Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.

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.

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.

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.

Are Dental Procedures Associated With Pyogenic Vertebral Osteomyelitis?

BACKGROUND: Dental procedures can lead to bacteremia and have been considered a potential risk factor for pyogenic vertebral osteomyelitis (PVO). However, data on the association between dental procedures and PVO are limited. QUESTIONS/PURPOSES: (1) After controlling for relevant confounding variables, are dental procedures associated with an increased risk of PVO? (2) Does antibiotic prophylaxis before dental procedures effectively decrease the risk of PVO? METHODS: A case-crossover study was conducted to investigate the association between dental procedures and PVO using a Japanese claims database. The advantage of this study design is that confounding factors that do not vary over time are automatically adjusted for, because cases act as their own controls. From April 2014 to September 2021, the database included 8414 patients who were hospitalized for PVO. Of these, 50% (4182 of 8414) were excluded because they had not undergone any dental procedures before the index date, a further 0.1% (10 of 8414) were excluded because they were younger than 18 years at the index date, and a further 7% (623 of 8414) were excluded because they did not have at least 20 weeks of continuous enrollment before the index date, leaving 43% (3599 of 8414) eligible for analysis here. The mean age was 77 ± 11 years, and 55% (1985 of 3599) were men. Sixty-five percent (2356 of 3599) of patients had a diagnosis of diabetes mellitus, and 42% (1519 of 3599) of patients had a diagnosis of osteoporosis. We compared the frequency of dental procedures between a 4-week hazard period before the admission date for PVO and two control periods, 9 to 12 weeks and 17 to 20 weeks before the admission date for PVO, within individuals. We calculated odds ratios and 95% confidence intervals using conditional logistic regression analysis. RESULTS: Comparing the hazard and matched control periods within individuals demonstrated that dental procedures were not associated with an increased risk of PVO (OR 0.81 [95% CI 0.72 to 0.92]; p < 0.001). Additional analysis stratified by antibiotic prophylaxis use showed that antibiotic prophylaxis was not associated with a lower OR of developing PVO after dental procedures (with antibiotic prophylaxis: OR 1.11 [95% CI 0.93 to 1.32]; p < 0.26, without antibiotic prophylaxis: OR 0.72 [95% CI 0.63 to 0.83]; p < 0.001). Our sensitivity analyses, in which the exposure assessment interval was extended from 4 to 8 or 12 weeks and exposure was stratified by whether the dental procedure was invasive, demonstrated results that were consistent with our main analysis. CONCLUSION: Dental procedures were not associated with an increased risk of subsequent PVO in this case-crossover study. The effectiveness of antibiotic prophylaxis was not demonstrated in the additional analysis that categorized exposure according to the use of antibiotic prophylaxis. Our results suggest that the association between dental procedures and PVO may have been overestimated. Maintaining good oral hygiene may be important in preventing the development of PVO. The indications for antibiotic prophylaxis before dental procedures should be reconsidered in view of the potential risk of adverse drug reactions to antibiotic prophylaxis and the emergence of drug-resistant pathogens. Larger randomized controlled trials are needed to confirm these findings and assess the role of antibiotic prophylaxis. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

OBJECTIVE: This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimizing selection bias and adjusting the confounding patient characteristics. METHOD: The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient's background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed. RESULTS: The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P < 0.001; BARI: OR 1.07, P < 0.001), baseline CRP (TOFA: OR 1.32, P = 0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01-1.38, P = 0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P = 0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. CONCLUSION: The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis.

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.

Feasibility of total and partial uncinectomy during anterior cervical approach: MRI-based analysis of 176 patients regarding vertebral artery location.

PURPOSE: To determine the technical feasibility of uncinate process (UP) resection (uncinectomy) during anterior cervical approach with risk-avoidance of vertebral artery (VA) injury. METHODS: One hundred and seventy-six magnetic resonance imaging images with cervical spondylosis were evaluated. The diameter between UP and VA (UP-VA distance), the presence of a fat plane, and the VA's anterior-posterior position relative to UP (anterior[A], middle[M], posterior[P]) at C3-4 to C6-7 segments were investigated. Subsequently, easy-to-use classifications were developed according to the feasibility of total and partial uncinectomy. Total uncinectomy: easy (distance: > 2 mm); moderate (distance: ≤ 2 and fat plane: +); advanced (no fat plane). Partial uncinectomy: easy (distance: > 2 mm and P, A, or M position); moderate (distance: ≤ 2; fat plane: + and P position), and advanced (no fat plane and P position). RESULTS: UP-VA distance of C5-6 on the right side (left/right: 0.41/0.31 mm) was the smallest. The ratio of no fat plane of C5-6 (46.6%/49.4%) was the highest. C5-6 had a high rate of P position (7.4%/8.5%) while C6-7 had a high rate of A position (19.3%/18.2%). More than 90% individuals were classified as easy for partial uncinectomy at any vertebral segment (C3-7), while more than 30% were classified as advanced at C4-7 with the highest rate at C5-6 for total uncinectomy. CONCLUSION: When performing uncinectomy during the anterior cervical approach, the C5-6 segment may be at the greatest risk of VA injury. Hence, preoperative MR images should be thoroughly evaluated to avoid VA injury.

