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Abstract Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Abstract Object To investigate the factors associated with cause-specific discontinuation of long-term anti-tumor necrosis factor (TNF) agent use in patients with ankylosing spondylitis (AS). Methods AS patients who initiated first-line anti-TNF treatment between 2004 and 2018 and continued treatment for at least two years were enrolled in the study. Enrolled patients were observed until the last visit, discontinuation of treatment, or September 2022. Reasons for discontinuation of the first-line anti-TNF agent were categorized into the following: (1) clinical remission, (2) loss of efficacy, (3) adverse events, and (4) other reasons including loss to follow-up, cost, or reimbursement issues. A cumulative incidence function curve was used to visualize the cumulative failure rates over time for each specific reason. Univariable and multivariable cause-specific hazard models were utilized to identify factors associated with cause-specific discontinuation of the first-line anti-TNF agent. Results A total of 429 AS patients was included in the study, with 121 treated with adalimumab (ADA), 176 with etanercept (ETN), 89 with infliximab (INF), and 43 with golimumab (GLM). The median overall survival on the first-line anti-TNF agent was 10.6 (7.9–14.5) years. Among the patients, 103 (24.0%) discontinued treatment, with 36 (34.9%) due to inefficacy, 31 (30.1%) due to clinical remission, 15 (14.6%) due to adverse events, and 21 (20.4%) due to other reasons. Patients treated with ETN had a lower risk of discontinuation due to clinical remission compared to those receiving ADA (hazard ratio [HR] 0.45 [0.21–0.99], P = 0.048). Higher baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; HR 1.31 [1.04–1.65], P = 0.023) and INF use were linked to a higher risk of treatment discontinuation for inefficacy compared to ADA use (HR 4.53 [1.45–14.16], P = 0.009). Older age was related to an increased risk of discontinuation due to infection-related adverse events (HR 1.07 [1.02–1.12], P = 0.005), and current smoking was a risk factor for discontinuation due to other reasons (HR 6.22 [1.82–21.28], P = 0.004). Conclusion AS patients on their first anti-TNF treatment for at least two years demonstrated a favorable long-term treatment retention rate, with a 24.0% discontinuation rate over a 10.6-year overall survival period. The predictors for discontinuation varied by causes, underscoring the complexity of treatment response and the importance of personalized approaches to treatment management.

Objective Upadacitinib improved the signs and symptoms of non‐radiographic axial spondyloarthritis (nr‐axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT‐AXIS 2 nr‐axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr‐axSpA in SELECT‐AXIS 2. Methods Patients aged at least 18 years diagnosed with nr‐axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52‐week double‐blind period. Efficacy was assessed using non‐responder imputation incorporating multiple imputation (NRI‐MI) and as‐observed analyses for binary endpoints, and mixed‐effects model repeated measures for continuous endpoints. Results Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI‐MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI‐MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. Conclusion Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit–risk profile of upadacitinib treatment for nr‐axSpA.

Abstract Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

Abstract Objectives To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). Methods Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth’s penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. Results A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16–3.10), baseline diffusing capacity for carbon monoxide (DLCO)

Summary: The transcription repressor Bach2 plays a crucial role in shaping humoral immunity, but its cell-autonomous function remains elusive. Here, we reveal the mechanism by which Bach2 regulates effector cell maturation in peripheral B cells. In response to Toll-like receptor (TLR) agonists, Bach2 deficiency promotes the differentiation of follicular, but not marginal zone, B cells into effector cells, producing interleukin (IL)-6 and antibodies. This phenomenon is associated with changes in lipid metabolism, such as increases in CD36 expression, lipid influx, and fatty acid oxidation. Consistent with this, Bach2-deficient B cells exhibit elevated levels of mitochondrial oxidative stress, lipid peroxidation, and p38 activation. Mechanistically, Bach2 acts as a repressor of Cd36, and inhibition of CD36 or fatty acid oxidation reduces the differentiation of naive B cells into IL-6- and antibody-secreting cells. These results indicate Bach2 as a key metabolic checkpoint regulator crucial for maintaining a functionally quiescent state of follicular B cells.

