Clinical significance of anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients.

BACKGROUND: Anti-mutated citrullinated vimentin (MCV) antibodies have recently been recommended as a better arthritis diagnostic marker. OBJECTIVES: To investigate the association between anti-MCV antibodies and the clinical, functional, and radiographic characteristics of rheumatoid arthritis (RA) patients. METHODS: This case-control study was conducted on 40 RA patients and 40 healthy subjects. All patients were subjected to an assessment of disease using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), function by HAQ-DI, physical activity by International Physical Activity Questionnaire (IPAQ), fatigue by Functional Assessment of Chronic Illness Therapy (FACIT), serological tests as well as anti-MCV Abs measurement. A plain X-ray of both hands and wrists was done. RESULTS: The anti-MCV Abs level was significantly higher in RA patients than in healthy controls (P< 0.001). The anti-MCV Abs had a significant positive correlation with DAS, CDAI, HAQ, RF, Anti-CCP, and CRP (P= 0.006, 0.013, 0.005, < 0.001, < 0.001and 0.041 respectively) and a significant negative correlation with FACIT (p= 0.007). Positive anti-MCV RA patients had significantly higher erosions, JSN, and a total sharp score. CONCLUSIONS: Anti-MCV Abs may contribute to poor physical activity and more fatigue in RA patients beyond their established role in disease activity and erosion.

The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.

BACKGROUND: There are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases. METHODS: A prospective study on 100 RA patients on MTX monotherapy was performed. Disease activity was measured at the start of treatment and 6 months after treatment with MTX. The patients were then split into two groups: those who responded to the treatment and those who did not. The molecular genetic study for the RFC1 (G80A) variant was employed via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique, the ATIC (C347G) variant was performed using TaqMan allelic discrimination real-time PCR, and the tandem repeat sequences of TYMS (2R/3R) were amplified by conventional PCR and detected by agarose gel electrophoresis. RESULTS: The genotype distribution of RFC-1 (G80A) showed significant variations among non-responders and responders in the recessive genetic model. A significant difference was found in TYMS (2R/3R) in the dominant and heterozygous genetic models. However, ATIC (C347G) genotype frequency did not exhibit substantial link with drug response in all genetic models. Furthermore, the genotype and allele rates of the analyzed variants did not show any significant association with adverse events in all genetic models. CONCLUSION: The 80AA genotype of RFC-1 G80A and the 2R/3R or 3R/3R genotypes of TYMS 2R/3R are more vulnerable to the good consequences of MTX therapy. Key Points • Current recommendations support the gold standard role of MTX as a first-line monotherapy for RA patients. However, up to 40% of RA patients do not respond or exhibit partial response to MTX. • Persistent disease activity due to treatment unresponsiveness will affect the long-term outcomes in RA patients. • We aimed, through molecular genetic study, to identify the connection between three variants in the folate pathway of MTX metabolism and the response to methotrexate monotherapy in a cohort of RA patients.

Axial Involvement in Psoriatic Arthritis: A Cross-sectional Clinical and Radiologic Studies.

OBJECTIVE: This study aimed to investigate spinal involvement in psoriatic arthritis (PsA) patients using clinical and radiographic methods. METHODS: A cross-sectional clinical study was conducted on 50 PsA patients diagnosed according to the CASPAR criteria. Clinical examinations and functional assessments were performed. A radiographic assessment of the spine was performed. RESULTS: Out of 50 PsA patients (mean age of 45.50 ± 9.90 years), (males and females constituted 27 (54.0%) and 23 (46.0%) respectively), 76% had radiological axial involvement; (26%) with inflammatory axial pain and (50%) without inflammatory axial pain (subclinical). Three axial radiographic patterns were detected including spondylitis without sacroiliitis (15.78%), spondylitis with sacroiliitis (78.94%), and sacroiliitis without spondylitis (5.26%). In axial PsA patients, males were more affected than females (χ2=11.679, p = 0.003), with older age (H = 15.817, p < 0.001) and higher body mass index (BMI) (F = 5.145, p = 0.010), increased psoriasis duration (H = 9.826, p = 0.007) and severity (Η=25.171, p < 0.001), and more spinal movement limitations than PsA patients without axial involvement (F = 26.568, p < 0.001). Cervical involvement was higher than lumbar involvement. Axial radiographic severity assessed by the PsA Spondylitis Radiology Index was associated with increased disability as assessed by the Health assessment questionnaire (rs = 0.533, p = 0.001) and decreased quality of life assessed by short form-36 score (rs = -0.321, p = 0.050). CONCLUSION: This study shows that a high percentage of PsA patients had axial involvement with a high percentage of them having asymptomatic radiological findings. The cervical spine is more frequently and severely affected than the lumbar spine. Axial PsA occurs in males more than females with characteristic older age and higher BMI, increased psoriasis duration, and more limitation of spinal mobility.