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.

CT-based analysis of sagittal and coronal lumbar endplate morphology: multivariate analysis of factors associated with endplate depth.

PURPOSE: Lumbar endplate morphology varies in individuals; thus, custom-made implants are sometimes more useful than standardized implants. This study aimed to analyze endplate morphology and factors associated with endplate depth using computed tomography (CT) in a non-symptomatic population. METHODS: In total, 118 lumbar CT images of non-symptomatic individuals without severe degenerative change (aged 20-79 years) were retrospectively reviewed. The following radiographic parameters were measured in each lumbar vertebral segment (T12-S1) to determine endplate depth: superior/inferior endplate depth in the midsagittal and midcoronal planes, disk angle, and height. The relationship between baseline demographics (age, sex, body mass index [BMI], Hounsfield unit of the L1 vertebral body, and pelvic incidence [PI]) and endplate depth was analyzed. RESULTS: Toward the caudal level, the superior endplate depth increased, sagittal inferior depth decreased, and coronal inferior depth increased. Multivariate analysis revealed that endplate depth was significantly associated with age (p < 0.001), while inferior endplate depth was associated with PI (p = 0.01). Superior endplate depth was associated with female sex (sagittal: p = 0.005, coronal: p = 0.002). Endplate depth, except for the inferior coronal region, was associated with low BMI (sagittal superior: p = 0.005; coronal superior and sagittal inferior: p = 0.02). CONCLUSION: Endplate depths tend to be larger toward the caudal level, particularly in the superior endplate. Surgeons should thoroughly evaluate the preoperative CT image because various endplate morphologies require attention to cage shape when performing lumbar interbody fusion, especially in patients who are older, are female, have low BMI, and have large PI. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Recurrence rate after posterior percutaneous screw fixation without anterior debridement for pyogenic spondylitis compared with conservative treatment: a propensity score-matched analysis.

PURPOSE: Previous studies have shown that percutaneous pedicle screw (PPS) posterior fixation without anterior debridement for pyogenic spondylitis can improve patient quality of life compared with conservative treatment. However, data on the risk of recurrence after PPS posterior fixation compared with conservative treatment is lacking. The aim of this study was to compare the recurrence rate of pyogenic spondylitis after PPS posterior fixation without anterior debridement and conservative treatment. METHODS: The study was conducted under a retrospective cohort design in patients hospitalized for pyogenic spondylitis between January 2016 and December 2020 at 10 affiliated institutions. We used propensity score matching to adjust for confounding factors, including patient demographics, radiographic findings, and isolated microorganisms. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence of pyogenic spondylitis during the follow-up period in the matched cohort. RESULTS: 148 patients (41 in the PPS group and 107 in the conservative group) were included. After propensity score matching, 37 patients were retained in each group. PPS posterior fixation without anterior debridement was not associated with an increased risk of recurrence compared with conservative treatment with orthosis (HR, 0.80; 95% CI, 0.18-3.59; P = 0.77). CONCLUSIONS: In this multi-center retrospective cohort study of adults hospitalized for pyogenic spondylitis, we found no association in the incidence of recurrence between PPS posterior fixation without anterior debridement and conservative treatment.

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.

Reoperation Rates of Microendoscopic Discectomy Compared With Conventional Open Lumbar Discectomy: A Large-database Study.