The flavonoid diosmin (diosmetin 7-O-rutinoside) is used as a therapeutic agent for disorders of the blood vessels such as hemorrhoids and varicose veins. Diosmin is commercially produced using semi-synthetic methods involving the oxidation of hesperidin, the most abundant flavonoid in citrus fruits. However, this method produces byproducts that are toxic to the environment, and new sustainable methods to produce diosmin are required. Here, we used a synthetic biology approach to produce diosmin without generating toxic byproducts through reconstitution of the diosmin biosynthetic pathway in Nicotiana benthamiana. We first established that N. benthamiana leaves co-infiltrated with all seven genes in the flavonoid biosynthesis pathway produced high levels of luteolin, a precursor of diosmetin. We then compared the activity of modification enzymes such as methyltransferases, glucosyltransferases, and rhamnosyltransferases in Escherichia coli and in planta and selected genes encoding enzymes with the highest activity for producing diosmetin, diosmetin 7-O-glucoside, and diosmin, respectively. Finally, we reconstructed the entire diosmin biosynthetic pathway using three constructs containing ten genes encoding enzymes in this pathway, from phenylalanine ammonia lyase to rhamnosyltransferase. N. benthamiana leaves transiently co-expressing all these genes yielded 37.7 µg diosmin per gram fresh weight. To our knowledge, this is the first report of diosmin production in a heterologous plant system without the supply of a precursor. Successful production of diosmin in N. benthamiana opens new avenues for producing other commercially important flavonoids using similar platforms.

Abstract To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54–1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83–1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10–30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Abstract The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Purpose: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. Materials and Methods: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan–Meier method was used to assess treatment outcomes. Results: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. Conclusions PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Abstract Background Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. Methods This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. Results The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. Conclusions The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.

In this study, we investigate the discrepancy between the estimate of Q. He et al. [Phys. Rev. Res. 3, L032074 (2021)2643-156410.1103/PhysRevResearch.3.L032074], who observed a remarkable collapse of the exciton gap in Ta_{2}NiSe_{5} due to the electrostatic field between the scanning tunneling microscope (STM) tip and the sample, and that of a recent angle-resolved photoemission spectroscopy investigation [C. Chen et al., Phys. Rev. Res. 5, 043089 (2023)2643-156410.1103/PhysRevResearch.5.043089]. It is proposed that a critical factor contributing to this discrepancy is due to He et al.'s assumption of a constant work function of the STM tip. This assumption led to an underestimation of the tip-induced electric field. Using a literature value for the sample work function, a more substantial electric field strength is obtained, which resolves the apparent conflict between the doping estimates of these two techniques. Furthermore, our findings highlight the importance of the STM tip condition, which can significantly impact the tip work function and, consequently, influence the doping estimation in experiments involving tip-induced electric fields.

Abstract Spondyloarthritis (SpA) is a chronic inflammatory disease that results in bone ankylosis. The tissue renin-angiotensin system (RAS) is an emerging pathway potentially implicated in SpA-associated bone changes. The aim of the present study was to determine the mechanisms underlying this relationship. Sakaguchi (SKG) mice injected with curdlan (SKGc), animal models for SpA, were treated with RAS modulators, angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis). Disease activity was assessed using clinical scores and computed tomography scans. Mouse primary bone marrow monocytes (BMMs), osteoblast (OB) progenitor cells, peripheral blood monocytes (PBMCs), and bone-derived cells (BdCs) from patients with radiographic axial SpA (r-axSpA) were used to investigate the role of RAS in SpA pathogenesis. The expression of RAS components was significantly increased in SKGc mouse joints, and ARBs significantly reduced erosion and systemic bone loss, whereas ACEis did not. Osteoclast (OC) differentiation from primary BMMs, mediated by TRAF6, was inhibited by ARBs but promoted by ACEis; the modulators also exerted opposite effects on OB differentiation. Expression of RAS molecules was higher in PBMCs and BdCs of patients with r-axSpA than in control participants. ARBs inhibited OB differentiation in the BdCs of patients with r-axSpA, whereas ACEis did not. Neither ARBs nor ACEis affected OB differentiation in the control participants. In SpA, a condition characterized by RAS overexpression, ARBs, but not ACEis, inhibited OC and OB differentiation and bone progression. The findings should be taken into account when treating patients with SpA using RAS modulators.

