Background Lower limb rotation at the time of imaging may affect the measurement of joint line angles using plain radiographs, potentially compromising measurement accuracy. Accurate joint line angles are important for orthopaedic surgery planning and limb alignment. This study aimed to investigate the changes in distal femoral and proximal tibial joint line angles in response to limb rotation, and evaluate the correlation between these changes using digitally reconstructed radiographs (DRRs) generated from computed tomography (CT) images. Methods Preoperative CT data from 50 knees scheduled for TKA or unicompartmental knee arthroplasty (UKA) at our institution were analysed using a TKA planning software. The femur and tibia were aligned perpendicularly to their mechanical axes in the coronal and sagittal planes. The surgical epicondylar axis (SEA) and Akagi’s line were used as references for femoral and tibial rotation, respectively, with 0° defined as neutral rotation. Each bone was rotated from 20° external to 20° internal rotation in 5° increments using the software, and DRR images were generated at each position. Lateral Distal Femoral Angle (LDFA), Medial Proximal Tibial Angle (MPTA), and Posterior Tibial Slope (PTS) were measured at each rotational angle. The absolute values and their variations with rotation and correlations between each angle and their respective changes were analysed. Results At 0°, the mean ± SD values were 87.5 ± 2.4°, 83.9 ± 2.6°, and 8.4 ± 3.2° for LDFA, MPTA, and PTS, respectively. The mean changes across 20° external to 20° internal rotation were 0.3° (1.8°–0.6°), 1.1° (1.0°–1.5°), and 6.2° (1.9°–2.4°) for LDFA, MPTA, and PTS, respectively. MPTA was negatively correlated with ΔPTS (r = –0.7). Based on the MPTA values, the patients were categorized into: <82.5°, 82.5–84.5°, and >84.5° groups. ΔPTS was statistically significant different between the <82.5° (8.6 ± 2.3°) and 82.5–84.5° groups (6.9 ± 1.6°) and between the 82.5–84.5° and >84.5° groups (4.0 ± 1.9°) (p<0.05 and p<0.001, respectively). Conclusions Limb rotation significantly affects PTS, particularly in cases with greater medial inclination of the tibial plateau. Therefore, caution must be exercised when using plain radiographs for preoperative planning or postoperative evaluation.

Lower limb rotation at the time of imaging may affect the measurement of joint line angles using plain radiographs, potentially compromising measurement accuracy. Accurate joint line angle assessment is important for orthopaedic surgical planning and limb alignment. This study aimed to investigate changes in distal femoral and proximal tibial joint line angles in response to limb rotation and to evaluate the correlation between these changes using digitally reconstructed radiographs (DRRs) generated from computed tomography (CT) images. Preoperative CT data from 50 knees scheduled for total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) at our institution were analysed using TKA planning software. The femur and tibia were aligned perpendicular to their mechanical axes in the coronal and sagittal planes. The surgical epicondylar axis (SEA) and Akagi’s line were used as reference axes for femoral and tibial rotation, respectively, with 0° defined as neutral rotation. Each bone was rotated from 20° external rotation (ER) to 20° internal rotation (IR) in 5° increments using the software, and DRR images were generated at each position. The lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and posterior tibial slope (PTS) were measured at each rotational angle. The absolute values, their variations with rotation, and the correlations between each angle and its respective changes were analysed. At 0°, the mean ± standard deviation values were 87.5 ± 2.4°, 83.9 ± 2.6°, and 8.4 ± 3.2° for LDFA, MPTA, and PTS, respectively. The mean changes across the range of 20° ER to 20° IR were 0.3° (1.8°–0.6°), 1.1° (1.0°–1.5°), and 6.2° (1.9°–2.4°) for LDFA, MPTA, and PTS, respectively. MPTA was negatively correlated with ΔPTS (r = -0.7). Based on MPTA values, patients were categorised into three groups: <82.5°, 82.5–84.5°, and > 84.5°. ΔPTS was significantly different between the < 82.5° (8.6 ± 2.3°) and 82.5–84.5° (6.9 ± 1.6°) groups, and between the 82.5–84.5° and > 84.5° (4.0 ± 1.9°) groups (P < 0.05 and P < 0.001, respectively). Limb rotation significantly affects PTS, particularly in cases with greater medial inclination of the tibial plateau. Caution should be exercised when using plain radiographs for preoperative planning or postoperative evaluation.

Objectives: Locomotive syndrome stage 3 (LS3), which has been established recently, may imply a greater need for care than LS stage 0 (LS0), LS stage 1 (LS1), and LS stage 2 (LS2). The relationship between LS3 and long-term care in Japan is unclear. Therefore, this study aimed to examine this relationship. Methods: A total of 531 patients (314 women and 217 men; mean age, 75 years) who were not classified as requiring long-term care and underwent musculoskeletal examinations in 2012 were grouped according to their LS stage. Group L comprised patients with LS3 and Group N comprised those with LS0, LS1, and LS2. We compared these groups according to their epidemiology results and long-term care requirements from 2013 to 2018. Results: Fifty-nine patients (11.1%) were diagnosed with LS3. Group L comprised more patients (50.8%) who required long-term care than Group N (17.8%) (P < 0.001). Group L also comprised more patients with vertebral fractures and knee osteoarthritis than Group N (33.9% vs 19.5% [P = 0.011] and 78% vs 56.4% [P < 0.001], respectively). A Cox proportional hazards model and Kaplan-Meier analysis revealed a significant difference in the need for nursing care between Groups L and N (log-rank test, P < 0.001; hazard ratio, 2.236; 95% confidence interval, 1.451-3.447). Conclusions: Between 2012 and 2018, 50% of patients with LS3 required nursing care. Therefore, LS3 is a highrisk condition that necessitates interventions. Approaches to vertebral fractures and osteoarthritis of the knee could be key.

