Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma.

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.

Radix Paeoniae Rubra stimulates osteoclast differentiation by activation of the NF-κB and mitogen-activated protein kinase pathways.

BACKGROUND: Radix Paeoniae Rubra (RPR), a traditional Chinese herb, has anti-inflammatory and immuno-regulatory properties. This study explored the effects of RPR on stimulation of osteoclast differentiation in RAW264.7 cells and peripheral blood mononuclear cells (PBMC)s. METHODS: The mature osteoclasts were measured by bone resorption assays and TRAP staining. JNK, ERK, p38 and NF-κB inhibitors were used applied in order to verify their contribution in RPR-induced osteoclast differentiation. The NF-κB and MAPK pathways were evaluated by western blotting, RT-PCR and luciferase assay. RESULTS: RPR induced osteoclast differentiation in a dose-dependent manner and induced the resorption activity of osteoclasts differentiation of RAW264.7 cells and PBMCs. Western blotting showed that RPR treatment induced phosphorylation of JNK, ERK, and p38 in RAW 264.7 cells. Treatment of JNK, ERK, and p38 MAP kinase inhibitors verified the contribution of JNK, ERK and p38. RPR treatment induced c-Fos and NFATc1 protein expression; NF-κB inhibitor treatment and luciferase assay verified the contribution of the NF-κB pathway. CONCLUSIONS: This study demonstrated the interesting effect, in which RPR stimulated osteoclast differentiation in murine RAW264.7 cells and human monocytes.

High glucose induces vascular endothelial growth factor production in human synovial fibroblasts through reactive oxygen species generation.

BACKGROUND: Diabetes is an independent risk factor of osteoarthritis (OA). Angiogenesis is essential for the progression of OA. Here, we investigated the intracellular signaling pathways involved in high glucose (HG)-induced vascular endothelial growth factor (VEGF) expression in human synovial fibroblast cells. METHODS: HG-mediated VEGF expression was assessed with qPCR and ELISA. The mechanisms of action of HG in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the VEGF promoter. RESULTS: Stimulation of OA synovial fibroblasts (OASF) with HG induced concentration- and time-dependent increases in VEGF expression. Treatment of OASF with HG increased reactive oxygen species (ROS) generation. Pretreatment with NADPH oxidase inhibitor (APO or DPI), ROS scavenger (NAC), PI3K inhibitor (Ly294002 or wortmannin), Akt inhibitor, or AP-1 inhibitor (curcumin or tanshinone IIA) blocked the HG-induced VEGF production. HG also increased PI3K and Akt activation. Treatment of OASF with HG increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the VEGF promoter. CONCLUSIONS: Our results suggest that the HG increases VEGF expression in human synovial fibroblasts via the ROS, PI3K, Akt, c-Jun and AP-1 signaling pathway. GENERAL SIGNIFICANCE: We link high glucose on VEGF expression in osteoarthritis.

Risk Factors of Failed Conservative Treatment for Adjacent Vertebral Fractures Following Percutaneous Vertebroplasty.

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

Association of the Reduced Levels of Monocyte Chemoattractant Protein-1 with Herpes Zoster in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors in a Single-Center Cohort.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63-150.30 pg/mL versus 142.3 pg/mL, IQR 106.7-175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0-38.2 ng/mL versus 10.5 ng/mL, IQR 9.9-15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.

Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.

Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.

Ossification of posterior atlantoaxial membrane causing spinal stenosis - A case report.

Background: Ossification of the posterior atlantoaxial membrane (PAAM) is a rare cause of spinal cord compression. Case presentation: A 46-year-old woman with rheumatoid arthritis (RA) and a 2-year history of slowly progressive gait disturbance underwent surgery for right knee stiffness and right lower limb mild weakness. A neurologic examination revealed brisk deep tendon reflexes (DTR) and spasticity in her four limbs. A computed tomography (CT) scan revealed spinal stenosis caused by ossification of the PAAM, a rare cause of spinal cord compression. The patient's lower limbs weakness and walking capability were ameliorated post-surgery. Conclusions: Although the exact mechanism of ossification of PAAM remains unclear, chronic mechanical stress as well as persistent atlantoaxial instability may promote the development of the ossification.