Cartilage and bone loss in premenopausal women with rheumatoid arthritis: Radiological and laboratory assessments.

INTRODUCTION: To investigate the radiological and laboratory features of bone and cartilage losses in premenopausal women with rheumatoid arthritis (RA). METHODS: This case-control study is the continuation of a study that was conducted on 48 women with RA and 48 matched healthy volunteers. All RA patients were previously subjected to clinical examination, disease activity assessment using the 28-joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI), serological tests, dual-energy X-ray absorptiometry measuring bone mineral density (BMD), and plain X-ray of both hands. Added to these, matrix metalloproteinase 3 (MMP-3) and cartilage oligomeric matrix protein (COMP) were measured by enzyme-linked immunosorbent assay. RESULTS: There were statistically significant differences between patients and controls regarding COMP and MMP-3, being higher in patients (p < .001). COMP and MMP-3 have significant positive correlation with serum levels of anti-cyclic citrullinated peptide (anti-CCP) and anti-carbamylated protein (anti-CarP). The original Sharp erosion score was positively correlated with the serum level of the studied antibodies and disease duration, but no significant correlation was found with either COMP, MMP-3, or DAS-28. Spine BMD and Z score were negatively correlated with disease activity and anti-CarP. There were significant positive relationhsips between indices of local cartilage and bone loss and the indices of systemic bone loss. MMP-3 had no correlation with indices of local cartilage and bone loss and disease activity scores. CONCLUSIONS: The pathogenic mechanism of hand joint damage involved the three studied autoantibodies namely, rheumatoid factor, anti-CCP and anti-CarP antibodies. Anti-CarP antibody was involved in the reduction of BMD of the spine. The association between systemic osteoporosis and hand joint damage pointed to a common pathogenic mechanism.

Association between AXIN1 gene polymorphism (rs9921222) of WNT signaling pathway and susceptibility to osteoporosis in Egyptian patients: a case-control study.

BACKGROUND: Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility. METHODS: A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk. RESULTS: We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03-136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23-31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7-110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6-36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001). CONCLUSION: AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP.

Differences between diaphragmatic compound muscle action potentials recorded from over the sternum and lateral chest wall in healthy subjects.

To report normative data for diaphragmatic compound muscle action potentials (DCMAPs) recorded from over the sternum and lateral chest wall (LCW) and highlight factors that may contribute to variations in DCMAP parameters at the two sites. The phrenic nerve of seventy-three healthy subjects was bilaterally stimulated at the posterior border of the sternocleidomastoid muscle. DCMAPs from over the sternum and LCW were recorded (inspiration/expiration). Normative values of sternal and LCW DCMAPs were presented. The mean values of latency of LCW DCMAPs, duration of sternal DCMAPs and area from both recording sites are close to values reported by other studies. The mean values of latency of sternal DCMAPs are higher than that reported by other studies. Significant differences were found between sternal and LCW potentials in the mean latency, amplitude, and area (p < 0.001). The duration did not differ between the two sites. Differences were found between inspiration and expiration, right and left sides, and men and women. Regression analysis showed a relation between latency of sternal and LCW potentials and age. Latency (LCW potentials) and amplitude and area (sternal/LCW potentials) were related to gender. Amplitude (LCW potentials/inspiration) and area (sternal potentials/inspiration) were related to chest circumference (p = 0.023 and 0.013 respectively). Area (sternal potentials/expiration) was related to the BMI (p = 0.019). Our normative values for sternal and LCW DCMAPs are provided. Notable differences in the DCMAPs parameters were detected between the two recording sites, inspiration and expiration, right and left, and men and women. The technique of phrenic nerve should be standardized.

A New Muscle Activation Dynamics Model, That Simulates the Calcium Kinetics and Incorporates the Role of Store-Operated Calcium Entry Channels, to Enhance the Electromyography-Driven Hill-Type Models.