Background: In Japan, five JAK inhibitors (JAKinibs) are available for rheumatoid arthritis (RA) patients. As with biologic drugs (bDMARDs), there are no specific criteria for drug selection and they have been used in the order of approval, with or without MTX. In this context, the second-generation selective JAKinibs which was developed with the aim of achieving higher selectivity and reducing the risk of side effects, is also expected to improve efficacy. Objectives: Upadacitinib (UPA) has been reported to be a more selective inhibitor of JAK1 than other JAK isoforms, and head-to-head studies comparing efficacy between JAKinibs are difficult to conduct in clinical practice. The present study evaluated the efficacy of UPA in RA patients who had discontinued first-generation JAKinibs due to inadequate efficacy. Methods: At our institution, RA patients are assessed for disease activity at least once every three months. Patients with a positive rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody and a history of discontinuation of Tofacitinib (TOF) and/or Baricitinib (BAR) due to inadequate response, and who had started UPA by November 2022 were retrospectively studied. For each discontinued JAKi, one-year continuation rates were assessed by the Kaplan-Meier method, disease activity by the DAS28-ESR and SDAI, PRO by the HAQ-DI, and changes in RF as a biomarker were investigated. In addition to the UPA dose, the dose of methotrexate (MTX) and prednisolone (PSL) concomitant was also investigated. After achieving the treatment goal, MTX was tapered or discontinued following PSL, and then UPA was allowed to be tapered. Results: Forty-three patients (5 males and 38 females) were included in the study, with age at the start of UPA 67.8 ± 11.7 years, disease duration 19.0 ± 10.3 years, DAS28-ESR 4.12 ± 0.73, SDAI 8.83 ± 5.01 and HAQ-DI 1.00 ± 0.89. The two-drug JAKinibs ineffectiveness group (two-drug group) was older (mean 71.6 years), had more active disease (DAS28-ESR mean 4.43) and used more bDMARDs (mean 5.4) than the one-drug JAKinibs ineffectiveness group. Continuation rates were 81.3% for 16 patients in the TOF ineffectiveness group, 95.5% for 22 patients in the BAR ineffectiveness group and 100% for 5 patients in the two-drug group, with no significant differences (P=0.25). Overall, DAS28-ESR fell by a mean of 1.20 (P<0.01) in the continuing cases, with 28 cases achieving 3.2 or less, SDAI fell by a mean of 3.82 (P<0.01) and HAQ-DI by a mean of 0.08 (P=0.09). RF decreased from pre-commencement in 32 patients. Reasons for discontinuation were two adverse events (pneumonia and myocardial infarction), primary invalidity and patient convenience in one case each. Overall, including three Herpes Zoster (HZ) Vaccine recipients, only one patient developed HZ. UPA doses at 1 year were less than 15 mg/day in 22 patients and less than 7.5 mg/day in 17 patients. Conclusion: UPA was effective in patients with inadequate response to first-generation JAKinibs in this single-center observational study. The retention rate was high, suggesting the possibility of tapering UPA doses, mainly in patients who achieved treatment targets. Limitations of the study include a short observation period and small sample size to assess safety, and some patients with a history of multiple drug use extended the use of JAKinibs even if their response was somewhat inadequate. Further studies are needed to understand the impact on safety and efficacy, including head-to-head trials of JAKinibs for JAKinibs naïve and refractory cases and switching to UPA for patients who discontinued due to adverse events during remission or LDA with first-generation JAKinibs. REFERENCES: [1] Bonelli M, Kerschbaumer A, Kastrati K, et al. Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story. Ann Rheum Dis 2023;0:1–22. doi:10.1136/ard-2023-223850. Acknowledgements: NIL. Disclosure of Interests: None declared.