A Streamlined Diagnostic Process Improved the Outcomes of Patients with Adult-Onset Still's Disease: A Single-Center Retrospective Observational Study.

INTRODUCTION: The diagnosis of adult-onset Still's disease (AOSD) is often delayed due to its clinical heterogeneity and lack of pathognomic features. Hence, there is an unmet need for an efficient diagnostic process. The major aim of this study was to compare the differences in disease outcomes between two groups of AOSD patients with and without implementation of the streamlined diagnostic process (SDP). METHODS: Of 172 febrile patients with skin rash and/or arthralgia, 112 individuals had AOSD. The tentative diagnosis of AOSD or non-AOSD was made with or without the SDP implementation. The selection criteria for AOSD outcomes analysis were as follows: (1) age at study entry older than 20 years, (2) fulfillment of the Yamaguchi criteria for AOSD diagnosis, and (3) a follow-up period longer than 6 months after initiation of therapy. Three outcome parameters were evaluated, including diagnosis lag period, the proportion of "early diagnosis," and the proportion of achieving disease remission after a 6-month therapy. RESULTS: The SDP was implemented for expediting AOSD diagnosis in 41 (36%) enrolled patients (SDP-implemented group). The diagnosis lag period was significantly shorter in the SDP-implemented group (median 2.0 weeks, interquartile range [IQR] 1.0-2.5 weeks) than in the non-SDP-implemented group (4.0 weeks, IQR 2.0-6.0 weeks, p < 0.001). A significantly higher proportion of "early diagnosis" was also found in the SDP-implemented group (75.6%) compared with the non-SDP-implemented group (33.8%, p < 0.001). We revealed a significantly higher proportion of achieving remission in the SDP-implemented group (85.4%) compared with the non-SDP-implemented group (67.6%, p < 0.05). Logistic regression analysis revealed SDP implementation as a potential predictor of achieving disease remission. CONCLUSIONS: Implementing an SDP for expediting diagnosis could improve outcomes for AOSD patients. This diagnostic process increased the early diagnosis rate and led to a higher disease remission rate. However, the beneficial effects of SDP implementation need further external validation.

Mirabegron is better tolerated than solifenacin in Sjogren's syndrome patients with overactive bladder symptoms-A randomized controlled trial.

OBJECTIVES: This study investigates the efficacy and adverse events of beta-3 agonists and antimuscarinic agents for managing overactive bladder syndrome in Sjogren syndrome. METHODS: Sjogren's syndrome patients with an Overactive Bladder Symptom Score (OABSS) >5 were enrolled and were randomly assigned to mirabegron 50 mg/day or solifenacin 5 mg/day. Patients were evaluated on the recruitment day and reassessed at Week 1, 2, 4, and 12. The study's primary endpoint was to have a significant change in OABSS at Week 12. The secondary endpoint was the adverse event and crossover rate. RESULTS: A total of 41 patients were included in the final analysis, with 24 in the mirabegron group and 17 in the solifenacin group. The study's primary outcome was a change of the OABSS at Week 12. We found that both mirabegron and solifenacin significantly reduce patients' OABSS after 12 weeks of treatment. The evolution of the OABSS was -3.08 for mirabegron and -3.71 for solifenacin (p = .56). Six out of 17 patients from the solifenacin group crossed over to the mirabegron arm due to severe dry mouth or constipation, while none from the mirabegron arm crossed over to the solifenacin group. Sjogren's syndrome-related pain was also improved in the mirabegron group (4.96-1.67, p = .008) compared to the solifenacin group (4.39-3.4, p = .49). CONCLUSIONS: Our study showed that mirabegron is equally effective as solifenacin in treating Sjogren's syndrome patients with overactive bladder. Mirabegron is superior to solifenacin in terms of treatment-related adverse events.

Association of toll-like receptor 9 gene polymorphism in Chinese patients with systemic lupus erythematosus in Taiwan.

