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.

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.

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.

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.

IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Wrong-level spine surgery: A multicenter retrospective study.

BACKGROUND: Wrong-level spine surgery is a rare but serious complication of spinal surgery that increases patient harm and legal risks. Although such surgeries have been reported by many spine surgeons, they have not been adequately investigated. Therefore, this study aimed to examine the causes and preventive measures for wrong-level spine surgeries. METHODS: This study analyzed cases of wrong-level spine surgeries from 10 medical centers. Factors such as age, sex, body mass index, preoperative diagnosis, surgical details, surgeon's experience, anatomical variations, responses, and causes of the wrong-level spine surgeries were studied. The methods used by the surgeons to confirm the surgical level were also surveyed using a questionnaire for each surgical procedure and site. RESULTS: Eighteen cases (13 men and 5 women; mean age, 61.2 years; mean body mass index, 24.5 kg/m2) of wrong-level spine surgeries were evaluated in the study. Two cases involved emergency surgeries, three involved newly introduced procedures, and five showed anatomical variations. Wrong-level spine surgeries occurred more frequently in patients who underwent posterior thoracic surgery than in those who underwent other techniques (p < 0.01). Twenty-two spinal surgeons described the methods used to confirm the levels preoperatively and intraoperatively. In posterior thoracic laminectomies, half of the surgeons used preoperative markers to confirm the surgical level and did not perform intraoperative fluoroscopy. In posterior thoracic fusion, all surgeons confirmed the level using fluoroscopy preoperatively and intraoperatively. CONCLUSIONS: Wrong-level spine surgeries occurred more frequently in posterior thoracic surgeries. The thoracic spine lacks the anatomical characteristics observed in the cervical and lumbar spine. The large drop in the spinous process can make it challenging for surgeons to determine the positional relationship between the spinous process and the vertebral body. Moreover, unfamiliarity with the technique and anatomical variations were also risk factors for wrong-level spine surgeries.

Preoperative and Postoperative Factors Affecting Patient Satisfaction with Double-Door Laminoplasty for Cervical Spondylotic Myelopathy.

Introduction: Few articles have investigated patient satisfaction with laminoplasty in patients with cervical spondylotic myelopathy (CSM) alone, excluding other diseases, such as ossification of the posterior longitudinal ligament. In this study, we aimed to investigate patient satisfaction after double-door laminoplasty for CSM and determine the preoperative and postoperative factors that affect patient satisfaction. Methods: We retrospectively reviewed cases of laminoplasty for CSM. We measured sagittal imaging parameters (cervical lordosis [CL], C2-C7 cervical sagittal vertical axis [cSVA], and T1 slope [T1S]), Japanese Orthopaedic Association (JOA) score, and patient-reported outcomes (PROs) such as the neck disability index (NDI) and visual analog scale (VAS) preoperatively, 3 months postoperatively, and 1 year postoperatively. In addition, a multiple regression analysis was performed to investigate factors affecting patient satisfaction. Results: Ninety patients were included in the analysis. After surgery, CL decreased significantly (p<0.01), whereas cSVA increased significantly (p<0.01). No significant differences were observed in the preoperative and postoperative T1S values (p=0.61). The JOA, NDI, and VAS scores significantly improved postoperatively (p<0.01). The median patient satisfaction was 85 (range, 12-100) at 1 year postoperatively and 80 (range, 25-100) at 3 months postoperatively. In the multiple regression analysis, lower-extremity sensory disorder in the JOA score at 1 year postoperatively (p<0.01) and VAS scores for neck pain preoperatively and 1 year postoperatively (p=0.01 and p<0.01, respectively) were determined as factors affecting patient satisfaction. Conclusions: Cervical laminoplasty is a useful and satisfactory surgical procedure to restore patient function. However, patients with severe preoperative and postoperative neck pain and those with severe postoperative sensory disorders of the lower extremities may be less satisfied with the procedure. It is important to keep these things in mind when treating patients.

Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response. A single-center, retrospective study was conducted using the Kyoto University Rheumatoid Arthritis Management Alliance cohort database between 2011 and 2020. Serum IFX levels were measured using liquid chromatography-tandem mass spectrometry. An electrochemiluminescence assay was used to quantify serum levels of tumor necrosis factor-α and interleukin-6 and detect anti-drug antibodies. Eighty-four out of 310 patients were eligible for this study. The cutoff levels of biomarkers were determined by receiver operating characteristic analysis. IFX persistence was similar between groups stratified using IFX levels, tumor necrosis factor-α levels, interleukin-6 levels, and anti-drug antibodies positivity. The group with lower IFX and higher interleukin-6 levels had the worst therapy persistence (p = 0.017) and the most frequent disease worsening (90.0%, p < 0.001). Evaluating both interleukin-6 and IFX levels, not just IFX alone, enabled us to identify patients at risk of discontinuing IFX treatment. These findings support the utility of measuring IFX and interleukin-6 levels for successful maintenance therapy for RA.

