High Baseline Neutrophil-to-Lymphocyte Ratio Could Serve as a Biomarker for Tumor Necrosis Factor-Alpha Blockers and Their Discontinuation in Patients with Ankylosing Spondylitis.

BACKGROUND: This study explores the association of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios with the 3-month treatment response and persistence of tumor necrosis factor-alpha (TNF-α) blockers in patients with ankylosing spondylitis (AS). METHODS: This retrospective cohort study investigated 279 AS patients who were newly initiated on TNF-α blockers between April 2004 and October 2019 and 171 sex- and age-matched healthy controls. Response to TNF-α blockers was defined as a reduction in the Bath AS Disease Activity Index of ≥50% or 20 mm, and persistence referred to the time interval from the initiation to discontinuation of TNF-α blockers. RESULTS: Patients with AS had significantly increased NLR, MLR, and PLR ratios as compared to controls. The frequency of non-response at 3 months was 3.7%, and TNF-α blockers' discontinuation occurred in 113 (40.5%) patients during the follow-up period. A high baseline NLR but not high baseline MLR and PLR showed an independently significant association with a higher risk of non-response at 3 months (OR = 12.3, p = 0.025) and non-persistence with TNF-α blockers (HR = 1.66, p = 0.01). CONCLUSIONS: NLR may be a potential marker for predicting the clinical response and persistence of TNF-α blockers in AS patients.

Diagnostic Value of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Monocyte-to-Lymphocyte Ratios for the Assessment of Rheumatoid Arthritis in Patients with Undifferentiated Inflammatory Arthritis.

Background: To investigate the diagnostic performance of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in the diagnosis of rheumatoid arthritis (RA) in subjects with undifferentiated inflammatory arthritis (UIA). Methods: This retrospective cohort study investigated 201 female patients with UIA (≥1 swollen joint) and 280 age-matched, healthy female controls. "Clinical RA" was defined based on the clinical judgment of a rheumatologist and "disease-modifying anti-rheumatic drugs (DMARDs) RA" was defined as a case of initiating DMARDs treatment within 6 months after the first visit. "Classified RA" was defined as fulfilling the 2010 classification criteria for RA. Receiver operating characteristics were used to determine the optimal cut-off value. Results: UIA patients had a significantly higher NLR, PLR, and MLR than the controls. Among the 201 UIA patients, 65 (32.3%), 63 (31.3%), and 61 (30.3%) subjects were classified as clinical RA, DMARDs RA, and classified RA, respectively. At a cut-off of 0.24, MLR showed moderate accuracy for the diagnosis of DMARDs RA (sensitivity, 65.1%; specificity, 62.3%; area under the curve [AUC], 0.701; p < 0.001). However, the diagnostic accuracies of NLR and PLR were low. Conclusions: MLR may be used as a complementary diagnostic indicator for RA diagnosis in patients with UIA.

Associations of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio with Osteoporosis and Incident Vertebral Fracture in Postmenopausal Women with Rheumatoid Arthritis: A Single-Center Retrospective Cohort Study.

Background and Objectives: We investigated whether nutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphoycte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are associated with the presence of osteoporosis (OP) and vertebral fractures in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included 413 postmenopausal patients with RA and 200 healthy controls who underwent dual-energy X-ray absorptiometry (DEXA) between January 2005 and December 2017. DEXA examination data were defined as the index date, and all laboratory values were measured within one month from the index date. OP was defined as a T-score < −2.5, and incident vertebral fractures were defined as the first occurrence of non-traumatic fractures after the index date. NLR, PLR, and MLR measures were dichotomized by a median split (low vs. high). Results: The median NLR, PLR, and MLR in RA patients were significantly higher than those in controls. The frequencies of OP of the lumbar spine, hip, and either site in postmenopausal patients with RA were 24.7%, 15.5%, and 32%, respectively, and were significantly higher than those in controls. After adjusting for confounding factors, a high baseline NLR was significantly associated with OP at either site (OR = 1.61, p = 0.041). In addition, high baseline NLR (OR = 2.11, p = 0.025) and PLR (OR = 2.3, p = 0.011) were related with the presence OP at hip. During the follow-up period, 53 (12.8%) patients with RA developed vertebral fractures incidentally. In multivariable Cox regression models, a high baseline NLR (HR = 4.72, p < 0.001), PLR (HR = 1.96, p = 0.024), and MLR (HR = 2.64, p = 0.002) were independently associated with a higher risk of incidental vertebral fractures. Conclusions: Our data suggest that NLR, PLR, and MLR can be used as potential markers of systemic bone loss among individuals with RA.