The purpose of this study was to determine whether toll-like receptor 9 (TLR9) gene polymorphisms were markers of susceptibility to or severity of systemic lupus erythematosus (SLE) in Taiwanese patients. The study included 211 healthy individuals and 167 Chinese patients with SLE. Polymorphisms of TLR9 [rs2066807 and rs187084 (-1486 T/C)] were typed from genomic DNA. The genotypes, allelic frequencies, and carriage rates were compared between patients with SLE and control subjects. The relationship between allelic frequencies and clinical manifestations of 167 patients with SLE was evaluated. There was no statistically significant difference in TLR9 (rs2066807) gene polymorphism, allelic frequency, and carriage rate between the SLE and control groups. However, for the genotype of TLR9 -1486 T/C (rs187084) polymorphism, there was a statistically significant difference between the SLE and the control groups (P < 0.001, χ(2) = 15.9). Moreover, there was a significant association between the two groups in allelic frequency and carriage rate of the T allele (P < 0.001, χ(2) = 18.5 and P < 0.01, χ(2) = 8.06, respectively). We did not detect any association between the TLR9 genotype and the clinical or laboratory profiles in patients with SLE. The results suggest that the TLR9 -1486 T/C (rs187084), but not TLR9 (rs2066807), polymorphism is related to SLE in Taiwanese patients.

MBD4 gene is associated with rheumatoid arthritis in Chinese patients in Taiwan.

This study examines whether or not MBD4 polymorphism is a marker for rheumatoid arthritis (RA) susceptibility or severity for Chinese patients in Taiwan. This study included 193 patients with RA, while 190 unrelated healthy individuals living in Central Taiwan served as controls. The relationship between MBD4 polymorphism and clinical manifestations of RA was evaluated. For the genotype and allelic frequency of MBD4-1057 polymorphism, there were no statistically significant differences between patients with RA and controls. There were significant differences in the distribution of MBD4-8666 polymorphism frequencies between patients with RA and controls [P = 0.013; P (corrected) (Pc) = 0.039]. There were also significant relationships in the distribution of MBD4-9229 polymorphism genotype between patients with RA and controls (P = 0.007; Pc = 0.021). However, we did not detect any associations for MBD4-1057, MBD4-8666 or MBD4-9229 with rheumatoid factor presence, extra-articular involvement or bone erosion in patients with RA. Results suggest that MBD4-8666 and MBD4-9229, but not MBD4-1057, gene polymorphisms are related to RA in Chinese patients in Taiwan.

The Resistance Mechanisms and Clinical Impact of Resistance to the Third Generation Cephalosporins in Species of Enterobacter cloacae Complex in Taiwan.

Enterobacter cloacae complex (ECC) is ubiquitous in the environment and is an important pathogen causing nosocomial infections. Because routine methods used in clinical laboratories cannot identify species within ECC, the clinical significance of each species within ECC is less known. We applied hsp60 gene sequencing to identify the species/clusters of ECC and detected ß-lactamase genes and class 1 integrons with PCR for 184 clinical ECC isolates in Taiwan from 2013 to 2014 to investigate the clinical impact of species within ECC. The four most common clusters were E. hormaechei subsp. steigerwaltii (cluster VIII) (29.9%), E. hormaechei subsp. oharae (cluster VI) (20.1%), E. cloacae subsp. cloacae (cluster XI) (12%), and E. kobei (cluster II) (10.3%). E. hormaechei, which consisted of four clusters (clusters III, VI, VII, and VIII), is the predominant species and accounted for 57.1% of the isolates. The ceftazidime resistance rate was 27.2%, and the ceftriaxone resistance rate was 29.3%. Resistance to third generation cephalosporin was associated with a higher 30-day mortality rate. In total, 5 (2.7%), 24 (13.0%), and 1 (0.5%) isolates carried ESBL, AmpC, and carbapenemase genes, respectively. Class 1 integrons were present in 24.5% of the isolates, and most of the cassettes pertain to antibiotic resistance. Resistance to third generation cephalosporins, multidrug resistance, and class 1 integrons were significantly more in E. hormaechei (clusters III, VI, VII, and VIII) than in the other species. The 30-day mortality rate and 100-day mortality did not differ significantly between patients with E. hormaechei and those with infections with the other species. In conclusion, the distribution of third generation cephalosporin resistance, multidrug resistance, and class 1 integrons were uneven among Enterobacter species. The resistance to third generation cephalosporins possessed significant impact on patient outcome.

Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem-Nonsusceptible Enterobacter cloacae Complex Infections in a Taiwan University Hospital.

The genus Enterobacter is a member of the ESKAPE group, which contains the major resistant bacterial pathogens. Enterobacter cloacae complex (ECC) has emerged as a clinically significant cause of a wide variety of nosocomial infections. Carbapenem-nonsusceptible Enterobacter cloacae complex (CnsECC) has become an emerging threat to public health but there is still a lack of comprehensive molecular and clinical epidemiological analysis. A total of 157 CnsECC isolates were recovered during October 2011 to August 2017. hsp60 gene sequencing and pulsed-field gel electrophoresis (PFGE) were applied to discriminate the species, genetic clusters and clonal relatedness. All the isolates were subjected to polymerase chain reaction (PCR) analysis for carbapenemase, AmpC-type ß-lactamase, and extended spectrum ß-lactamase (ESBL) genes. Clinical data were collected on all patients for comparing clinical risks and outcomes between patients with carbapenemase-producing (CP)-CnsECC compared with non-CP-CnsECC infection. The most commonly identified species was E. hormaechei subsp. hoffmannii (47.1%), followed by E. hormaechei subsp. steigerwaltii (24.8%). Different species of CnsECC isolates showed heterogeneity in resistance patterns to piperacillin/tazobactam, cefepime and levofloxacin. In the present study, we observed that E. hormaechei subsp. hoffmannii was characterized with higher cefepime and levofloxacin resistance rate but lower piperacillin/tazobactam resistance rate relative to other species of CnsECC. CP-CnsECC comprised 41.1% (65 isolates) and all of these isolates carried IMP-8. In this study, 98% of patients had antimicrobial therapy prior to culture, with a total of 57/150 (38%) patients being exposed to carbapenems. Chronic pulmonary disease (OR: 2.51, 95% CI: 1.25-5.06), received ventilator support (OR: 5.54, 95% CI: 2.25-12.03), steroid exposure (OR: 3.88, 95% CI: 1.91-7.88) and carbapenems exposure (OR: 2.17, 95% CI: 1.10-4.25) were considered risk factors associated with CP-CnsECC infection. The results suggest that CP-CnsECC are associated with poorer outcomes including in-hospital mortality, 30-day mortality and 100-day mortality. Our study provides insights into the epidemic potential of IMP-8-producing E. cloacae for healthcare-associated infections and underscores the importance of understanding underlying resistance mechanisms of CnsECC to direct antibiotic treatment decisions.

Hypothyroidism risk associated with rheumatoid arthritis: A population-based retrospective cohort study.

ABSTRACT: Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities.We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated.The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person-years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39-2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person-years in 20 to 39 years to 20.0 per 1000 person-years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person-years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24-12.0).RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.

The effectiveness of tocilizumab in treating refractory adult-onset Still's disease with dichotomous phenotypes: IL-18 is a potential predictor of therapeutic response.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration. METHODS: This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method. RESULTS: Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28 < 2.6) at weeks 12, 24, 36, and 48, respectively, among articular subtype patients. The systemic activity scores and inflammatory parameters were significantly decreased after 12-week TCZ therapy, and TCZ could significantly reduce corticosteroid dose in AOSD patients. Multivariate analysis reveals that baseline IL-18 level is a significant predictor of poor therapeutic response at week 24 (odds ratio 7.86, p < 0.05). CONCLUSION: AOSD patients refractory to high-dose corticosteroids and methotrexate may respond well to TCZ treatment with a steroid-sparing effect and an acceptable safety. A high baseline IL-18 level may be a predictor of poor therapeutic response. Key Points • Tocilizumab may be effective and well-tolerated in refractory AOSD patients regardless of disease subtypes. • High plasma levels of IL-18 may predict poor response to tocilizumab in AOSD patients.

Improved nasal recovery and intact olfactory function after a transseptal approach for endoscopic endonasal transsphenoidal adenomectomy: A retrospective analysis.

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22-item sinonasal outcome tests (SNOT-22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT-22 and Lund-Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT-22 scores and Lund-Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b.

Exploring RNA modifications, editing, and splicing changes in hyperuricemia and gout.

