Unchanged incidence of major adverse events amidst rising surgical interventions for osteoporotic vertebral fractures, 2015-2021.

This study investigated treatment trends and major adverse events in patients hospitalized for osteoporotic vertebral fracture (OVF). The frequency of surgical interventions for OVF increased significantly, but this did not decrease major adverse events. The findings underscore the necessity for reevaluating OVF management strategies. PURPOSE: Osteoporotic vertebral fracture (OVF) is a common condition in the aging population, often leading to increased morbidity and mortality. Here, we analyzed treatment trends and incidence of major adverse events in patients hospitalized for OVF. METHODS: We conducted a cross-sectional descriptive study, using a large Japanese hospital administrative database. The cohort included hospitalized patients aged 65 years or older, admitted for OVF from January 2015 to December 2021. The primary outcomes were the trend in the proportion of the patients undergoing surgery for OVF and the incidence of major adverse events within 30 days of admission. As a secondary outcome, we evaluated the trend in hospitalization costs. RESULTS: The study cohort consisted of 14,714 patients, with a mean age of 82.4 years. There was a significant increase in surgical interventions for OVF, from 3.7% of patients in 2015 to 9.8% in 2021 (p < 0.001). The incidence of major adverse events remained unchanged, with a risk ratio of 1.09 (95% confidence interval, 0.88 to 1.35) in 2021 compared to 2015. Average hospitalization costs increased significantly, from $7,570.6 (SD 6,047.0) in 2015 to $9,502.9 (SD 7,231.5) in 2021 (p < 0.001). CONCLUSION: Despite a significant increase in the proportion of surgical intervention for OVF, no reduction in the risk of major adverse events was observed between 2015 and 2021. Surgeons and policy makers need to interpret these findings and work towards an optimized approach to the management of OVF in the aging population.

Effects of IL-6, JAK, TNF inhibitors, and CTLA4-Ig on knee symptoms in patients with rheumatoid arthritis.

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.

Risk factors for preoperative neurological impairment in patients with spinal meningioma: A retrospective multicenter study.

BACKGROUND: Patients with spinal meningioma may present preoperatively with paralysis and sensory deficits. However, there is a paucity of detailed evaluations and a lack of consensus regarding imaging findings that are predictive of neurological symptoms in patients with spinal meningioma. METHODS: Herein, a total of 55 patients who underwent surgical resection of spinal meningiomas in eight hospitals between 2011 and 2021 were enrolled. Patient characteristics, degree of muscle weakness, sensory disturbances, and the presence of bowel/bladder dysfunction (BBD) before surgical treatment were evaluated using medical records. Patients with American Spinal Injury Impairment Scale grades A-C and the presence of BBD were classified into the paralysis (+) group. Patients with sensory disturbances were assigned to the sensory disturbance (+) group. Based on magnetic resonance (MR) and computed tomography images, the tumor location was classified according to the spinal level and its attachment to the dura mater. To evaluate tumor size, the tumor occupation ratio (OR) was calculated using the area and distance measurement method in horizontal MR images, and the maximum length and area of the tumor in the sagittal plane were measured. RESULTS: Of all patients, 85 % were women. The mean age of patients at surgery was 69.7 years. Twenty-eight (51 %) and 41 (75 %) patients were classified into the paralysis (+) and sensory disturbance (+) groups, respectively. The average tumor length and area in the sagittal plane were 19.6 mm and 203 mm2, respectively; OR-area and diameters were 70.3 % and 72.3 %, respectively. In univariate analyses, tumor length and area in the sagittal plane were significant risk factors for paralysis. OR-diameter, symptom duration, and a low MIB-1 index correlated with sensory disturbances. Multivariate logistic regression analysis demonstrated that the area and length of the tumor in the sagittal plane were significantly correlated with paralysis, whereas the OR-diameter and symptom duration significantly correlated with sensory disturbances. The cut-off values for the area and length of the tumor in the sagittal plane to predict paralysis were 243 mm2 and 20.1 mm, respectively. CONCLUSIONS: Preoperative paralysis in patients with spinal meningiomas was significantly associated with sagittal tumor size than with high tumor occupancy in the horizontal plane. Sensory disturbances were associated with high occupancy in the horizontal plane. Patients with spinal meningiomas > 20 mm in length or 243 mm2 in area in the sagittal plane are at risk of developing paralysis and could be considered for surgery even in the absence of paralysis.

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study.

Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort). We assessed the drug retention rates of b/targeted synthetic DMARDs with different modes of action (tumour necrosis factor inhibitors (TNFis), immunoglobulins fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), interleukin-6 receptor inhibitors (IL-6Ris), and JAKis) in patients with RA stratified by pre-treatment estimated glomerular filtration rate (eGFR) levels. The time to discontinuation of bDMARDs or JAKis was analysed using a multivariate Cox proportional hazards model This study included 3775 patients, who were classified into three groups (the normal group (eGFR ≥ 60 mL/min/1.73 m2): 2893 patients; CKDa group (eGFR 45-60 mL/min/1.73 m2): 551; and CKDb group (eGFR < 45 mL/min/1.73 m2): 331). In the CKDb group, the 12-month drug retention rate due to adverse events (AE) was the lowest in patients treated with JAKi (TNFi: 93.1%; IL-6Ri: 94.1%; CTLA-4-Ig: 92.3%; JAKi: 75.1%). In the normal and CKDa groups, drug retention rates due to AE were similar among patients treated with bDMARDs and JAKi. In contrast, drug retention rates due to inefficacy were similar between bDMARDs and JAKis in all groups. In the Cox-proportional model, in the CKDb group, TNFi, IL-6Ri, and CTLA-4-Ig showed lower incidence of drug discontinuation due to AE than JAKis (TNFi: hazard ratio = 0.23 (95% confidence interval 0.09-0.61), IL-6Ri: 0.34 (0.14-0.81), CTLA-4-Ig: 0.36 (0.15-0.89)). JAKis showed the lowest drug retention due to AE in patients with moderate-to-severe and severe renal impairment (eGFR < 45 mL/min/1.73 m2). Physicians should pay more attention to renal function when using JAKis than when using bDMARDs.

Active Rheumatoid Arthritis and Scoliosis: A Mid-Term Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To elucidate the factors related to progression of scoliosis in patients with rheumatoid arthritis (RA) using longitudinal cohort data. SUMMARY OF BACKGROUND DATA: Thirty percent of patients with RA have lumbar scoliosis. However, the effectiveness of current treatment methods in preventing the progression of scoliosis is not well-understood due to a lack of longitudinal studies. METHODS: We enrolled 180 patients with RA who were followed up for over two years, all of whom underwent standing spinal X-rays. These patients were categorized based on their disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) into two groups: those in remission (n=76) and those in non-remission (n=104). We evaluated various radiographic measures, including C7 center sacral vertical line (C7-CSVL), pelvic obliquity, major Cobb angle, and curve location. RESULTS: Fifty-three (29.4%) patients presented progression of scoliosis during a mean follow-up period of 4.8 years. Patients in the non-remission showed larger Cobb angle at baseline and final follow-up, compared to those in remission. The annual progression rate of the curve was also greater in the non-remission group (1.04 degree /year), than in the remission group (0.59 degree /year, P=0.001). There was no difference in the incidence of new vertebral fractures. The presence of a baseline cobb angle of 10 degree or more (OR: 3.14; 95% CI: 1.38-7.13; P=0.006), glucocorticoid use (OR: 2.88; 95% CI: 1.18-7.06; P=0.021), and non-remission at baseline (OR: 2.83; 95% CI: 1.25-6.41; P=0.012) were significant risk factors for progression of scoliosis. CONCLUSION: RA disease activity is linked to progression of scoliosis in patients with RA. Patients with RA who present with an initial scoliosis of 10 degrees or greater, require glucocorticoids for treatment and are in non-remission at baseline may be at high risk for scoliosis progression.

Energy landscape analysis and time-series clustering analysis of patient state multistability related to rheumatoid arthritis drug treatment: The KURAMA cohort study.

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.

Sagittal Section Hounsfield Units of the Upper Instrumented Vertebrae as a Predictor of Proximal Junctional Vertebral Fractures Following Adult Spinal Deformity Surgery.

STUDY DESIGN: A retrospective observational study. PURPOSE: This study aimed to determine an accurate and convenient screening method for predicting proximal junctional fractures (PJFr) following surgery for adult spinal deformity (ASD) using computed tomography (CT)-based measurement of Hounsfield units (HUs). OVERVIEW OF LITERATURE: CT-based measurement of HUs is an alternative tool for assessing bone mineral density. However, the optimal method for predicting adjacent vertebral fractures following spinal fusion using HUs remains unclear. METHODS: This retrospective observational study included 42 patients who underwent reconstructive surgery for ASD. Elliptical regions of interest (ROIs) on the axial section and rectangular ROIs on the sagittal section were placed at the upper instrumented vertebrae (UIV), UIV+1, and UIV+2. In addition, the HU value of the L2 vertebra was used as the representative. RESULTS: PJFr occurred in 28.6% of patients within 2 years following surgery. The HU values obtained from the axial sections of L2, UIV, UIV+1, and UIV+2 were not significantly associated with the incidence of PJFr within 2 years, except for the ROI set in the lower region of the L2 vertebra. However, the HU value of the anterior third of the UIV in the sagittal section was significantly lower in the PJFr group than in the nonPJFr group (87.0 vs. 160.3, p =0.001). A UIV HU value of <100 was associated with a higher incidence of PJFr than an HU vaue of >100 (p <0.05). CONCLUSIONS: Measurements of HU in the anterior one-third of the UIV in the sagittal section demonstrated predictive ability for PJFr following ASD surgery. A UIV HU value of <100 emerged as a risk factor for PJFr.