BACKGROUND CONTEXT: Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have closely investigated the factors contributing to the quality of life (QOL) in the chronic phase after thoracolumbar OVFs using detailed radiographic evaluation.PURPOSE: This study aimed to identify factors associated with the QOL in the chronic phase after thoracolumbar OVF. DESIGN: Post hoc analysis of a prospective randomized study.PATIENT SAMPLE: Participants included 195 patients with fresh thoracolumbar OVF managed conservatively with a brace who were available for radiographic analysis 48 weeks after injury.OUTCOME MEASURES: The degree of QOL impairment at 48 weeks after thoracolumbar OVF was assessed using the Japanese three-level version of the EuroQol five-dimensional questionnaire (EQ-5D) score.METHODS: Univariate and multivariate regression analyses were used to evaluate the relation-ships between the QOL and radiographic factors. RESULTS: The univariate analysis showed that age, analgesic use, T10/L5 Cobb angle on mag-netic resonance imaging (MRI), subsequent vertebral fracture, and nonunion were significantly associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. The multiple regression analysis showed that nonunion, analgesic use, subsequent vertebral fracture, and sacral slope on MRI were independently associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. Receiver operating characteristic analysis for the deterioration of QOL showed that the cutoff value for sacral slope on MRI was 35 degrees.CONCLUSIONS: This study demonstrated that nonunion, subsequent vertebral fracture, and lower sacral slope were independently associated with poorer QOL in the chronic phase of thoraco-lumbar OVF managed conservatively with a brace. Therefore, improving or preventing these fac-tors in patients with thoracolumbar OVF in the chronic phase may improve the QOL of the affected patients.(c) 2022 Elsevier Inc. All rights reserved.

Introduction Lateral lumbar interbody fusion (LLIF) has been introduced in Japan in 2013. Despite the effectiveness of this procedure, several considerable complications have been reported. This study reported the results of a nationwide survey performed by the Japanese Society for Spine Surgery and Related Research (JSSR) on the complications associated with LLIF performed in Japan. Methods JSSR members conducted a web-based survey following LLIF between 2015 and 2020. Any complications meeting the following criteria were included: (1) major vessel, (2) urinary tract, (3) renal, (4) visceral organ, (5) lung, (6) vertebral, (7) nerve, and (8) anterior longitudinal ligament injury; (9) weakness of psoas; (10) motor and (11) sensory deficit; (12) surgical site infection; and (13) other complications. The complications were analyzed in all LLIF patients, and the differences in incidence and type of complications between the transpsoas (TP) and prepsoas (PP) approaches were compared. Results Among the 13,245 LLIF patients (TP 6,198 patients [47%] and PP 7,047 patients [53%]), 389 complications occurred in 366 (2.76%) patients. The most common complication was sensory deficit (0.5%), followed by motor deficit (0.43%) and weakness of psoas muscle (0.22%). Among the patient cohort, 100 patients (0.74%) required revision surgery during the survey period. Almost half of the complications developed in patients with spinal deformity (183 patients [47.0%]). Four patients (0.03%) died from complications. Statistically more frequent complications occurred in the TP approach than in the PP approach (TP vs. PP, 220 patients [3.55%] vs. 169 patients [2.40%]; p<0.001). Conclusions The overall complication rate was 2.76%, and 0.74% of the patients required revision surgery because of complications. Four patients died from complications. LLIF may be beneficial for degenerative lumbar conditions with acceptable complications; however, the indication for spinal deformity should be carefully determined by the experience of the surgeon and the extent of the deformity.

Commentary Since the first reports of ventral approaches to cervical disc pathology were introduced in the 1950s1,2, anterior cervical discectomy and fusion (ACDF) has become one of the most common procedures performed by spine surgeons for patients with symptomatic cervical spondylosis. A solid osseous fusion is necessary to achieve good clinical results. Spine surgeons have been trying to modify their own procedures using a variety of interbody fusion materials, such as structural autograft, allograft, titanium, polyetheretherketone (PEEK), or carbon fiber-reinforced polymer, with or without non-structural autograft or allograft. Although a number of clinical investigations have been performed evaluating how to achieve solid fusion, attention has not been focused on the time to fusion. Sheng et al. performed a prospective randomized controlled trial (RCT) and showed that cervical fusion could be achieved earlier after uncovertebral joint fusion (UJF) compared with end plate space fusion (ESF) for patients with single-level cervical spondylosis. Although no significant difference was observed in the fusion rate at 12 months, their results showed that fusion rates at 3 and 6 months after ACDF were much higher in the UJF group than in the ESF group (UJF versus ESF: 66.7% versus 13.2% at 3 months, 94.1% versus 66.7% at 6 months). Based on a previously published goat study3, the authors speculated that the reasons for these results were due to several factors. The uncovertebral joint had several anatomical advantages over ESF: a narrower gap, higher mechanical load, better osteogenic potential, and better blood supply, which could be advantageous for earlier cervical fusion. If early fusion can be achieved by UJF in ACDF, it may be possible to avoid issues with prolonged cervical bracing, such as cervical stiffness, dysphagia, and pressure ulcer, and to increase patient satisfaction and quality of life. It is also beneficial, especially for active patients (athletes), to return to play faster. Thus, the authors propose a new concept that the UJF can provide advantages over conventional ESF for the ACDF procedure. On the other hand, it is well known that the spinal fusion rate is dependent on the radiographic fusion criteria. Although Sheng et al. used relatively strict fusion criteria (both “interspinous mobility of ≤1 mm and formation of a bone bridge in the target area” confirmed by computed tomography [CT] had to be met simultaneously), a recent systematic literature review of osseous fusion after anterior cervical discectomy identified fusion rates for ESF of 51.1% at 3 months and 78.3% at 6 months, which are higher than those in the study by Sheng et al. (13.2% at 3 months and 66.7% at 6 months)4. Although the study was a prospective RCT, it was performed in a single center. It is still unclear whether the early fusion can be achieved when different spine surgeons are conducting the procedure using this new device in the same manner. Different surgical exposure, different graft materials, and/or different implant bed preparation might cause unknown differences in patient outcomes. In spite of these limitations, the results of this RCT performed by Sheng et al. provide a potential new advance for ACDF procedures. Future research regarding patient satisfaction and quality of life achieved by early fusion in the uncovertebral joints is eagerly anticipated.