Status of Glucocorticoid-Induced Osteoporosis Preventive Care in Korea: A Retrospective Cohort Study on the Korean National Health Insurance Service Database.

Background and Objectives: It is crucial to prevent osteoporosis in patients receiving long-term glucocorticoid (GC) treatment. This study aimed to investigate the frequency and associated factors of preventive care for glucocorticoid-induced osteoporosis (GIOP) in Korea. Materials and Methods: Using the Korean National Health Insurance Service database, we identified 37,133 individuals aged ≥ 20 years who commenced long-term (≥90 days) oral GC between 2011 and 2012. High-quality GIOP preventive care was defined as either a bone mineral density (BMD) test, calcium and/or vitamin D supplementation, or prescription osteoporosis medications within 6 months of GC initiation. Multivariable logistic regression models were used to calculate odds ratios (ORs) for associated factors for high-quality GIOP preventive care. Results: The mean age was 49.8 years, and 18,476 (49.8%) patients were female. The frequency of high-quality GIOP preventive care was only 3.68% (BMD test, 1.46%; osteoporosis medications, 1.65%; calcium/vitamin D, 1.63%). Increasing age (OR = 2.53, p < 0.001; 40-49 years, OR = 3.99, p < 0.001; 50-59 years, OR = 5.17, p < 0.001; 60-69 years, OR = 8.07, p < 0.001; ≥70 years, respectively), systemic autoimmune disease (OR = 3.08, p < 0.001), rural residence (OR = 1.19, p = 0.046), concomitant hyperthyroidism (OR = 1.58, p = 0.007), and malignancy (OR = 1.59, p < 0.001) were significantly associated with a higher likelihood of receiving high-quality GIOP preventive care. Male sex (OR = 0.26, p < 0.001) and GC prescription in primary care clinics and nursing hospitals (OR = 0.66, p < 0.001) were associated with a lower rate of high-quality GIOP preventive care. Conclusions: Most Korean patients treated with GC did not receive appropriate preventive care for GIOP in real-world practice. More efforts are needed by clinicians to prevent, screen, and treat GIOP.

Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the potential role of mirodenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, in the treatment of fibrosis in SSc. We used a bleomycin (BLM)-induced SSc mouse model to mimic the typical features of fibrosis in human SSc and examined the dermal thickness to assess the degree of skin fibrosis after staining with hematoxylin and eosin or Masson's trichrome stains. The effect of mirodenafil on the expression of profibrotic genes was also analyzed by treating fibroblasts with transforming growth factor (TGF)-ß and mirodenafil. We showed that mirodenafil ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α-SMA in the BLM-induced SSc mouse model. Further, using mouse embryonic fibroblasts and human lung fibroblasts, we demonstrated that the expression of collagen and profibrotic genes was reduced by treatment with mirodenafil. Finally, we showed that mirodenafil inhibited TGF-ß-induced phosphorylation of Smad2/3 in fibroblasts, which suggested that this drug may ameliorate fibrosis by suppressing the TGF-ß/Smad signaling pathway. Our findings suggest that mirodenafil possesses a therapeutic potential for treating fibrosis in SSc.