Abstract Chirality, a fundamental concept from biological molecules to advanced materials, is prevalent in nature. Yet, its intricate behavior in specific topological systems remains poorly understood. Here, we investigate the emergence of hidden chiral domain wall states using a double-chain Su-Schrieffer-Heeger model with interchain coupling specifically designed to break chiral symmetry. Our phase diagram reveals single-gap and double-gap phases based on electronic structure, where transitions occur without topological phase changes. In the single-gap phase, we reproduce chiral domain wall states, akin to chiral solitons in the double-chain model, where chirality is encoded in the spectrum and topological charge pumping. In the double-gap phase, we identify hidden chiral domain wall states exhibiting opposite chirality to the domain wall states in the single-gap phase, where the opposite chirality is confirmed through spectrum inversion and charge pumping as the corresponding domain wall slowly moves. By engineering gap structures, we demonstrate control over hidden chiral domain states. Our findings open avenues to investigate novel topological systems with broken chiral symmetry and potential applications in diverse systems.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Abstract This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001–December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (β = 0.021, 95% confidence interval: 0.017–0.025, p 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

Abstract Background The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS. Methods We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments. Results Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed. Conclusions Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.

Background: Generally, a sufficient duration of relevant antibiotics based on an appropriate culture combined with proper surgical treatment guarantees a favorable clinical outcome in patients with pyogenic spine infections. However, a patient’s condition often deteriorates as concurrent infections occur in other organs, leading to mortality. Therefore, this study aimed to investigate the epidemiology of concurrent infections in patients with a pyogenic spine infection and estimate the rates and risks of early mortality. Methods: Patients with a pyogenic spine infection were identified using a national claims database that includes the entire population. The epidemiology of the six types of concurrent infections was investigated, and the corresponding early mortality rates and risks were estimated. The results were validated internally by bootstrapping and externally by defining two additional cohorts for sensitivity analysis. Results: Among 10,695 patients with a pyogenic spine infection, the prevalence of the six types of concurrent infections was 11.3 % for urinary tract infections, 9.4 % for intra-abdominal infections, 8.5 % for pneumonia, 4.6 % for septic arthritis or osteomyelitis of the extremities, 0.7 % for central nervous system infections, and 0.5 % for cardiac infections. Patients with a concurrent infection had approximately 4-fold greater mortality than those without (3.3 % vs. 0.8 %). The early mortality rates were particularly higher in patients with multiple or specific types of concurrent infections, including central nervous system infections, cardiac infections, and pneumonia. In addition, the mortality trends differed significantly according to the number and type of concurrent infections. Conclusions: These data on six types of concurrent infection among patients with pyogenic spinal infection can be used as a source of reference by clinicians.

Summary: Anterior cruciate ligament (ACL) reconstruction is often performed using a tendon graft. However, the predominant synthesis of fibrotic scar tissue (type III collagen) occurs during the healing process of the tendon graft, resulting in a significantly lower mechanical strength than that of normal ACL tissue. In this study, ACL-derived cells were reseeded to the tendon graft, and scaffold-induced compression was applied to test whether the compressive force results in superior cell survival and integration.Given nanofiber polycaprolactone (PCL) scaffold-induced compression, ACL-derived cells reseeded to a tendon graft demonstrated superior cell survival and integration and resulted in higher gene expression levels of type I collagen compared to non-compressed cell-allograft composites in vitro. Translocation of Yes-associated protein (YAP) into the nucleus was correlated with higher expression of type I collagen in the compression group. These data support the hypothesis of a potential role of mechanotransduction in the ligamentization process.

Abstract We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

Abstract Background To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. Methods Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. Results Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P

Purpose: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. Materials and Methods: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. Results: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. Conclusions: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

AimsTo test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).MethodsAcellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.ResultsIn the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs.ConclusionACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs.Cite this article: Bone Joint Res 2022;11(11):777–786.

