cord Stimulation Increases Peripheral Antineuroinflammatory Interleukin 10 Levels in Failed Back Surgery Syndrome Patients With Predominant Back Pain.

OBJECTIVES: Burst spinal cord stimulation (SCS) has been reported to reduce back pain and improve functional capacity in Failed Back Surgery Syndrome (FBSS). However, its mechanism of action is not completely understood. Systemic circulating cytokines have been associated with the development of chronic back pain. METHODS: This prospective, feasibility study enrolled 12 refractory FBSS patients with predominant back pain (70% of overall pain) suitable for Burst SCS. Back and leg pain intensity (back pain [VASB ]/leg pain [VASL ]), functional capacity (sleep quality [PSQI]), depressive symptoms (BDI), body weight, stimulation parameters, and plasma levels of pro-inflammatory (Il-1b; TNF; HMGB1)/anti-inflammatory (Il-10) cytokines were collected at baseline and after three months of Burst SCS and compared to healthy controls. RESULTS: Pain intensity (pre VASB : 8.25 ± 0.75 vs. post 1.42 ± 1.24) and functional capacity (PSQI: pre 7.92 ± 3.92 vs. post 3.42 ± 1.24; BDI: pre 20.83 ± 3.56 vs. post 10.92 ± 0.75) significantly improved compared to baseline. Pro-inflammatory HMGB1 remained unchanged (preburst: 3.35 ± 3.25 vs. postburst: 3.78 ± 3.83 ng/mL; p = 0.27; W = -30) versus the HC group (2.53 ± 2.6 ng/mL; p = 0.47; U = 59), while anti-inflammatory IL-10 levels were significantly elevated after burst SCS as compared to baseline (preburst 12.54 ± 22.95 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48) and HC group (HC: 7.03 ± 11.6 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48; p = 0.04). Baseline preburst IL-10 values and preburst VASB significantly correlated (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while correlation was not significant between postburst IL-10 values and postburst VASB (Spearman correlation r = -0.49; p = 0.18; 95 CI -0.83 to -0.15). Postburst IL-10 values correlated significantly with postburst PSQI scores (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while no correlation was found between preburst and postburst changes related to the BDI. CONCLUSIONS: Burst SCS increased systemic circulating anti-inflammatory IL-10, improved FBSS back pain and back pain associated co-morbidities like disrupted sleep architecture and depressive symptoms in FBSS patients. Thus, suggesting a possible relationship between burst SCS and burst-evoked modulation of peripheral anti-inflammatory cytokine IL-10 in chronic back pain.

Serum vitamin C and spinal pain: a nationwide study.

Back pain brings about one of the heaviest burden of disease. Despite much research, this condition remains poorly understood, and effective treatments are frustratingly elusive. Thus, researchers in the field need to consider new hypotheses. Vitamin C (ascorbic acid) is an essential cofactor for collagen crosslinks, a key determinant of ligament, tendon, and bone quality. Recent studies have reported high frequency of hypovitaminosis C in the general population. We hypothesized that lack of vitamin C contributes to poor collagen properties and back pain. We conducted this study to examine the associations between serum concentration of vitamin C and the prevalence of spinal pain and related functional limitations in the adult general population. This study used nationwide cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004. Data were available for 4742 individuals aged ≥20 years. Suboptimal serum vitamin C concentrations were associated with the prevalence of neck pain (adjusted odds ratio [aOR]: 1.5; 95% confidence interval [CI]: 1.2-2.0), low back pain (aOR: 1.3; 95% CI: 1.0-1.6), and low back pain with pain below knee (aOR: 1.3; 95% CI: 1.0-1.9) in the past 3 months, self-reported diagnosis of arthritis/rheumatism (aOR: 1.4; 95% CI: 1.2-1.7), and related functional limitations' score (adjusted difference of means [aB]: 0.03; 95% CI: 0.00-0.05). The prevalence of hypovitaminosis C in the general population is high. Our study shows associations between vitamin C and spinal pain that warrant further investigation to determine the possible importance of vitamin C in the treatment of back pain patients.

Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders.