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

OBJECTIVES: This multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in a real-world cohort of patients with rheumatoid arthritis. METHODS: The study included 6666 treatment courses (bDMARD-naïve or JAKi-naïve cases, 55.4%; tumour necrosis factor inhibitors (TNFi) = 3577; anti-interleukin-6 receptor antibodies (aIL-6R) = 1497; cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) = 1139; JAKi=453 cases). The reasons for discontinuation were divided into four categories (ineffectiveness, toxic adverse events, non-toxic reasons and remission); multivariate Cox proportional hazards modelling by potential confounders was used to analyse the HRs of treatment discontinuation. RESULTS: TNFi (HR=1.93, 95% CI: 1.69 to 2.19), CTLA4-Ig (HR=1.42, 95% CI: 1.20 to 1.67) and JAKi (HR=1.29, 95% CI: 1.03 to 1.63) showed a higher discontinuation rate due to ineffectiveness than aIL-6R. TNFi (HR=1.28, 95% CI: 1.05 to 1.56) and aIL-6R (HR=1.27, 95% CI: 1.03 to 1.57) showed a higher discontinuation rate due to toxic adverse events than CTLA4-Ig. Concomitant use of oral glucocorticoids (GCs) at baseline was associated with higher discontinuation rate due to ineffectiveness in TNFi (HR=1.24, 95% CI: 1.09 to 1.41), as well as toxic adverse events in JAKi (HR=2.30, 95% CI: 1.23 to 4.28) and TNFi (HR=1.29, 95%CI: 1.07 to 1.55). CONCLUSIONS: TNFi (HR=1.52, 95% CI: 1.37 to 1.68) and CTLA4-Ig (HR=1.14, 95% CI: 1.00 to 1.30) showed a higher overall drug discontinuation rate, excluding non-toxicity and remission, than aIL-6R.

Minimally invasive LLIF surgery to decrease the occurrence of adjacent-segment disease compared to conventional open TLIF.

PURPOSE: Lateral lumbar interbody fusion with percutaneous pedicle screw fixation (Mis-LLIF) can establish indirect decompression by lifting the vertebra with a large intervertebral cage, which causes less damage to the posterior elements. Thus, Mis-LLIF is expected to reduce the incidence of adjacent segment disease (ASD). The aim of the study was to compare the occurrence of ASD between Mis-LLIF and conventional open transforaminal interbody fusion (TLIF). METHODS: A total of 156 patients (TLIF group = 88, Mis-LLIF group = 68) who underwent single-level lumbar interbody fusion (L2/3, L3/4, or L4/5) at a single institution between 2003 and 2018 with minimum 2-year follow-up were retrospectively reviewed. The incidence of symptomatic ASD requiring reoperation (S-ASD) and radiological adjacent segment degeneration (R-ASD) 2 years postoperatively were investigated between 51 paired patients from both groups who were propensity score (PS) matched by demographic and baseline clinical data. The effect of characteristics arising from differences in surgical methods between Mis-LLIF and TLIF, such as the amount of distraction of the index fused level (∆H), on S-ASD and R-ASD was also examined. RESULTS: There were no significant differences in the incidence of S-ASD between the Mis-LLIF and TLIF groups (adjusted OR 1.3; 95% CI 0.41-3.9). There was no significant difference in the incidence of R-ASD between the Mis-LLIF and TLIF groups both at the cranial (adjusted OR 1.0; 95% CI 0.22-4.5) and caudal level (adjusted OR 1.5; 95% CI 0.44-5.3). On the other hand, ∆H was significantly higher in the Mis-LLIF group than in the TLIF group (3.6 mm vs. 1.7 mm, respectively, P < 0.0001), and was extracted as a significant independent risk factor for S-ASD (adjusted HR 2.7; 95% CI 1.1-6.3) and R-ASD at the cranial side (adjusted HR 6.4; 95% CI 1.7-24) in multivariable analysis with PS adjustment. CONCLUSIONS: The incidence of R-ASD or S-ASD was not significantly reduced in the Mis-LLIF group compared to the TLIF group, with greater ∆H potentially being a contributing factor. Using a thin cage in both TLIF and Mis-LLIF may decrease the occurrence of ASD.