Abstract Background One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. Methods A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. Results The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74–4.40, P

Objective The purpose of this study is to analyze various risk factors that can cause postoperative delirium (POD) in degenerative cervical myelopathy (DCM) patients, which may affect normal recovery and outcomes after surgery, and to help deal with them in advance and to take a medical approach. Methods A total of 148 patients aged 60 years or older who underwent laminoplasty or anterior cervical discectomy and fusion (ACDF) for DCM from 2008 to 2015 were included in this study. Incidence and multiple risk factors for development of POD were analyzed. Results POD occurred in 24 patients (16.2%). Among the 148 patients, 78 received laminoplasty, of whom 19 patients (24%) experienced delirium; the other 70 patients underwent ACDF, of whom 5 patients (7.1%) experienced delirium. History of Parkinson disease (odds ratio [OR], 178.242; p = 0.015), potassium level (OR, 3.764; p = 0.031), and surgical approach of laminoplasty over ACDF (OR, 8.538; p = 0.008) were found to be significant risk factors in a multivariate analysis. Age (OR, 1.056; p = 0.04) and potassium level (OR, 3.217; p = 0.04) were significant risk factors in the laminoplasty group. Conclusion The findings of this study suggest that the incidence and risk factors for POD may vary in patients with DCM. It is necessary to understand multiple factors that affect the development of POD.

Background/Aims The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Abstract Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

Abstract The two-dimensional (2D) assembly of gold nanoparticles (AuNPs) in a confined geometry is a rare phenomenon that has not been experimentally verified for complex systems. In this study, this process was investigated in detail using two types of block copolymers with hydrophobic and hydrophilic blocks and a series of AuNPs of three different sizes protected by hydrophobic ligands. In aqueous solutions, the selected block copolymers self-assembled into vesicular nanostructures with a hydrophobic domain in the wall, which functions as a confined geometrical space for hydrophobic AuNPs (i.e., it exerts a confinement effect and restricts the movement of AuNPs). Small-angle X-ray scattering studies revealed that AuNPs of different sizes assembled differently in the same confined geometry of the vesicular wall. In addition, optimal conditions for the formation of a regular NP array in the hydrophobic domain were determined. The AuNPs successfully self-assembled into a regular 2D lattice structure, forming a shell around the vesicle, when their size matched the thickness of the hydrophobic domain of the vesicular nanostructure. This study provides guidelines for the fabrication of nanoparticle arrays with controlled structures, which could enhance the functionality of materials and their physical properties.

Purpose: Robot-assisted radical cystectomy (RARC) optimizes patient recovery and has outcomes comparable with those of open surgery. This study aimed to compare the perioperative and oncologic outcomes of RARC in female and male patients. Materials and Methods: A retrospective cohort study of the Korean Robot-Assisted Radical Cystectomy Study Group database from 2007 to 2019 identified 749 patients (111 females and 638 males). Female were matched 1:1 to male by propensity score matching using a logistic regression. We compared perioperative outcomes, oncologic outcomes, and complications between the two groups. Results: The female group had comparable perioperative outcomes to the male group in terms of operation time, lymph node yield, positive surgical margin, blood transfusion rate, and hospitalization days. Complication rate and grade were not significantly different between the two groups. The most common complication was infection in female and gastrointestinal complications in male. We compared the 5-year overall, disease-specific, and recurrence-free survival of female and male: 58.2% vs. 68.0% (p=0.495), 75.7% vs. 79.3% (p=0.645), and 40.8% vs. 53.5% (p=0.913), respectively. On multivariable analysis, T stage (>T2), postoperative complications, and positive surgical margin were prognostic factors of poor outcome. Sex was not an independent predictor of the three survivals. Conclusions: The current study suggests that RARC in female has comparable perioperative and oncologic outcomes to those in male. The complication rate of RARC in female was comparable to that in male, but the type of complications differed by sex.

ObjectiveDeciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice.MethodsWe selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis.Results145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors.ConclusionAge, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