Hill-type models are frequently used in biomechanical simulations. They are attractive for their low computational cost and close relation to commonly measured musculotendon parameters. Still, more attention is needed to improve the activation dynamics of the model specifically because of the nonlinearity observed in the electromyography (EMG)-force relation. Moreover, one of the important and practical questions regarding the assessment of the model's performance is how adequately can the model simulate any fundamental type of human movement without modifying model parameters for different tasks? This paper tries to answer this question by proposing a simple physiologically based activation dynamics model. The model describes the kinetics of the calcium dynamics while activating and deactivating the muscle contraction process. Hence, it allowed simulating the recently discovered role of store-operated calcium entry (SOCE) channels as immediate counterflux to calcium loss across the tubular system during excitation-contraction coupling. By comparing the ability to fit experimental data without readjusting the parameters, the proposed model has proven to have more steady performance than phenomenologically based models through different submaximal isometric contraction levels. This model indicates that more physiological insights are key for improving Hill-type model performance.

Anti-carbamylated protein antibodies in premenopausal rheumatoid arthritis women: relation to disease activity and bone loss.

OBJECTIVES: Anti-carbamylated protein antibodies (anti-CarP Abs) are present in patients with RA, however, their association with bone loss is not confirmed. The purpose of this study was to determine the relation between the serum level of anti-CarP Abs in premenopausal RA women and disease activity and bone loss. METHODS: This case-control study was conducted on 48 premenopausal women with RA and 48 matched healthy premenopausal women. All RA women were subjected to clinical examination, disease activity assessment using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), functional assessment using the HAQ, physical activity assessment using the International Physical Activity Questionnaire (IPAQ), fatigue assessment using the Modified Fatigue Impact Scale (MFIS), serological tests as well as anti-CarP Abs using ELISA. Moreover, the BMD was measured by DXA and plain X-ray of both hands was done to assess juxta-articular osteopenia and erosions. RESULTS: The anti-CarP Abs level was significantly higher in RA patients than in healthy controls. The serum level of anti-CarP Abs had a significant positive correlation with the RA DAS28, CDAI, HAQ, MFIS and original Sharp score, while a significant negative correlation was present with the IPAQ. Anti-CarP Abs were negatively correlated with either spine BMD or Z-score and positively correlated with the original Sharp score. CONCLUSION: Anti-CarP Abs were higher in premenopausal RA women compared with older and BMI matched healthy women. Anti-CarP Abs are associated with higher RA disease activity, increased disability and fatigability and decreased physical activity. Moreover, anti-CarP Abs are associated with systemic trabecular bone loss as well as local bone loss.

The Visual Analogue Scale Versus Numerical Rating Scale in Measuring Pain Severity and Predicting Disability in Low Back Pain.

BACKGROUND: Low back pain (LBP) is a public health problem that requires accurate assessment for proper management and predicting prognosis. OBJECTIVE: This study aims to assess the agreement between visual analogue scale (VAS) and numeric rating scale (NRS) in measuring LBP severity, and investigate their ability in predicting disability. METHODS: A cross-sectional study was performed on 100 patients with chronic LBP. Pain severity assessment was performed using VAS, NRS, and pain severity scores of the Brief Pain Inventory (BPI). Disability assessment was done by BPI-Pain interference and Modified Oswestry Disability Index (MODI). RESULTS: There was a significant positive correlation between VAS and NRS (r = 0.92, p < 0.001) with high agreement between both as detected by Bland-Altman method (mean difference = 0.33). Moreover, there was significant (p < 0.001) positive correlation between disability scores and either VAS (r = 0.92 with BPI pain interference; r = 0.75 with MODI) or NRS (r = 0.95 with BPI pain interference; r = 0.68 with MODI). By using receiver operating characteristic curve, a score of 6 in VAS or NRS can predict severe disability, whereas VAS score higher than 4 and NRS score higher than 3 can predict moderate disability. CONCLUSIONS: Visual analogue scale and NRS appeared reliable in assessing LBP severity with no significant difference between them. Moreover, either VAS or NRS scores can predict disability of patients with LBP.

Efficacy of pregabalin as a monotherapy versus combined pregabalin and milnacipran in the management of fibromyalgia.