Risk of further surgery after decompression in patients with diffuse idiopathic skeletal hyperostosis extending to the lumbar segments: focus on the number of residual lumbar/lumbosacral and sacroiliac mobile segments.

PURPOSE: Patients with diffuse idiopathic skeletal hyperostosis (DISH) that extends to the lumbar segments (L-DISH) have a high risk of further surgery after lumbar decompression. However, few studies have focused on the ankylosis status of the residual caudal segments, including the sacroiliac joint (SIJ). We hypothesized that patients with more ankylosed segments beside the operated level, including the SIJ, would be at a higher risk of further surgery. METHODS: A total of 79 patients with L-DISH who underwent decompression surgery for lumbar stenosis at a single academic institution between 2007 and 2021 were enrolled. The baseline demographics and radiological findings by CT imaging focusing on the ankylosing condition of the residual lumbar segments and SIJ were collected. Cox proportional hazard analysis was conducted to investigate the risk factors for further surgery after lumbar decompression. RESULTS: The rate of further surgery was 37.9% during an average of 48.8 months of follow-up. Cox proportional hazard analysis demonstrated that the presence of fewer than three segments of non-operated mobile caudal segments was an independent predictor for further surgery (including both the same and adjacent levels) after lumbar decompression (adjusted hazard ratio 2.53, 95%CI [1.12-5.70]). CONCLUSIONS: L-DISH patients with fewer than three mobile caudal segments besides index decompression levels are at a high risk of further surgery. Ankylosis status of the residual lumbar segments and SIJ should be thoroughly evaluated using CT during preoperative planning.

Inhibition of RANKL Expression in Osteocyte-like Differentiated Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment.

Giant cell tumors of bone (GCTBs) are locally aggressive tumors with the histological features of giant cells and stromal cells. Denosumab is a human monoclonal antibody that binds to the cytokine receptor activator of nuclear factor-kappa B ligand (RANKL). RANKL inhibition blocks tumor-induced osteoclastogenesis, and survival, and is used to treat unresectable GCTBs. Denosumab treatment induces osteogenic differentiation of GCTB cells. In this study, the expression of RANKL, special AT-rich sequence-binding protein 2 (SATB2, a marker of osteoblast differentiation), and sclerostin/SOST (a marker of mature osteocytes) was analyzed before and after treatment with denosumab in six cases of GCTB. Denosumab therapy was administered a mean of five times over a mean 93.5-day period. Before denosumab treatment, RANKL expression was observed in one of six cases. After denosumab therapy, spindle-like cells devoid of giant cell aggregation were RANKL-positive in four of six cases. Bone matrix-embedded osteocyte markers were observed, although RANKL was not expressed. Osteocyte-like cells were confirmed to have mutations, as identified using mutation-specific antibodies. Our study results suggest that treatment of GCTBs with denosumab results in osteoblast-osteocyte differentiation. Denosumab played a role in the suppression of tumor activity via inhibition of the RANK-RANKL pathway, which triggers osteoclast precursors to differentiate into osteoclasts.

Low hounsfield unit values at sagittal section on computed tomography predicts vertebral fracture following short spinal fusion.

BACKGROUND: Preoperative identification of osteoporosis during spine surgery is of critical importance. Additionally, the Hounsfield units (HU) measured using computed tomography (CT) have gained considerable attention. This study aimed to propose a more accurate and convenient screening method for predicting vertebral fractures after spinal fusion in elderly patients by analyzing the HU value of different range of interests of thoracolumbar spine. METHODS: Our sample pool for analysis consisted of 137 elderly female patients aged >70 years who underwent one- or two-level spinal fusion surgery with a diagnosis of adult degenerative lumbar disease. The HU values of the anterior 1/3 of the vertebral bodies based on sagittal plane and those of vertebral bodies based on axial plane at T11-L5 were measured using the perioperative CT. The incidence of postoperative vertebral fractures with respect to the HU value was investigated. RESULTS: Vertebral fractures were identified in 16 patients during the mean follow-up period of 3.8 years. While no significant association was found between HU value of L1 vertebral body or minimum HU value from axial plane and the incidence of the postoperative vertebral fracture, the minimum vertebral HU value of the anterior 1/3 of vertebral body from sagittal plane was associated with the incidence of the postoperative vertebral fracture. Patients with a minimum anterior 1/3 vertebral HU value of <80 had a higher incidence of postoperative vertebral fractures. The adjacent vertebral fractures occurred at the level of the vertebra with the lowest HU value, with a high probability. The existence of the vertebra with a minimum HU value of <80 within two levels of upper instrumented vertebrae was a risk factor for adjacent vertebral fracture. CONCLUSION: HU measurement of the anterior 1/3 of vertebral body predicts the risk of vertebral fracture after short spinal fusion surgery.