Background In practice, bDMARDs and subsequent first-generation JAK inhibitors (JAKi) have significantly improved the management of rheumatoid arthritis (RA), but there are still patients refractory or intolerant to multiple b/tsDMARDs. The fact that first-generation JAKi inhibit more than one JAK molecule has given rise to hopes that second-generation JAKi with enhanced kinase selectivity may maximize efficacy and enable a safer profile. Although a matched-adjusted indirect comparative study, differences in efficacy between some of the two JAKi drugs have been demonstrated, suggesting that second-generation JAKi may be effective for RA patients who are intolerant or have inadequate responses to first-generation JAKi. Objectives We evaluated the real-world course of upadacitinib (UPA), a second-generation JAKi, in a single-center cohort of RA patients, including refractory patients with resistance to first-generation JAK inhibitors. Methods All RA patients who started UPA between May 2021 and June 2022, including those who had previously received tofacitinib (TOF) and/or baricitinib (BAR), were eligible for the study. Kaplan-Meier survival rates were calculated based on ineffectiveness or intolerance as the reason for discontinuation. DAS28-ESR score, PRO (VAS for pain and stiffness), and patient satisfaction on a 7-point scale were recorded at baseline, 3 months, and 6 months. In addition, RF factor antibody titers before and after UPA administration, concomitant MTX and PSL doses, and UPA dose at 6 months were recorded. The above items were evaluated in subgroups of JAKi-non-use cases and the number of JAKi used in the past. In addition, reasons for discontinuation of administration were also investigated. Results UPA was administered to 122 patients, 85.2% of whom were female, age (S.D.) 69.7 (11.9) years, weight 52.5 (8.4) kg, duration of RA (S.D.) 15.8 (10.3) years, and 97.5% of whom were RF or anti-CCP antibody positive. A median of 2.5 bDMARDs had been administered, including 37 patients who received IL-6 inhibitors. 52 patients (1st JAKi group) did not use any JAKi, 51 patients (2nd JAKi group) used one type (15 TOF, 36 BAR), and 19 patients (3rd JAKi group) used two types. Survival rates at 6 months were 92.3%, 90.2%, and 94.7% (P=0.83) in each group, and none of the 82 patients who could be followed for more than 12 months discontinued between 6 and 12 months. The mean DAS28-ESR (S.D.) at baseline was 3.91 (0.78) overall, but significantly improved to 2.79 (0.82) at 6 months (P<0.05). 67.3%, 70.6% and 47.4% of patients in each group had low disease activity. The VAS for pain and stiffness improved significantly in the 1st and 2nd JAKi groups, including treatment satisfaction. 88% of patients had decreased RF factor antibody titer. 62.5% of patients received UPA less than 7.5 mg/day at 6 months, including those who received UPA every other day. The rate of concomitant use of PSL (<5 mg) remained unchanged at 10.7%, and the rate of MTX decreased from 27.7% to 7.1%, mainly in the 1st JAKi group. 4 patients developed herpes zoster within 6 months and UPA was resumed after a temporary suspension. 2 patients discontinued UPA due to inadequate efficacy and 8 due to adverse events. Adverse events requiring hospitalization were bacterial pneumonia, putaminal hemorrhage, and sudden death with suspected acute myocardial infarction. Conclusion UPA was effective in RA patients, including first-generation JAKi-resistant patients, with few cases of discontinuation due to inadequate efficacy. Although some Japanese patients taper off UPA due to their light weight, advanced age, or complications, more than 60% of patients maintained efficacy with UPA at 7.5 mg/day or less, suggesting that taper-off is feasible. After disease activity decreased, tapering or discontinuation of concomitant MTX was prioritized, but there were no cases of apparent flares, again confirming the efficacy of UPA alone. In addition to the long-term safety of UPA, head-to-head between JAKi and JAKi to bDMARDs should be considered in the future. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have investigated the factors contributing to residual low back pain in the chronic phase after OVFs by using radiographic evaluation. We examined the contribution of nonunion, vertebral deformity, and thoracolumbar alignment to the severity of residual low back pain post-OVF. This post hoc analysis of a prospective randomized study included 195 patients with a 48-week follow-up period. We investigated the associations between radiographic variables with the visual analog scale (VAS) scores for low back pain at 48 weeks post-OVF using a multiple linear regression model. Univariate analysis revealed that analgesic use, the local angle on magnetic resonance imaging, anterior vertebral body compression percentage on X-ray, and nonunion showed a significant association with VAS scores for low back pain. Multiple regression analysis produced the following equation: VAS for low back pain at 48 weeks = 15.49 + 0.29 × VAS for low back pain at 0 weeks + (with analgesics: +8.84, without analgesics: −8.84) + (union: −5.72, nonunion: −5.72). Among local alignment, thoracolumbar alignment, and nonunion, nonunion independently contributed to residual low back pain at 48 weeks post-OVF. A treatment strategy that reduces the occurrence of nonunion is desirable.