Abstract Background WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological changes of AS in an in vitro model. Methods The bone tissue from the facet joints was obtained from seven disease control and seven AS patients. Primary osteoprogenitor cells of the facet joints were isolated using an outgrowth method. Isolated osteoprogenitor cells from both control and AS tissues were analyzed by microarray, RT-qPCR, immunoblotting, and immunohistochemistry. The bone-forming activity of osteoprogenitor cells was assessed by various in vitro assays. β-galactosidase staining and senescence-associated secretory phenotype (SASP) using RT-qPCR were used to assess cell senescence. Results In microarray analysis, WNT16 expression was significantly elevated in AS osteoprogenitor cells compared to the control. We also validated that WNT16 expression was elevated in AS-osteoprogenitor cells and human AS-bone tissues. WNT16 treatment inhibited bone formation in AS-osteoprogenitor cells but not in the control. Intriguingly, AS-osteoprogenitor cells were stained markedly with β-galactosidase for cell senescence in WNT16 treatment. Furthermore, in an H2O2 stress-induced premature senescence condition, WNT16 treatment increased cell senescence in AS-osteoprogenitor cells and WNT16 treatment under the H2O2 stress condition showed an increase in p21 protein and SASP mRNA expression. The WNT16-induced SASP expression in AS-osteoprogenitor cells was reduced in WNT16 knockdown cultures. Conclusion WNT16 is highly expressed in AS and WNT16 treatment facilitated cell senescence in AS-osteoprogenitor cells during osteoblast differentiation accompanied by suppression of bone formation. The identified role of WNT16 in AS could influence bone loss in AS patients.

Abstract While their function, as immune checkpoint molecules, is well known, B7-family proteins also function as regulatory molecules in bone remodeling. B7–H3 is a receptor ligand of the B7 family that functions primarily as a negative immune checkpoint. While the regulatory function of B7–H3 in osteoblast differentiation has been established, its role in osteoclast differentiation remains unclear. Here we show that B7–H3 is highly expressed in mature osteoclasts and that B7–H3 deficiency leads to the inhibition of osteoclastogenesis in human osteoclast precursors (OCPs). High-throughput transcriptomic analyses reveal that B7–H3 inhibition upregulates IFN signaling as well as IFN-inducible genes, including IDO. Pharmacological inhibition of type-I IFN and IDO knockdown leads to reversal of B7–H3-deficiency-mediated osteoclastogenesis suppression. Although synovial-fluid macrophages from rheumatoid-arthritis patients express B7–H3, inhibition of B7–H3 does not affect their osteoclastogenesis. Thus, our findings highlight B7–H3 as a physiologic positive regulator of osteoclast differentiation and implicate type-I IFN–IDO signaling as its downstream mechanism.

Abstract Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood. Here, we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS, a receptor for M-CSF, leading to the generation of FMS intracellular domain (FICD) fragments. Increased levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory responses. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. The FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATc1 protein expression. Moreover, targeting the MNK1/2 pathway diminished arthritic bone erosion. These results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.

Purpose: Few studies have demonstrated the clinical significance of pretreatment serum albumin and globulin in prostate cancer (PCa). This study evaluated the association between the pretreatment albumin to globulin ratio (AGR) and clinicopathologic characteristics of nonmetastatic PCa in a large multicenter setting in Korea. Materials and Methods: This study involved 742 patients with nonmetastatic PCa who underwent radical prostatectomy (RP) in seven institutions between January 2011 and December 2012. The AGR was calculated as follows: albumin/(total protein−albumin). Patients were divided into low and high AGR groups by a cutoff value from a receiver operating characteristic curve analysis. Results: The best cutoff for the AGR was set at 1.53. The area under the curve of the AGR was 0.624 (95% confidence interval, 0.557–0.671; p

Backgrounds/Aims This study was performed to reveal the usefulness of the trabecular bone score (TBS) in assessing bone strength in patients with ankylosing spondylitis (AS) in comparison with dual-energy X-ray absorptiometry (DXA) methods. Methods A total of 215 AS patients (75.8% male) were enrolled from a single university hospital in Korea. Demographic and clinical information were assessed. Patients completed X-rays of the cervical and lumbar spine (L-spine), and spinal ankyloses were quantified using the modified Stoke AS Spine Score (mSASSS). Hip, anteroposterior and lateral L-spine bone mineral density (BMD) and TBS were assessed by DXA methods. Clinical characteristics and bone strength measurement results were compared between male and female AS patients. The accuracy of each bone strength evaluation method in predicting Fracture Risk Assessment Tool (FRAX) scores indicating moderate or higher fracture risk was compared by receiver operating characteristic curves in patients aged ≥ 40 years. Correlations between each bone strength measurement method and mSASSS were examined. Results Male patients showed higher mSASSS and less prevalent peripheral joint involvement compared to female patients (p < 0.05). TBS, hip BMD, and L-spine lateral BMD showed comparably high areas under the curve (AUCs) for predicting FRAX-major osteoporotic fractures (MOF) ≥ 10% (AUC ranged 0.72 to 0.76). TBS negatively correlated with mSASSS in both male and female patients (p < 0.01). Conclusions TBS could predict the risk of MOF and is not influenced by spinal osteoproliferation in AS patients, even in those with advanced spinal changes.