Predictors of the Need for Surgery in Cervical Ossification of the Posterior Longitudinal Ligament: A Retrospective Cohort Longitudinal Study Using a Claims-based Database.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to determine predictors associated with the needfor cervical ossification of the posterior longitudinal ligament (cOPLL) surgery amongindividuals with cOPLL. SUMMARY OF BACKGROUND DATA: cOPLL is a spinal disorder caused by ectopic ossification of the posterior longitudinal ligament. However, factors associated with a higher rate of surgery to treat the neurological symptoms of cOPLL are poorly understood. MATERIALS AND METHODS: This retrospective population-based cohort study using a commercial administrative claims database from JMDC Inc. (Tokyo, Japan) enrolled patients newly diagnosed with cOPLL from April 2005 to October 2020 and followed to April 2021. A total of 1506 cOPLL patients aged 18 years or older with no history of cervical spine surgery and with a record of metabolic profiles obtained at general health checkups were included. Cox proportional hazards regression models identified patient characteristics and comorbidities associated with cOPLL surgery. RESULTS: Of 1506 patients with cOPLL with a median of 1.8 years of follow-up after initial cOPLL diagnosis, 439 (29.2%) received cOPLL surgery. The 1-year cumulative incidence (95% CI) was 26.0% (23.7-28.2). In multivariable Cox proportional regression analysis, male (hazard ratio: 1.68; 95% CI: 1.26-2.24; P < 0.001) and obesity (body mass index: ≥25) (hazard ratio: 1.45; 95% CI: 1.10-1.89; P = 0.007) were associated with an increased risk of cOPLL surgery. CONCLUSIONS: In this large claims-based study of adults newly diagnosed with cOPLL, males and obesity were associated with a higher risk of cOPLL surgery. These findings may help clinicians to predict the future course of cOPLL in patients, although further research is needed to elucidate the biological role of these progression-associated factors.

[Eight mm Port-Site Hernia Following Robot-Assisted Abdominoperineal Resection for Rectal Cancer-A Case Report].

A 70s woman with a history of asthma and dyslipidemia underwent a robot-assisted abdominoperineal resection for rectal cancer. The ports were placed as per the method of Shizuoka Cancer Center and no intraoperative complications were observed. The colostomy was constructed in the left lower abdomen by the retroperitoneal route. The 12-mm port part was closed in 2 layers, the fascia and dermis, and the 8-mm port part was closed only in the dermis. The postoperative course was good; however, the patient vomited 10 days after surgery. Abdominal computed tomography revealed an incarcerated small intestine in the 8-mm port of the left abdomen, and it was diagnosed as port-site hernia incarceration. Emergency laparotomy hernia repair was performed on the day. A part of the 8-mm port was incised to 30-mm and the fascia dilatation to 30-mm was observed. The color tone of the incarcerated small intestine was good. Only adhesion peeling was performed, the small intestine was returned, and the fascia was closed. The postoperative course was uneventful and the patient was discharged 17 days after the second surgery. At the 1 year postoperative follow-up, recurrence of hernia or rectal cancer was not observed.

Identification of anti-citrullinated osteopontin antibodies and increased inflammatory response by enhancement of osteopontin binding to fibroblast-like synoviocytes in rheumatoid arthritis.