Low Hounsfield unit values on computed tomography as a potential predictor of vertebral fracture in patients with rheumatoid arthritis: The KURAMA cohort study.

OBJECTIVE: Hounsfield units (HU) measured using computed tomography (CT) have gained considerable attention for the detection of osteoporosis. This study aimed to investigate whether opportunistic CT could predict vertebral fractures in patients with rheumatoid arthritis (RA). METHODS: A total of 233 patients with RA who underwent chest CT were included in this study. The HU values of the anterior 1/3 of the vertebral bodies based on the sagittal plane at T11-L2 after reconstruction were measured. The incidence of vertebral fractures was investigated with respect to the HU value. RESULTS: Vertebral fractures were identified in 32 patients during a mean follow-up period of 3.8 years. In patients who experienced vertebral fractures within 2 years of CT imaging, the HU values of the vertebral bodies (T11-L2) were lower than those in patients who did not experience fractures. Receiver operating characteristic curve analysis identified that a T11 HU value of <125 was a risk factor for vertebral fracture within 2 years. Multivariate analysis showed that a T11 HU value of <125 and the existence of prevalent vertebral fractures were significant risk factors for fracture. CONCLUSION: HU measurements of the anterior 1/3 of the vertebral body are a potential predictor for vertebral fractures in patients with RA.

Effect of high disease activity on spinal sagittal malalignment in patients with rheumatoid arthritis.

OBJECTIVE: Atlantoaxial subluxation is a well-known serious complication encountered in patients with rheumatoid arthritis (RA). However, it is unknown whether RA affects global spinal alignment. The aim of this study was to investigate whether high disease activity in patients with RA exacerbates spinal sagittal malalignment. METHODS: The authors included 197 patients with RA who were followed up for > 2 years; standing spinal radiographs were obtained in all patients. Patients were divided into persistent moderate disease activity/high disease activity (pMDA/HDA; n = 64) and non-pMDA/HDA (n = 133) groups based on the disease activity at follow-up visits. Radiographic parameters assessed included pelvic incidence, pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and C7 sagittal vertical axis (SVA). RESULTS: Over an average 5-year follow-up, increases in SVA, PT, and TK and a decrease in LL were observed. The pMDA/HDA group had a larger increase in PT and a higher incidence of vertebral fractures than the non-pMDA/HDA group. After adjusting variables using propensity score matching, the authors still found a higher rate of increase in PT (0.79°/year vs 0.01°/year, p = 0.001) in the pMDA/HDA group than in the non-pMDA/HDA group. This trend remained consistent even when patients who developed vertebral fractures were excluded. CONCLUSIONS: Spinal sagittal alignment deteriorates over time in patients with RA. High disease activity in RA exacerbates spinal deformity.

Pressure Dynamics on Intervertebral Disc Cages in Transforaminal Lumbar Interbody Fusion: A Cadaver Study.

OBJECTIVE: This study aimed to quantify the change in pressure on the cage during compression manipulation in lumbar interbody fusion. While the procedure involves applying compression between pedicle screws to press the cage against the endplate, the exact compression force remains elusive. We hypothesize that an intact facet joint might serve as a fulcrum, potentially reducing cage pressure. METHODS: Pressure on the intervertebral disc cage was measured during compression manipulation in 4 donor cadavers undergoing lumbar interbody fusion. Unilateral facetectomy models with both normal and parallel compression and bilateral facetectomy models were included. A transforaminal lumbar interbody fusion cage with a built-in load cell measured the compression force. RESULTS: Pressure data from 14 discs indicated a consistent precompression pressure average of 68.16 N. Following compression, pressures increased to 125.99 N and 140.84 N for normal and parallel compression postunilateral facetectomy, respectively, and to 154.58 N and 150.46 N for bilateral models. A strong linear correlation (correlation coefficient: 0.967, P < 0.0001) between precompression and postcompression pressures emphasized the necessity of sufficient precompression pressure for achieving desired postcompression outcomes. None of the data showed a decrease in compression force to the cage with the compression maneuver. CONCLUSIONS: Both normal and parallel compression maneuvers effectively increased the pressure on the cage, irrespective of the facet joint resection status. Compression manipulation consistently enhanced compressive force on the cage. However, when baseline pressure is low, the manipulation might not yield significant increases in compression force. This underlines the essential role of meticulous precompression preparation in enhancing surgical outcomes.