Background MUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD in Asian populations. We here investigate the association of rs35705950 with Korean patients with RA-ILD.Methods In this cross-sectional study, we genotyped rs35705950 in 2444 patients with RA. Among them, 683 patients with RA who have chest CT were divided into RA-ILD and RA-noILD. RA-ILD was classified as usual interstitial pneumonia (UIP) and other than UIP. The associations of rs35705950 with RA-ILD and its subtype were analysed using multivariable regression adjusted for age at RA diagnosis. Meta-analysis of a previously reported Japanese dataset and Korean dataset obtained for this study was conducted.Results The minor allele (T) frequency of rs35705950 was 0.37%, 1.43% and 2.38% in 2444 patients with RA, 105 patients with RA-ILD and 63 patients with UIP, respectively. Genotypic association of rs35705950 with RA-ILD was insignificant (OR 2.49, 95% CI 0.64 to 9.69, p=0.187), but showed significant association with UIP (OR 4.90, 95% CI 1.23 to 19.59, p=0.024) compared with RA-noILD. In meta-analysis (123 UIP and 878 RA-noILD) combining our data with previously reported Japanese data, this variant was found to be significantly associated with UIP (OR 3.51, 95% CI 1.19 to 10.37, p=0.023).Conclusion MUC5B variant rs35705950 is a rare but significant risk factor for Asian patients with RA-ILD with UIP, suggesting a sharing of the genetic background between Asian and Western populations.

ObjectiveThis study aimed to identify trajectories of radiographic progression of the spine over time and use them, along with associated clinical factors, to develop a prediction model for patients with ankylosing spondylitis (AS).MethodsData from the medical records of patients diagnosed with AS in a single center were extracted between 2001 and 2018. Modified Stoke Ankylosing Spondylitis Spinal Scores (mSASSS) were estimated from cervical and lumbar radiographs. Group-based trajectory modeling classified patients into trajectory subgroups using longitudinal mSASSS data. In multivariate analysis, significant clinical factors associated with trajectories were selected and used to develop a decision tree for prediction of radiographic progression. The most appropriate group for each patient was then predicted using decision tree analysis.ResultsWe identified three trajectory classes: class 1 had a uniformly increasing slope of mSASSS, class 2 showed sustained low mSASSS, and class 3 showed little change in the slope of mSASSS but highest mSASSS from time of diagnosis to after progression. In multivariate analysis for predictive factors, female sex, younger age at diagnosis, lack of eye involvement, presence of peripheral joint involvement, and low baseline erythrocyte sedimentation rate (log) were significantly associated with class 2. Class 3 was significantly associated with male sex, older age at diagnosis, presence of ocular involvement, and lack of peripheral joint involvement when compared with class 1. Six clinical factors from multivariate analysis were used for the decision tree for classifying patients into three trajectories of radiographic progression.ConclusionWe identified three patterns of radiographic progression over time and developed a decision tree based on clinical factors to classify patients according to their trajectories of radiographic progression. Clinically, this model holds promise for predicting prognosis in patients with AS.

BackgroundAnkylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment.ObjectiveTo investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS.Materials and methodsWe conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year.ResultsAmong 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0–0.7), ex-smoker 0.6 (0.0–1.5), and current smoker 0.6 (0.0–1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01–2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01–1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year.ConclusionCurrent smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

Surface damage detection, geometry measurement and monitoring are important for assessing the condition and risk of concrete structures. Therefore, to effectively assess the damage to a concrete structure, a 3D laser scanner accurately estimates the damage within a short timeframe and with less cost than the traditional inspection approaches. This study presents a framework for automated surface damage detection and structural health monitoring of a concrete structure using a X7 laser scanner (Trimble, Westminster, CO, USA). The methodology includes the use of 3D laser scanning technology to capture the 3D geometry of the concrete structure, followed by a detailed analysis of the data to identify any areas of damage or crack. The isodata and object-based image analysis (OBIA) techniques were applied to a 2D image generated from 3D cloud points. Overall accuracy (>89.6) and kappa statistics (>0.83) of both classification techniques exhibit good agreement between the classified and reference image. The OBIA technique was shown to be more effective in detecting minor cracks (