AIM: To compare the efficacy and tolerability of combined pregabalin (PGB) and milnacipran (MLN) in female patients with fibromyalgia (FM) versus PGB as a monotherapy. METHODS: The present randomized open study included 58 female patients diagnosed with FM (registered on 4/2/19: NCT03905486). Patients were randomly divided into 2 groups (2:2); group 1 included 29 patients who received PGB monotherapy (150 mg twice daily) and group 2 included 29 patients who received combined PGB (150 mg twice daily) and MLN (50 mg twice daily) for 3 months. At the initial visit, patients were subjected to demographic data collection and assessed by the visual analog scale (VAS) for pain and the FM impact questionnaire (FIQ). Outcome measures after 3 months: FIQ, VAS and Leeds Sleep Evaluation Questionnaire. RESULTS: The median disease duration was 2 years in group 1 (6 months to 5 years) and 2 years in group 2 (6 months to 12 years). The dropout rate was 20.7% in group 1 (n = 6) and 10.3% in group 2 (n = 3). At the follow-up evaluation, a statistically significant improvement was observed in VAS and FIQ scores in both groups (P < 0.001). Although the percentage of patients demonstrating significant improvement in pain, disease impact and sleep pattern were higher in group 2, this did not reach statistical significance. CONCLUSION: Although PGB as a monotherapy and in combination with MLN have both shown adequate efficacy in the treatment of patients with FM, the combined therapy did not demonstrate superiority over the monotherapy.

Serum Peptidomic Profile as a Novel Biomarker for Rheumatoid Arthritis.

Over the last decades, there has been an increasing need to discover new diagnostic RA biomarkers, other than the current serologic biomarkers, which can assist early diagnosis and response to treatment. The purpose of this study was to analyze the serum peptidomic profile in patients with rheumatoid arthritis (RA) by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The study included 35 patients with rheumatoid arthritis (RA), 35 patients with primary osteoarthritis (OA) as the disease control (DC), and 35 healthy controls (HC). All participants were subjected to serum peptidomic profile analysis using magnetic bead (MB) separation (MALDI-TOF-MS). The trial showed 113 peaks that discriminated RA from OA and 101 peaks that discriminated RA from HC. Moreover, 95 peaks were identified and discriminated OA from HC; 38 were significant (p < 0.05) and 57 nonsignificant. The genetic algorithm (GA) model showed the best sensitivity and specificity in the three trials (RA versus HC, OA versus HC, and RA versus OA). The present data suggested that the peptidomic pattern is of value for differentiating individuals with RA from OA and healthy controls. We concluded that MALDI-TOF-MS combined with MB is an effective technique to identify novel serum protein biomarkers related to RA.

Diaphragmatic motor cortex hyperexcitability in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVES: Respiratory muscles dysfunction has been reported in COPD. Transcranial magnetic stimulation (TMS) has been used for assessing the respiratory corticospinal pathways particularly of diaphragm. We aimed to study the cortico-diaphragmatic motor system changes in COPD using TMS and to correlate the findings with the pulmonary function. METHODS: A case control study recruited 30 stable COPD from the out-patient respiratory clinic of Main Alexandria University hospital- Egypt and 17 healthy control subjects who were subjected to spirometry. Cortical conduction of the diaphragm was performed by TMS to all participants followed by cervical magnetic stimulation of the phrenic nerve roots. Diaphragmatic resting motor threshold (DRMT), cortical motor evoked potential latency (CMEPL), CMEP amplitude (CMEPA), peripheral motor evoked potential latency (PMEPL), PMEP amplitude (PMEPA) and central motor conduction time (CMCT) were measured. RESULTS: 66.7% of COPD patients had severe and very severe COPD with median age of 59 (55-63) years. There was statistically significant bilateral decrease in DRMT, CMEPA and PMEPA in COPD group versus healthy subjects and significant increase in CMEPL and PMEPL (p <0.01). Left CMCT was significantly prolonged in COPD group versus healthy subjects (p <0.0001) but not right CMCT. Further, there was significant increase in CMEPL and CMCT of left versus right diaphragm in COPD group (p = 0.003 and 0.001 respectively) that inversely correlated with FEV1% and FVC% predicted. Right and left DRMT were insignificantly different in COPD group (p >0.05) but positively correlated with FEV1/FVC, FEV1% and FVC% predicted. CONCLUSION: Central cortico-diaphragmatic motor system is affected in COPD patients with heterogeneity of both sides that is correlated with pulmonary function. SIGNIFICANCE: Coticospinal pathway affection could be a factor for development of diaphragmatic dysfunction in COPD patients accordingly its evaluation could help in personalization of COPD management especially pulmonary rehabilitation programs.