Introduction and importance:Iliopsoas and iliacus abscesses are caused by hematogenous and lymphatic infections and the spread of inflammation in neighboring organs. A small number of cases have been reported in which inflammation spread not only within the iliopsoas muscle but also to the thigh. Here we report a case of retroperitoneal infiltration and perforation of cecal cancer that caused extensive abscess formation from the iliacus muscle to the thigh.Case presentation:An 80-year-old man who had undergone chemotherapy for cecal cancer had abdominal pain and right thigh pain without any particular attraction. CT images showed extensive abscess formation from the iliacus muscle to the subcutaneous part of the thigh due to retroperitoneal infiltration and perforation of cecal cancer. Ileocecal resection, colostomy, and retroperitoneal abscess drainage were performed for perforation of cecal cancer and pelvic abscess. Although the thigh was initially drained by a small incision, the infection did not heal. Extensive debridement and drainage were required for all of the contaminated areas, and after all the infection was completely cured.Clinical discussion:The optimal treatment for an abscess that has spread from the inguinal region to the thigh is unclear. In this case, active debridement and drainage of the infected area were effective and should have been done early.Conclusion:We believed that debridement and drainage should have been performed from the time of the first surgery not only by the small incision drainage but also for all of the contaminated areas when the infection had been widespread.

Abstract Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. The present trial failed to show a significant effect of G-CSF in primary end point.

Background Janus kinase inhibitors (JAKi) are effective in the treatment of patients with difficult-to-treat rheumatoid arthritis (D2T RA), regardless of previous use of biological disease-modifying antirheumatic drugs (bDMARDs), and receive equal billing with biological therapies in the latest version of the EULAR recommendations for treatment of RA 1 . However, as with bDMARDs, cases of discontinuation due to intolerance or inadequate response have been observed in patients treated with the so-called first-generation JAKi, leading to the development of a new generation of JAKi that aims to maximize efficacy and improve safety by enhancing kinase selectivity. The results of randomized controlled trials and meta-analyses suggest that the efficacy and safety of Upadacitinib (UPA) treatment are favorable. Although there have been no head-to-head trials between JAKi, a matched-adjusted indirect comparative study has shown a difference in efficacy between JAKi 2 , suggesting that the new generation of JAKi may be effective in rheumatoid arthritis patients with intolerance or inadequate response to first-generation JAKi. It is already apparent that a clear need exists for a JAK-IR trial to give guidance in those difficult patients who are JAKi non-responders 3 . Objectives To evaluate real world efficacy of a second-generation JAK1-selective JAKi UPA in single-center cohort of RA patients who had discontinued first-generation JAKi. Methods Patients with RA who had discontinued tofacitinib and/or baricitinib due to inadequate response or intolerance, regardless of whether they had used bDMARDs or not, were eligible for the study if they had received UPA by October 2021 and had been followed up for at least 12 weeks. Endpoints were Kaplan-Meier survival rate with inadequate response or intolerance as reasons for discontinuation, various disease activity assessments (DAS28-ESR, SDAI, CDAI, etc.), and patient reported outcomes (visual analogue scales (VASs) such as pain and stiffness, HAQ-DI, FACIT-Fatigue Scale, etc.) at 12 weeks. In addition, the reasons for discontinuation were investigated. Results Fifty-one patients were included in the study, all of whom had D2T RA and had used at least one bDMARD as well as JAKi. The mean (median) age was 72.7 (77) years, disease duration 18.0 (17) years, number of bDMARDs used 3.34 (3), number of JAKi used 1.3(1), 5 patients with methotrexate, 6 patients with prednisolone, and DAS28-ESR 3.83 (3.9). At 12 weeks, the overall survival rate was 94% (94.6% in 37 cases used as 2nd JAKi and 92.9% in 14 cases used as 3rd JAKi). For reference, there was no significant difference from the 100% of the 15 cases used as the 1st JAKi (P=0.49). DAS28-ESR <3.2 and <2.6 were achieved in 60.8% and 29.4%, VASs for pain and stiffness decreased by a mean of 12.9 mm (9 mm) and 12.1 mm (7 mm), respectively, and FACIT-Fatigue scale improved by a mean of 3.0 (1). The reasons for discontinuation in the three patients were inadequate efficacy in two and leg cramps due to venous thromboembolism in one. Conclusion UPA is more selective for JAK1 than first generation JAKi, and is expected to reduce adverse reactions caused by inhibition of JAK family members other than JAK1. The present study suggests that UPA is effective and well tolerated, regardless of the number and type of first-generation JAKi used in the past, albeit for a short period of time. Limitations include the small number of cases and the short time frame for discussing adverse reactions. References [1]Smolen JS, Landewé BM, Bijlsma WJ et al., EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020; 79 :685–699. [2]Christopher JE, Ruta S, Vishvas G et al. A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis. Rheumatol Ther 2021; 8:167–181. [3]Peter Nash, Clinical use of Jak 1 inhibitors for rheumatoid arthritis. Rheumatology , Volume 60, Issue Supplement_2, May 2021, Pages ii31–ii38 Disclosure of Interests None declared