Postoperative function of patients with rheumatoid arthritis after total knee arthroplasty in the last decade was comparable in the unadjusted cohort but inferior in the propensity score matched cohort with that of patients with osteoarthritis.

BACKGROUND: The perioperative pain and function of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) approach those in patients with osteoarthritis (OA). This study aimed to evaluate whether the clinical outcomes, especially functions, of patients with RA reached those of OA, utilizing a background-matched cohort. METHODS: Patients who underwent TKA between 2013 and 2021 were enrolled. Preoperative and minimum 2-year postoperative scores, specifically the Original Knee Society Score (OKSS) and New Knee Society Score (2011KSS), between RA and OA were compared. Clinical assessments were performed on unadjusted and propensity-score matched cohorts, ensuring age, sex, body mass index, and valgus deformity rate parity. RESULTS: In an unadjusted cohort involving 98 patients with RA and 560 patients with OA, patients with RA demonstrated inferior preoperative OKSS-Function Score (FS) but similar postoperative functional scores to OA patients. In the matched cohort of 83, patients with RA displayed lower preoperative OKSS- FS (median difference: 20, P < 0.001) and 2011KSS functional activities (difference: 9, P = 0.01) beyond minimum clinically important differences than patients with OA. Patients with RA improved more in OKSS-FS, yielding no postoperative difference compared with patients with OA. However, postoperative 2011KSS functional activities remained lower in patients with RA (difference: 9.5, P = 0.03), especially in advanced functions, than in those with OA. CONCLUSION: Postoperative function showed no difference between patients with RA and OA in the unadjusted cohort; within the background-matched cohort, postoperative function, especially advanced function, was inferior in patients with RA to those with OA.

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

S2 Alar Screw Insertion Accuracy and Factors Associated With Screw Loosening and Lumbosacral Nonunion.

OBJECTIVE: To investigate S2 alar screw (S2AS) accuracy and factors associated with S2AS loosening and lumbosacral nonunion. METHODS: We retrospectively reviewed patients who underwent lumbosacral fusion surgery with S2AS addition under fluoroscopy. S2AS loosening and lumbosacral nonunion were analyzed using a 1-year postoperative computed tomography. S2AS insertion accuracy was originally classified as accurate, short, anterior perforation, lateral perforation, and sacroiliac joint (SIJ) deviation among lateral perforation. Clinical data including sex, age, body mass index, fused segments, fusion procedure, primary or revision surgery, Japanese Orthopedic Association scores and complications were collected. Factors associated with S2AS loosening and lumbosacral nonunion were analyzed. RESULTS: A total of 37 patients (74 screws, age: 63.78 ± 13.57 years, female/male: 14/23 patients, body mass index: 23.11 ± 2.53, fused segments: 1-4 levels, revision: 38%) were included. S2AS loosening and lumbosacral nonunion were observed in 18 screws (13%) and 8 patients (22%) respectively. Only 35 screws (47%) were inserted accurately in our classification. Short, lateral perforation, and anterior perforation were observed in 14 screws (19%), 22 screws (30%), and 3 screws (4.1%). SIJ deviation was seen in 15 screws (20%) Factors associated with S2AS loosening were older age (P = 0.038), fusion levels (P = 0.011), and SIJ deviation (P < 0.001). S2AS loosening affects S1 pedicle screw (S1PS) loosening (P = 0.001). Furthermore, S2AS loosening is a risk factor for lumbosacral nonunion (P = 0.046). CONCLUSIONS: S2AS insertion under fluoroscopy is inaccurate. S2AS loosening induces S1PS loosening and lumbosacral nonunion. Surgeons should avoid deviating to SIJ, especially in older patients and relatively longer fusion.

Monocyte-derived transcriptomes explain the ineffectiveness of abatacept in rheumatoid arthritis.

BACKGROUND: The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA. METHODS: Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results. RESULTS: Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway. CONCLUSIONS: Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.

Management and treatment outcomes of rheumatoid arthritis in the era of biologic and targeted synthetic therapies: evaluation of 10-year data from the KURAMA cohort.

BACKGROUND: Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. METHODS: Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. RESULTS: We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. CONCLUSIONS: With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.