Bath Ankylosing Spondylitis Disease Activity Index is Associated With the Quality of Sleep in Ankylosing Spondylitis Patients.

Objective: High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep. Methods: A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates. Results: Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI>5) There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023). Conclusion: BASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS.

Measurement of Coracohumeral Distance in 3 Shoulder Positions Using Dynamic Ultrasonography: Correlation With Subscapularis Tear.

PURPOSE: To detect differences between the values of dynamic coracohumeral distance (CHD) measured using ultrasonography (USG) in different shoulder rotations and to investigate its correlation with subscapularis tear. METHODS: We prospectively enrolled consecutive patients (n = 168) who were scheduled to have arthroscopic rotator cuff repair. Patients with a history of previous shoulder surgery or shoulder fracture and patients with external rotation less than 30° were excluded from the study. Dynamic CHD was measured using USG in 3 different shoulder positions: external rotation, neutral and internal rotation. We evaluated the intrarater reliability with 3 times repetition of measurement. Patients were divided into 1 of 3 groups according to arthroscopic findings: intact subscapularis, partial-thickness tear, and full-thickness tear of the subscapularis. The control group (n = 23) included patients without rotator cuff tears from the outpatient clinic. Subgroup analysis-according to the presence of dynamic subcoracoid stenosis, defined as a CHD less than 6 mm measured in internal rotation-was performed to find the clinical effect of dynamic subcoracoid stenosis. RESULTS: A partial-thickness tear of the subscapularis tendon was present in 60 patients (35.7%) and a full-thickness tear in 26 patients (15.4%) among 168 patients. The CHD was maximum in external rotation and the narrowest in internal rotation. There were no statistical differences in the CHDs between groups with different subscapularis tear status. According to the presence of dynamic subcoracoid stenosis, patients with dynamic subcoracoid stenosis had a significantly higher incidence of partial-thickness subscapularis tear than those without stenosis (P = .022). CONCLUSIONS: The CHD values were narrowest in shoulder internal rotation, which is thought to be the pathogenic position. We could not confirm the correlation between CHD and subscapularis tear. However, patients who have dynamic subcoracoid stenosis had significantly higher incidence of subscapularis tear than others without dynamic stenosis. LEVEL OF EVIDENCE: Level II, prospective prognostic cohort study.

Measurement of volumetric bone mineral density in proximal humerus using quantitative computed tomography in patients with unilateral rotator cuff tear.

BACKGROUND: The first purpose of this study was to reveal the clinically important region-specific volumetric bone mineral density (vBMD) of the proximal humerus in patients with unilateral rotator cuff tear (RCT), and the second was to evaluate the relationship between vBMD of the proximal humerus and BMD of the hip and lumbar spine measured using conventional dual-energy X-ray absorptiometry. Finally, we assessed whether any clinical factor could predict local osteoporosis of the proximal humerus. METHODS: The study enrolled 65 patients who underwent arthroscopic repair of a unilateral RCT between April 2010 and July 2011 and had computed tomography scans of bilateral proximal humeri. Considering the suture bridge technique for RCT repair to be the leading treatment, region-specific BMD was measured in 7 volumetric blocks in the proximal humerus. Image and quantification processing was used to calculate the vBMD of each block. RESULTS: The vBMD values in all 7 blocks of the symptomatic shoulder were significantly lower than those of the asymptomatic contralateral shoulder (P < .05). Regardless of RCT, the greater tuberosity showed significant location-dependence in vBMD value; that is, the vBMD value was the highest in the posterolateral portion and the lowest in the medial portions. No significant correlation was found between vBMD of the greater tuberosity and clinical factors except female gender. CONCLUSION: The present study demonstrated the regional and bilateral differences in vBMD within the greater tuberosity in patients with unilateral RCT. Aside from female gender, no other clinical factors presented as risk factors for a higher possibility of osteoporosis.

Effect of platelet-rich plasma and porcine dermal collagen graft augmentation for rotator cuff healing in a rabbit model.