Background: In clinical practice, when refractory rheumatoid arthritis (RA) is present, of which the definition implies previous use of at least two biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)), the next treatment choice often made is a bDMARD of another class (non-TNFis) [1]. However, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARDs treatment reduces their response [2]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. The choice of therapeutic agents for refractory RA is increasing, and its efficacy is expected. On the other hand, it is also true that some patients discontinued JAKis at a rate that cannot be overlooked because of insufficient efficacy. Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(3) Objectives: To evaluate real world efficacy of approved JAKis switching in patients with D2T RA who were unable to control their disease activity due to insufficient efficacy despite the sequential use of multiple bDMARDs and JAKis, focusing on the drug retention rate. Methods: In our hospital, RA was diagnosed according to the 1987 or 2010 classification criteria, and when two or more bDMARDs (including both TNFis and non-TNFis) were inadequately effective, it was defined as D2T RA. We retrospectively investigated patients who switched to JAKis for D2T RA. The drug retention rate was investigated by the Kaplan-Meier method, and the difference was tested by the Logrank test. Results: The 1-year retention rate of JAKis for D2T RA was 50.8% in TOF 38 cases [28 women, age average 70.2 years, disease duration average 12.4 years, past bDMARDs use average 3.5 drugs, MTX combination 9 cases, DAS28 ESR average 4.11] and 66.3% in BAR 35 cases [26 cases, 73.0 years old, 14.8 years, 4.17 agents, 9 cases, 3.68], and there was no significant difference (P = 0.30). Among them, there were 17 cases [11 cases, 70.6 years old, 13.5 years, 4.18 drugs, 2 cases, 3.65] of switching between JAKis, all of which were switching from TOF to BAR. The 1-year retention rate was 45.8% [reason for discontinuation: insufficient effect in 3 cases, adverse events in 6 cases], which was not significantly different but tended to be lower than 72.7% [reason for discontinuation: insufficient effect in 1 case, adverse event in 2 cases, patient’s convenience in 1 case] in 16 patients [13 cases, 76.3 years old, 17.1 years, 3.19 drugs, 7 cases, 3.69] who received BAR as the first JAKi for D2T RA patients (P = 0.089). Conclusion: Although the number of cases is small in the retrospective survey, it is suggested that the retention rate of BAR switched to D2T RA may be slightly lower in patients with a history of TOF discontinuation due to insufficient efficacy than in JAKi naive patients. It is expected that the number of new JAKi usage cases will increase in the future, and it is necessary to consider switching between other JAKis in addition to switching from BAR to TOF. References: [1]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77. [2]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25. [3]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344. Disclosure of Interests: None declared

Background: Studies on the clinical and radiographic risk factors for the residual low back pain beyond 6 months after osteoporotic vertebral fractures (OVFs) are lacking. Hence, this study aimed to characterize a patient population with residual low back pain 48 weeks after acute OVFs and to identify the risk factors associated with residual low back pain. Methods: This prospective multicenter study included 166 female patients aged 65-85 years with acute one-level OVFs. We defined the residual low back pain as visual analog scale (VAS) for low back pain >3.5 at 48 weeks in this study, as VAS score >3.5 is used to describe moderate or severe pain. Thus, outcome and risk factor analyses were performed by comparing patients with VAS scores <3.5 and > 3.5. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and 48 weeks. Results: Of the 166 patients analyzed, 58 complained of residual low back pain at 48 weeks after OVFs. At 0 weeks, the VAS score was significantly higher, and the JOABPEQ mental health score and anterior vertebral body compression percentage were significantly lower in patients with persistent pain 48 weeks after OVFs. The independent risk factors in the acute phase for persistent pain 48 weeks after OVFs were a high VAS score, MRI T2 fluid-intensity image pattern, and a lower anterior vertebral body compression percentage. Conclusions: Severe low back pain, MRI T2 fluid-intensity image pattern, and severe vertebral body collapse in the acute phase were significant risk factors for residual low back pain 48 weeks after OVFs. Patients with acute OVFs who have these risk factors should be carefully monitored for the possible development of residual chronic low back pain. (C) 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Study Design. Prospective cohort study. Objective. To characterize a patient population with nonunion after acute osteoporotic vertebral fractures (OVFs) and compare the union and nonunion groups to identify risk factors for nonunion. Summary of Background Data. While OVFs are the most common type of osteoporotic fracture, the predictive value of a clinical assessment for nonunion at 48 weeks after OVF has not been extensively studied. Methods. This prospective multicenter cohort study included female patients aged 65 to 85 years with acute one-level osteoporotic compression fractures. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and at 48 weeks to confirm the diagnosis and union status. The patient-reported outcome measures included scores on the European Quality of Life-5 Dimensions (EQ-5D), a visual analogue scale for low back pain, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) at 0, 12, and 48 weeks. Results. In total, 166 patients completed the 12-month follow-up, 29 of whom had nonunion. Patients with nonunion at 48 weeks after OVF had lower EQ-5D and JOABPEQ walking ability, social life function, mental health, and lumbar function scores than those with union at 48 weeks after injury. The independent risk factors for nonunion after OVF in the acute phase were a diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI. The anterior vertebral body compression percentage and JOABPEQ social life function scores were independent risk factors at 12 weeks. Conclusion. A diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI were independent risk factors for nonunion in the acute phase. Patients who have acute OVFs with these risk factors should be carefully monitored for nonunion. Level of Evidence: 2