AIMS: To investigate the relationship between omentin-1 levels and painful temporomandibular disorders (TMD). METHODS: In a case-control design, chronic painful TMD cases (n = 90) and TMD-free controls (n = 54) were selected from participants in the multisite OPPERA study (Orofacial Pain: Prospective Evaluation and Risk Assessment). Painful TMD case status was determined by examination using established Research Diagnostic Criteria for TMD (RDC/TMD). Levels of omentin-1 in stored blood plasma samples were measured by using an enzyme linked immunosorbent assay. Binary logistic regression was used to calculate the odds ratios (ORs) and 95% confidence limits (CLs) for the association between omentin-1 and painful TMD. Models were adjusted for study site, age, sex, and body mass index. RESULTS: The unadjusted association between omentin-1 and chronic painful TMD was statistically nonsignificant (P = .072). Following adjustment for covariates, odds of TMD pain decreased 36% per standard deviation increase in circulating omentin-1 (adjusted OR = 0.64; 95% CL: 0.43, 0.96; P = .031). CONCLUSION: Circulating levels of omentin-1 were significantly lower in painful TMD cases than controls, suggesting that TMD pain is mediated by inflammatory pathways.

[Discussion of Routine Laboratory Data of a Patient Complaining of Back Pain and General Fatigue].

Conventional reversed clinicopathological conference (RCPC) is an educational method to interpret labora- tory data. In this RCPC, physicians and several specialists in laboratory medicine discussed laboratory data of a patient with tuberculous spondylitis who complained of back pain and general fatigue. Then, they and the moderators held a question-and-answer session with an audience in a hall, and they tried to understand the detailed state of the patient. This discussion revealed the usefulness of RCPC to elucidate the clinical state of patient. At the same time, we can understand the limits of laboratory data analysis. [Review].

The effect of smoking on clinical and radiographic variables, and acute phase reactants in patients with ankylosing spondylitis.

To investigate the association between smoking and clinical, inflammatory and radiographic parameters in patients with ankylosing spondylitis (AS). One hundred and six tumour necrosis factor inhibitor naïve patients with AS were included in the study. The erythrocyte sedimentation rate, C-reactive protein, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and modified Stroke AS Spine Score (mSASSS) were assessed cross-sectionally for each patient. Smoking history was obtained, and smoking pack years were calculated. Current smokers had significantly higher BASDAI (p < 0.001) and a trend for higher BASFI (p = 0.059). Ever smokers had significantly higher BASFI (p = 0.035) and a trend for higher mSASSS (p = 0.063) compared to never smokers. Pack years (smoking intensity) were positively correlated with duration of inflammatory back pain (r = 0.628, p < 0.001), BASFI (r = 0.443, p < 0.001) and mSASSS (r = 0.683, p < 0.001). Multivariate regression analyses showed that current smoking was independently associated with a higher BASDAI score [regression coefficient (B) = 14.75, p < 0.001] and increasing pack years were independently associated with higher mSASSS (B = 0.26, p = 0.005). In patients with AS, current smoking was strongly and independently associated with higher disease activity, and cumulative smoking exposure with more radiographic spinal damage. In AS smokers, smoking cessation should be strongly recommended.

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort.

OBJECTIVES: To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors. METHODS: The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls. RESULTS: Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10-9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels. CONCLUSIONS: DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.

A clinical and laboratory approach used to elucidate discordant results of high-sensitivity troponin T and troponin I.

BACKGROUND: Careful interpretation of discordant results in high-sensitivity troponin measurements is necessary in cases of suspect immunoassay interferences. We describe several procedures taken in a case of a polymorbid patient with chest pain, without clear evidence of myocardial necrosis and with increased high-sensitivity cardiac troponin T (hs-cTnT). We checked the Vafaie's algorithm for the evaluation of suspect interference in troponin measurements. METHODS: We conducted a case report analysis, additional measurements, a dilution test and pretreatment of plasma with blocking agents. RESULTS: Concentration of hs-cTnT (99 th percentile of "healthy" population 14 ng/L) increased from 120.1 ng/L to 280.4 ng/L during an 8-month period and decreased to 216.3 ng/L during the following month with repeatedly negative troponin I (TnI), hs-cTnI, myoglobin and creatine kinase MB (CK-MB). Suspected false positivity of hs-cTnT was further confirmed by treatment of plasma with an antiheterophile blocking agent (hs-cTnT before treatment 280.4 ng/L, after 16.53/16.23 ng/L). This outcome was further confirmed by the manufacturer's experiments. CONCLUSIONS: The false-positive results of hs-cTnT were caused by the presence of extremely rare high molecular weight protein, presumably IgM, most likely HAMA (human anti-mouse antibody). Only the pre-treatment of plasma with a blocking agent provided a reliable indication of the interference. Cooperation among clinicians, laboratory personnel and the manufacturer is essential.