Background We aimed to analyze the effectiveness of albumin to globulin ratio (AGR) in predicting postoperative febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URS) and retrograde intrarenal surgery (RIRS). Methods From January 2013 to May 2018, 332 patients underwent URS and RIRS. The rate of postoperative fUTI and risk factors for postoperative fUTI were analyzed using logistic regression. Patients were divided into postoperative fUTI and non-postoperative fUTI (non-fUTI) groups. AGR with other demographic and perioperative data were compared between the two groups to predict the development of fUTI after URS. Results Of the 332 patients, postoperative fUTI occurred in 41 (12.3%). Preoperative pyuria, microscopic hematuria, diabetes mellitus, hypoalbuminemia, and hyperglobulinemia were more prevalent in the fUTI group. Patients in the fUTI group had larger stone size, lower preoperative AGR, longer operation time, and longer preoperative antibiotic coverage period. In a multivariable logistic analysis, preoperative pyuria, AGR, and stone size were independently correlated with postoperative fUTI (p

Background: Radiographs are widely used to evaluate radiographic progression with modified stoke ankylosing spondylitis spinal score (mSASSS). Objective: This pilot study aimed to develop a deep learning model for grading the corners of the cervical and lumbar vertebral bodies for computer-aided detection of mSASSS in patients with ankylosing spondylitis (AS). Methods: Digital radiographic examination of the spine was performed using Discovery XR656 (GE Healthcare) and Digital Diagnost (Philips). The disk points were detected between the bodies using a key-point detection deep learning model from the image obtained in DICOM (digital imaging and communications in medicine) format from the cervical and lumbar spinal radiographs. After cropping the vertebral regions around the disk point, the lower and upper corners of the vertebral bodies were classified as grade 3 (total bony bridges) or grades 0, 1, or 2 (non-bridges). We trained a convolutional neural network model to predict the grades in the lower and upper corners of the vertebral bodies. The performance of the model was evaluated in a validation set, which was separate from the training set. Results: Among 1280 patients with AS for whom mSASSS data were available, 5,083 cervical and 5245 lumbar lateral radiographs were reviewed. The total number of corners where mSASSS was measured in the cervical and lumbar vertebrae, including the upper and lower corners, was 119,414. Among them, the number of corners in the training and validation sets was 110,088 and 9326, respectively. The mean accuracy, sensitivity, and specificity for mSASSS scoring in one corner of the vertebral body were 0.91604, 0.80288, and 0.94244, respectively. Conclusion: A high-performance deep learning model for grading the corners of the vertebral bodies was developed for the first time. This model must be improved and further validated to develop a computer-aided tool for assessing mSASSS in the future.

Introduction Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported.Methods In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI).Results Of 187 patients randomised, 144 patients (77%) completed week 104. Among patients receiving continuous upadacitinib, 85.9% (AO) and 65.6% (NRI) achieved Assessment of SpondyloArthritis international Society 40 response (ASAS40) at week 104. Similar magnitude of ASAS40 responses were observed among patients who switched from placebo to upadacitinib (88.7% and 63.8%, respectively). The mean change from baseline to week 104 in Spondyloarthritis Research Consortium of Canada MRI spine and sacroiliac joint inflammation scores were –7.3 and –5.3, respectively, in the continuous upadacitinib group and –7.9 and –4.9 in the placebo-to-upadacitinib switch group. The mean (95% CI) change from baseline to week 104 in the modified Stoke Ankylosing Spondylitis Spine Score was 0.7 (0.3, 1.1) in the total group. Adverse event rate was 242.7/100 patient-years. No serious infections, adjudicated major adverse cardiovascular events, lymphoma, non-melanoma skin cancer, or gastrointestinal perforations were observed.Conclusions Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints. A low rate of radiographic progression was observed and no new safety findings were observed.