INTRODUCTION:Nontuberculous mycobacterial (NTM) infections of the musculoskeletal system are uncommon. Such infections are typically acquired by direct inoculation after penetrating trauma, surgical procedures, or needle injections. There are no reported cases of NTM infection after arthrocentesis for idiopathic hemarthrosis of the knee. Here we report a case of NTM infection in the knee that developed after arthrocentesis for idiopathic hemarthrosis of the knee.PRESENTATION OF CASE:The patient was an 85-year-old woman who experienced swelling of the left knee. An arthrocentesis was carried out, and hemarthrosis was found. The patient was referred to our hospital for repeated recurrence of hematoma of the knee. Significant swelling was observed in the suprapatellar sac. Magnetic resonance imaging examination revealed a mass at the suprapatellar sac. Laboratory data showed elevation of inflammatory markers. Debridement was performed under arthroscopy and samples were collected for culture. Although routine microbiological cultures were negative, the patient continued to experience knee swelling and laboratory data showed high C-reactive protein levels. Therefore, open debridement was carried out. At 4 weeks after the first surgical treatment, intraoperative cultures yielded Mycobacterium intracellulare. At this point, we diagnosed septic arthritis of the knee due to NTM infection. The patient showed an excellent prognosis with three-drug medical treatment for 1 year.CONCLUSION:Clinically, diagnosis of septic arthritis due to NTM infection is not easy. Because selection of examination depends on clinical suspicion, NTM infections should be considered for patients with elevation of inflammatory markers after episodes of surgical procedures, and/or needle injections.

Aim The 25‐question Geriatric Locomotive Function Scale (hereafter, “GLFS‐25”) is a simple screening tool to detect elderly individuals at high risk of locomotive syndrome and promote interventions. This cohort study aimed to clarify if it can predict the need for nursing care certification in the near future. Methods Participants were 531 Japanese adults aged ≥65 years who had undergone a healthcare checkup in 2012 and never received nursing care certification until 2012. We collected baseline information and conducted a physical examination in 2012. We investigated the presence of nursing care certification and care need level from 2013 to 2018. Relationships of these factors with nursing care certification after 6 years were assessed. A receiver operating characteristic curve for both the GLFS‐25 and physical examination were used to determine optimal threshold value. Results From 2013 to 2018, 114 volunteers (21.4%) applied for nursing care certification and 29 volunteers died. The group with nursing care certification (over support level 1) had an average age of 79.9 years and a mean score of 17.8 on the scale. Those without nursing care certification had an average age of 74.1 years and a mean score of 8.7. When the GLFS‐25 score was 12.5, sensitivity was 0.658 and specificity was 0.760. The area under the curve was 0.736 (95% confidence interval 0.682–0.789). Conclusions The GLFS‐25 has enabled early detection of individuals with locomotive syndrome who are more likely to need nursing care certification in the near future. We propose using a cutoff score of 13 for the scale. Geriatr Gerontol Int 2021; 21: 492–497 .

Background: In 20-30% of rheumatoid arthritis (RA) patients, the first biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)) is ineffective, and among the patients who do respond to therapy, 20% is faced with secondary ineffectiveness within the first 2 years of treatment [1]. In practice, when refractory RA is present, of which the definition implies previous use of at least two bDMARDs (generally TNFis), the next treatment choice often made is a bDMARD of another class (non-TNFis) [2]. On the other hand, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARD treatment reduces their response [3]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. Objectives: Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(4). We evaluated real world efficacy of approved JAKis and factors that may help to continue them in patients with D2T RA. Methods: Patients who had inadequate response to two or more bDMARDs (including both TNFis and non-TNFis) at our hospital by December 2019 were defined as D2T RA, and patients who switched to JAKis were retrospectively investigated. The drug retention rate was determined by Kaplan-Meier method, and the difference was tested by Logrank test. Multiple regression analysis was used as the statistical method to predict continuation of JAKis for more than 1 year, with patient background (age, gender, during the disease, number of bDMARDs used, with or without methotrexate and/or glucocorticoids, disease activity score assessing 28 joints using erythrocyte sedimentation rate’ presence of rheumatoid factor/anti-CCP antibody, matrix metalloproteinase 3 value, Health Assessment Questionnaire disability index) at the time of initiation as an explanatory variable. Results: A total of 915 bDMARDs had been administered to 394 RA patients. The retention rate of bDMARDs and the number of bDMARDs used were 89.3% and 1.48 bDMARDs at 1 year, 67.7% and 2.27 bDMARDs at 5 years, and 52.0% and 3.15 bDMARDs at 10 years, respectively. The retention rate of JAKis at 1 year was 60.2% in 65 patients with tofacitinib (TOF) and 67.2% in 70 patients with baricitinib (BAR) (P=0.38). Among them, the drug retention rate in D2T RA patients was 50.8% in 38 TOF patients and 66.3% in 35 BAR patients with no significant difference (P=0.30). There were no patient background factors that significantly predicted continuation at 1 year for any JAKis. Conclusion: Despite the limited number of patients and the retrospective nature of the study, TOF and BAR were shown to be effective options for D2T RA, regardless of patient background such as disease activity or number of bDMARDs used. Other JAKis and switches between JAKis need to be investigated in the future. References: [1]Schaeverbeke T, Truchetet ME, Kostine M et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016;55:210_20. [2]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77. [3]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25. [4]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344. Disclosure of Interests: None declared