BACKGROUND: Anti-citrullinated protein/peptide antibodies (ACPAs) are present in patients at onset and have important pathogenic roles during the course of rheumatoid arthritis (RA). The characteristics of several molecules recognized by ACPA have been studied in RA, but the positivity rate of autoantibodies against each antigen is not high, and the pathogenic mechanism of each antibody is not fully understood. We investigated the role of anti-citrullinated osteopontin (anti-cit-OPN) antibodies in RA pathogenesis. METHODS: Enzyme-linked immunosorbent assays on RA patients' sera were used to detect autoantibodies against OPN. Fibroblast-like synoviocytes (FLS) isolated from RA patients were used to test the binding activity and inflammatory response of OPN mediated by anti-cit-OPN antibodies, and their effect was tested using an inflammatory arthritis mouse model immunized with cit-OPN. Anti-cit-OPN antibody positivity and clinical characteristics were investigated in the patients as well. RESULTS: Using sera from 224 RA patients, anti-cit-OPN antibodies were positive in approximately 44% of RA patients, while approximately 78% of patients were positive for the cyclic citrullinated peptide (CCP2) assay. IgG from patients with anti-cit-OPN antibody increased the binding activity of OPN to FLSs, which further increased matrix metalloproteinase and interleukin-6 production in TNF-stimulated FLSs. Mice immunized with cit-OPN antibodies experienced severe arthritis. Anti-cit-OPN antibodies in RA patients decreased the drug survival rate of tumor necrosis factor (TNF) inhibitors, while it did not decrease that of CTLA4-Ig. CONCLUSIONS: Anti-cit-OPN antibodies were detected in patients with RA. IgG from patients with anti-cit-OPN antibodies aggravated RA, and anti-cit-OPN antibody was a marker of reduced the survival rate of TNF inhibitors in RA patients.

Association of two-staged surgery with systemic perioperative complications in lateral lumbar interbody fusion for adult spinal deformity: a propensity score-weighted study.

PURPOSE: Adult spinal deformity (ASD) surgery carries a higher risk of perioperative systemic complications. However, evidence for the effect of planned two-staged surgery on the incidence of perioperative systemic complications is scarce. Here, we evaluated the effect of two-staged surgery on perioperative complications following ASD surgery using lateral lumbar interbody fusion (LLIF). METHODS: The study was conducted under a retrospective multi-center cohort design. Data on 293 consecutive ASD patients (107 in the two-staged group and 186 in the one-day group) receiving corrective surgery using LLIF between 2012 and 2021 were collected. Clinical outcomes included occurrence of perioperative systemic complications, reoperation, and intraoperative complications, operation time, intraoperative blood loss, transfusion, and length of hospital stay. The analysis was conducted using propensity score (PS)-stabilized inverse probability treatment weighting to adjust for confounding factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a PS-weighted cohort. RESULTS: In this cohort, 19 (18.4%) patients in the two-staged group and 43 (23.1%) patients in the one-day group experienced any systemic perioperative complication within 30 days following ASD surgery. In the PS-weighted cohort, compared with the patients undergoing one-day surgery, no association with the risk of systemic perioperative complications was seen in patients undergoing two-staged surgery (PS-weighted OR 0.78, 95% CI 0.37-1.63; p = 0.51). CONCLUSION: Our study suggested that two-staged surgery was not associated with risk for perioperative systemic complications following ASD surgery using LLIF.

Incidence of Surgical Site Infection Following Lateral Lumbar Interbody Fusion Compared With Posterior/Transforaminal Lumbar Interbody Fusion: A Propensity Score-Weighted Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The objective of this study was to compare the incidence of surgical site infection (SSI) after lateral lumbar interbody fusion (LLIF) and posterior/transforaminal lumbar interbody fusion ( P /TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have shown that LLIF can improve neurological symptoms to a comparable degree to P /TLIF. However, data on the risk of SSI after LLIF is lacking compared with P /TLIF. MATERIALS AND METHODS: The study was conducted under a retrospective cohort design in patients undergoing LLIF or P /TLIF for lumbar degenerative diseases between 2013 and 2020 using a hospital administrative database. We used propensity score overlap weighting to adjust for confounding factors including age, sex, body mass index, comorbidities, number of fusion levels, hospital size, and surgery year. We estimated weighted odds ratios (ORs) and 95% CIs for SSI within 30 days postoperatively. RESULTS: We compared the risk of SSI between 2874 patients who underwent LLIF and 24,245 patients who received P/TLIF Patients who had received LLIF were at significantly less risk of experiencing an SSI compared with those receiving P/TLIF (0.7% vs. 1.2%; weighted OR: 0.57; 95% CI: 0.36 -0.92; P=0.02). As a secondary outcome, patients who had received LLIF had less risk of transfusion (7.8% vs. 11.8%; weighted OR: 0.63; 95% CI:0.54 -0.73; P <0.001). CONCLUSIONS: In this large retrospective cohort study of adults undergoing lumbar interbody fusion, LLIF was associated with a significantly lower risk of SSI than P /TLIF. The small, but significantly, decreased risk of SSI associated with LLIF may inform decisions regarding the technical approach for lumbar interbody fusion.