Hyperuricemia and gout are two of the most common metabolic disorders worldwide; their incidence is increasing with changes in lifestyle, and they are correlated with many diseases, including renal and cardiovascular diseases. The majority of studies on hyperuricemia and gout have focused on the discovery of the associated genes and their functions and on the roles of monocytes and neutrophils in the development of gout. Virtually no studies investigating the epigenomics of gout disease or exploring the clinical significance of such research have been conducted. In this study, we observed that the expression of enzymes involved in RNA modifications or RNA editing was affected in uric acid (UA)- or monosodium urate (MSU)-treated cell lines. RNA alternative splicing and splicing factors were also affected by UA or MSU treatment. We used transcriptome sequencing to analyze genome-wide RNA splicing and RNA editing and found significant changes in RNA splicing and RNA editing in MSU- or UA-treated THP-1 and HEK293 cells. We further found significant changes of RNA modifications, editing, and splicing in patients with gout. The data indicate that RNA modifications, editing, and splicing play roles in gout. The findings of this study may help to understand the mechanism of RNA splicing and modifications in gout, facilitating the development of new diagnostic and therapeutic strategies.

The Impact of b/tsDMARD Dose Reduction on Chronic Hepatitis B in Rheumatoid Arthritis Patients: A Two-Center Long-Term Safety Analysis.

BACKGROUND: We aimed to investigate the change of hepatitis B virus (HBV) viral loads and HBV reactivation (HBVr) in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). METHODS: This two-center analysis retrospectively investigated the virological and biochemical evidence of HBVr in RA patients who underwent b/tsDMARD dose reduction. Serum levels of viral loads were determined using real-time PCR. Serum levels of alanine transaminase (ALT) were determined using spectrophotometry. RESULTS: Among a total of 40 HBsAg+ RA patients who tapered b/tsDMARDs, 14 (35%) used tocilizumab; 12 (30%) used tumor necrosis factor (TNF)-α inhibitors; and the rest used either abatacept or tofacitinib. We found that patients who had detectable HBV DNA before tapering achieved a one-log reduction in HBV DNA levels, in contrast to the findings in the other 12 patients who did not taper b/tsDMARDs (no change in HBV DNA levels with time). The incidence of HBVr (increased viral loads with hepatitis) was 4.62 (95%CI: 2.08, 10.28) and 2.26 (95%CI: 0.56, 9.02) events per 100 person-years before and after b/tsDMARD tapering, respectively. CONCLUSIONS: The HBV viral load decreased after the tapering of b/tsDMARDs in RA patients with detectable HBV DNA. Dose reduction in b/tsDMARDs might be beneficial.

Prognostic significance of lab data and performance comparison by validating survival prediction models for patients with spinal metastases after radiotherapy.

BACKGROUND AND PURPOSE: Well-performing survival prediction models (SPMs) help patients and healthcare professionals to choose treatment aligning with prognosis. This retrospective study aims to investigate the prognostic impacts of laboratory data and to compare the performances of Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy (METSSS) model, New England Spinal Metastasis Score (NESMS), and Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) for spinal metastases (SM). MATERIALS AND METHODS: From 2010 to 2018, patients who received radiotherapy (RT) for SM at a tertiary center were enrolled and the data were retrospectively collected. Multivariate logistic and Cox-proportional-hazard regression analyses were used to assess the association between laboratory values and survival. The area under receiver-operating characteristics curve (AUROC), calibration analysis, Brier score, and decision curve analysis were used to evaluate the performance of SPMs. RESULTS: A total of 2786 patients were included for analysis. The 90-day and 1-year survival rates after RT were 70.4% and 35.7%, respectively. Higher albumin, hemoglobin, or lymphocyte count were associated with better survival, while higher alkaline phosphatase, white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or international normalized ratio were associated with poor prognosis. SORG-MLA has the best discrimination (AUROC 90-day, 0.78; 1-year 0.76), best calibrations, and the lowest Brier score (90-day 0.16; 1-year 0.18). The decision curve of SORG-MLA is above the other two competing models with threshold probabilities from 0.1 to 0.8. CONCLUSION: Laboratory data are of prognostic significance in survival prediction after RT for SM. Machine learning-based model SORG-MLA outperforms statistical regression-based model METSSS model and NESMS in survival predictions.