OBJECTIVE:Extensive corrective fusion surgery was performed on elderly patients with adult spinal deformity (ASD) to improve abnormal posture. Varying improvements in postoperative walking function were expected owing to differences in muscular strength and bone quality between patients in their 40s and those over 75 years of age. The purpose of this study was to compare preoperative and postoperative gait posture and physical functionality in elderly patients with ASD who underwent extensive corrective fusion to the thoracic spine. METHODS:A prospectively maintained surgical database was reviewed for patients with ASD who underwent corrective fusion surgery (thoracic spine to pelvis) between 2011 and 2016. The cohort was divided into three age groups: nonelderly (40-64 years), young-old (65-74 years), and old-old (> 75 years). Patients underwent a 4-m walk test preoperatively and 2 years postoperatively to measure gait-trunk tilt angle and walking speed (meters per minute). RESULTS:Among 291 patients with ASD who underwent corrective fusion surgery, 56 patients (14 men and 42 women; mean age 68.8 years) were included. Mean preoperative gait-trunk tilt angle (12.9° vs 5.2°, p < 0.01) and walking speed (41.2 m/min vs 45.7 m/min, p < 0.01) significantly improved postoperatively. Intergroup analysis revealed that the mean preoperative gait-trunk tilt angles in the nonelderly (n = 13), young-old (n = 28), and old-old (n = 15) groups were 11.9°, 10.0°, and 19.3°, respectively; postoperatively, these improved to 4.5°, 4.5°, and 7.2°, respectively. Mean preoperative walking speeds of 47.9, 40.0, and 37.7 m/min improved to 52.4, 44.8, and 41.5 m/min postoperatively in the nonelderly, young-old, and old-old groups, respectively. There were no statistically significant differences in degree of improvement in gait-trunk tilt angle and walking speed among groups. CONCLUSIONS:Extensive corrective fusion surgery improved the postoperative walking posture of patients with ASD. Statistical analysis of gait measurements demonstrated intergroup equivalence, indicating comparable improvement in physical functionality in elderly and middle-aged patients after corrective fusion surgery.

STUDY DESIGN:Retrospective longitudinal cohort study.OBJECTIVE:This study aimed to elucidate factors affecting the likelihood of achieving minimum clinically important difference (MCID) to patient-reported outcomes defined by the Scoliosis Research Society-22r (SRS-22r) among patients with adult spinal deformity (ASD) who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis.SUMMARY OF BACKGROUND DATA:Achieving MCID for SRS-22r parameters was a measure of surgical efficacy. Patient characteristics and surgical and radiographic factors that affect the likelihood of achieving MCID for SRS-22r parameters are unknown.METHODS:Data from patients with ASD who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis during 2010 to 2016 were retrospectively reviewed. Data from a total of 167 patients with ≥2 years of follow-up were included. Multivariate analysis was used to investigate factors associated with the likelihood of achieving MCID for each of the SRS-22r domains (Function, Pain, Subtotal) 2 years after surgery. The following MCID values were used: 0.90 for Function, 0.85 for Pain, and 1.05 for the Subtotal.RESULTS:MCID achievement rate was 36.5% for Function, 46.1% for Pain, and 44.3% for the Subtotal domain. In multivariate analysis, preoperative SRS-22r Function (odds ratio [OR] = 0.204, 95% confidence interval [CI] 0.105-0.396) increased the likelihood of achieving MCID for SRS-22r Function. Preoperative SRS-22r Subtotal (OR = 0.211, 95% CI, 0.107-0.413), preoperative pelvic tilt (OR = 1.072, 95% CI, 1.012-1.136), preoperative pelvic incidence minus lumbar lordosis (OR = 0.965, 95% CI, 0.934-0.997), and postoperative sagittal vertical axis (OR = 0.985, 95% CI, 0.974-0.995) affected the likelihood of achieving MCID for the SRS-22r Subtotal.CONCLUSION:Patients with poor preoperative health-related quality of life were more likely to achieve improvement in SRS-22r parameters after extensive corrective fusion surgery for ASD. Achieving postoperative sagittal alignment increased the likelihood of achieving MCID for the SRS-22r Subtotal domain.Level of Evidence: 3.