BACKGROUND: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. PURPOSE: To verify the effect of platelet-rich plasma (PRP) with and without porcine dermal collagen graft augmentation on tendon-to-bone healing, using the rabbit supraspinatus tendon. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 80 rabbits were randomly allocated into 4 groups (20 rabbits per group: 12 for histological and 8 for mechanical testing): repair (R), repair + patch augmentation (RPa), repair + PRP (RPr), and repair + patch + PRP (RPaPr). The right shoulder was used for experimental interventions, and the left served as a control. Six weeks after the detachment of the supraspinatus, the torn tendon was repaired in a transosseous manner, simulating double-row repair in all groups. Platelet-rich plasma was prepared and applied onto the repair site in the RPr and RPaPr groups, and the patch was used to augment the repair in the RPa and RPaPr groups. The mechanical tensile strength test was performed at 8 weeks after repair and the histological evaluation at 4 and 8 weeks. RESULTS: At 4 weeks, the collagen fibers were poorly organized, and fiber continuity was not established in all groups. However, vascularity and cellularity were higher with granulation tissue formation in the PRP-treated groups (RPr and RPaPr) than the nontreated groups (R and RPa). At 8 weeks, tendon-to-bone integration was much improved with more collagen fibers, and longitudinally oriented collagen fibers were visible in all groups. The PRP-treated groups showed better collagen fiber continuity and orientation than the nontreated groups; however, no distinctive difference was found between the patch-augmented groups (RPa and RPaPr) and nonaugmented groups (R and RPr). The mean load-to-failure results were 61.57 ± 29.99 N, 76.84 ± 16.08 N, 105.35 ± 33.82 N, and 117.93 ± 12.60 N for the R, RPa, RPr, and RPaPr groups, respectively, and they were significantly different between the R and RPr (P = .018), R and RPaPr (P = .002), and RPa and RPaPr (P = .029) groups. CONCLUSION: This animal study showed the enhancement of tendon-to-bone healing after local administration of autologous PRP assessed by histological and biomechanical testing in a rabbit model of chronic rotator cuff tears. However, there was little additive effect of the patch graft. CLINICAL RELEVANCE: The use of PRP might be a biological supplement to increase the rotator cuff healing rate, which still remains low even after successful cuff repair, but this result should be interpreted with caution regarding clinical applications.

A prospective consecutive study of instrumented posterolateral lumbar fusion using synthetic hydroxyapatite (Bongros-HA) as a bone graft extender.

A prospective, single institution, clinical case-matched, radiographic study was undertaken. Thirty-two patients underwent posterior lumbar interbody fusion with cages containing laminectomized bone chips and posterolateral lumbar fusion with pedicle screws. Autogenous bone graft (3 mL) plus 3 mL of hydroxyapatite was placed in one side of a posterolateral gutter, and 6 mL of autogenous iliac bone graft was placed on the other side. Bony union, volumes of fusion mass, and bone absorption rates were postoperatively evaluated using simple radiographs and 3D-CT scans. Average postoperative Lenke scores at 3 and 6 months in the hydroxyapatite group were statistically higher than in the autograft group, but at 12 months no difference was found between the hydroxyapatite and autograft groups in terms of fusion rate. Complete fusion rates by 3D-CT were 86.7% in the hydroxyapatite group and 88.9% in the autograft group, which are not significantly different. Volumes of fusion mass and bone absorption rates at 12 months were 2.35 mL in the hydroxyapatite group and 1.31 mL in the autograft group. The mean fusion mass volume was greater in the hydroxyapatite group than in the autograft group. Lumbar posterolateral fusion using a mixture of hydroxyapatite artificial bone and autogenous bone graft showed good bony union similar to that shown with autogenous bone only. This study suggests that hydroxyapatite bone chips could be used usefully as a bone-graft extender in short-segment posterolateral spinal fusion.