BACKGROUND: Microendoscopic discectomy for lumbar disc herniation has been shown to be as effective as traditional microdiscectomy or open discectomy in terms of clinical outcomes such as pain relief, and it is less invasive. Nevertheless, the reoperation rate for microendoscopic discectomy compared with microdiscectomy or open discectomy remains unclear, possibly due to difficulties in conducting follow-up of sufficient duration and in obtaining information about reoperation in other facilities. QUESTIONS/PURPOSES: (1) What is the rate of reoperation after microendoscopic discectomy for primary lumbar disc herniation on a large scale at a median of 4 years postoperatively? (2) Is there any difference in revision rate at a median of 4 years and within 90 days postoperatively based on surgical method? METHODS: We conducted a retrospective, comparative study of adult patients who underwent microendoscopic discectomy or microdiscectomy or open discectomy for lumbar disc herniation from April 2008 to October 2017 and who were followed until October 2020 using a commercially available administrative claims database from JMDC Inc. This claims-based database provided information on individual patients collected across multiple hospitals, which improved the accuracy of postoperative reoperation rates. We included 3961 patients who received microendoscopic discectomy or microdiscectomy or open discectomy between April 2008 and October 2017 in the JMDC claims database. After applying exclusion criteria, 50% (1968 of 3961) of patients were eligible for this study. Propensity score-weighted analyses were conducted in 646 patients in the microendoscopic discectomy group and in 1322 in the microdiscectomy or open discectomy group, with a median (IQR) of 4 years (3 to 6) of follow-up in both groups. Mean patient age was 42 ± 12 years in the microendoscopic discectomy group and 43 ± 12 years in the microdiscectomy or open discectomy group. Males accounted for 78% (505 of 646) of patients in the microendoscopic discectomy group and 79% (1050 of 1322) of patients in microdiscectomy or open discectomy group. The proportion of patients with diabetes mellitus in the microendoscopic discectomy group (10% [64 of 646]) was less than in the microdiscectomy or open discectomy group (15% [195 of 1322]). The primary outcome was Kaplan-Meier survivorship free from any type of additional lumbar spine surgery at a median of 4 years after the index surgery. The secondary outcome was survival probability using the Kaplan-Meier method with endpoints of any type of reoperation within 90 days after the index surgery. To determine which procedure had the higher revision rate, we conducted propensity score overlap weighting analysis, which controlled for potential confounding variables such as age, sex, comorbidities, and type of hospital as well as Cox proportional hazard models to estimate HRs and 95% confidence intervals (CIs). RESULTS: The 5-year cumulative reoperation rate was 12% (95% CI 9% to 15%) in the microendoscopic discectomy group and 7% (95% CI 6% to 9%) in the microdiscectomy or open discectomy group. After controlling for potentially confounding variables like age, sex, and diabetes mellitus, the microendoscopic discectomy group had a higher reoperation risk than the microdiscectomy or open discectomy group (weighted HR 1.57 [95% CI 1.14 to 2.16]; p = 0.004). Within 90 days of the index surgery, after controlling for potentially confounding variables like age, sex, and diabetes mellitus, we found no difference between the microendoscopic discectomy group and microdiscectomy or open discectomy group in terms of risk of reoperation (weighted HR 1.38 [95% CI 0.68 to 2.79]; p = 0.38). CONCLUSION: Given the higher reoperation risk with microendoscopic discectomy compared with microdiscectomy or open discectomy at a median of 4 years of follow-up, surgeons should select microdiscectomy or open discectomy, despite the current popularity of microendoscopic discectomy. The revision risk of microendoscopic discectomy compared with microdiscectomy or open discectomy in the long term remains unclear. Future large, prospective, multicenter cohort studies with long-term follow-up are needed to confirm the association between microendoscopic discectomy and risk of reoperation. LEVEL OF EVIDENCE: Level Ⅲ, therapeutic study.

Efficacy of personalized exercise program on physical function in elderly patients with rheumatoid arthritis at high risk for sarcopenia: study protocol for a randomized controlled trial.

BACKGROUND: Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia. METHODS: This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population. DISCUSSION: This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs. TRIAL REGISTRATION: The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm ) on January 4, 2022.

Predictors of the need for rib resection in minimally invasive retroperitoneal approach for oblique lateral interbody fusion at upper lumbar spine (L1-2 and L2-3).

BACKGROUND: This study aimed to identify factors that can predict the need for rib resection in a minimally invasive, oblique retroperitoneal approach for upper lumbar interbody fusion (OLIF at L1-3) using modern tubular retractors. METHODS: Eighty-six patients, who underwent L1-2 and/or L2-3 OLIF at a single institution, were included. Decision for rib resection was made through intraoperative fluoroscopic view (true lateral view of the desired level). Patients were divided into two groups according to rib resection (rib resection and non-rib resection groups). Baseline demographics, surgical and radiographic data, including coronal/sagittal spinopelvic parameters and perioperative complications, were compared between the groups. Logistic regression analysis was performed to identify the factors predicting the need for rib resection. RESULTS: The study cohort comprised 31 patients in the rib resection group and 55 patients in the non-rib resection group. There was no significant inter-group difference in terms of the baseline demographics. A total of 79% patients undergoing the two-level (both L1-2 and L2-3) procedures were rib-resected, while 81.6% of the patients undergoing the L2-3 level alone were not rib-resected. Endplate injuries occurred more commonly in the non-rib resection group (3% vs. 14%). Pleural laceration was observed in 6% of the patients in the rib resection group. The mean T10-L2 kyphosis was larger in the rib resection group than in the non-rib resection group (14.9° vs. 6.6°, P = 0.031). Multivariate logistic regression analysis identified the following independent predictors of the need for rib resection: an L1-2 inclusive procedure; T10-L2 kyphosis > 15.9°; and the apex of the coronal curve located above L2. CONCLUSION: The need for rib resection should be expected when performing L1-2 inclusive procedure. Even in the L2-3 alone case, aggressive decision-making for intraoperative rib resection might be required for an appropriate tubular retractor position, especially for patients with thoracolumbar kyphosis and apex vertebra of the major coronal curve located above L2.

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.

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.