Effects of Rotavirus Vaccination Coverage among Infants on Hospital Admission for Gastroenteritis across All Age Groups, Japan, 2011-2019.

We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011-2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage <40% (e.g., for coverage >80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83-0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.

Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity.

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (n = 10), matched siblings (n = 2), and unrelated bone marrow donors (n = 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3-4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4+ T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words).

Impact of prophylactic echinocandin on the development of neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation: A single-center retrospective study.

BACKGROUND: Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. METHODS: We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). RESULTS: Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. CONCLUSION: Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.

Etiology and clinical course of severe and extreme thrombocytosis in children: a retrospective single-center study.

The aim of this study was to describe the etiology and clinical course in children with severe thrombocytosis (ST, platelet counts > 900 × 109/L) and extreme thrombocytosis (ET, platelet counts > 1000 × 109/L) in a tertiary pediatric hospital. Patients aged 0-18 years with platelet counts over 900 × 109/L who were admitted to our hospital were analyzed. Thrombocytosis was defined as a platelet count exceeding 450 × 109/L. Thrombosis was diagnosed based on computed tomography scans or ultrasound findings. Potential factors associated with the development of extreme thrombocytosis were identified using logistic regression models. Only one (0.8%) out of the 120 patients identified with ST (n = 61) and ET (n = 59) had primary thrombocytosis. The most common underlying condition was congenital heart disease (26.7%), followed by Kawasaki disease (16.7%). With the exception of the hemoglobin level, no major differences were found for the baseline characteristics between the ST and ET groups. A lower hemoglobin level (< 10.0 g/dL) at the onset of thrombocytosis was identified as a predictor for ET development (adjusted odds ratio 2.73, 95% confidence interval 1.18-6.28). Overall, 56 of 120 (46.7%) patients received aspirin therapy. Venous thrombosis occurred in one (0.8%) patient. CONCLUSIONS: We found a low proportion of primary thrombocytosis and a low incidence of thrombosis in children with ST and ET. Our results suggest that pediatric ST and ET may share common characteristics and may have features that are distinct from those in adults. WHAT IS KNOWN: • Secondary thrombocytosis is a frequent finding in children. • Adult extreme thrombocytosis has been found to be associated with primary thrombocytosis. WHAT IS NEW: • There were no major differences in the baseline characteristics between children with severe and extreme thrombocytosis. • The incidence of thrombosis was markedly low in both severe and extreme thrombocytosis groups.

Clinical features of juvenile onset ankylosing spondylitis in Japanese patients.

OBJECTIVES: This retrospective study aimed to examine the clinical features of juvenile onset ankylosing spondylitis (JoAS) in Japanese patients. METHODS: We examined clinical symptoms (including initial symptoms) and the progression to diagnosis of AS in 17 Japanese JoAS patients at our institute between January 2004 and May 2023. Initial symptoms were considered pain at axial joints and/or extra-axial joints. RESULTS: Mean ages (± standard deviation) at onset and diagnosis of AS were 12.9 (± 2.0) years and 19.6 (± 9.6) years, respectively. The back was the most common site of initial symptoms (seven patients; 41.2%), followed by the hip (five patients; 29.4%) and knees (five patients; 29.4%). Initial symptoms were limited to extra-axial joints and axial joints in nine (52.9%) and seven (41.2%) patients, respectively. Nine patients (52.9%) were recognised as a musculoskeletal disease other than AS, such as oligoarticular juvenile idiopathic arthritis. CONCLUSIONS: Sites of initial symptoms were frequently the back, hip, and knees, with 52.9% of patients having initial symptoms limited to extra-axial joints. More than half of the patients were recognised musculoskeletal diseases other than AS.

Intervertebral fusion sites in patients with ankylosing spondylitis: A computed tomography study.

OBJECTIVES: To examine intervertebral fusion sites along the whole spine of patients with ankylosing spondylitis using computed tomography. METHODS: This retrospective study examined intervertebral fusion of five sites (anterior/posterior vertebrae, left/right zygapophyseal joints, and spinous process) on 23 vertebrae in the cervical, thoracic, and lumbar regions of the spine in 40 patients diagnosed with ankylosing spondylitis at our institute between January 2004 and December 2022. RESULTS: Mean age [± standard deviation (SD)] was 40.5 (± 17) years, and mean disease duration (± SD) was 11.4 (± 10.5) years at computed tomography evaluation; 55.9% were human leukocyte antigen B-27-positive. Fifteen (37.5%) patients showed intervertebral fusion in the thoracic and/or cervical regions, but not in the lumbar region. Fusion of posterior vertebrae was observed most frequently in the thoracic region, compared to the cervical and lumbar regions. In particular, more than half of the patients showed fusion of posterior vertebrae Th4-Th5 to Th7-Th8. CONCLUSIONS: In 37.5% of patients, intervertebral fusion was evident in the thoracic and/or cervical regions but not in the lumbar region. The most common site and region of intervertebral fusion were the posterior vertebrae of the middle thoracic region.

Incidence and Causative Organisms of Bacteriuria in Children With Cancer: A 9-Year Experience in a Tertiary Pediatric Center.

Although infection is common in patients with cancer, the distribution of causative agents and the proportion of resistant bacteria in patients with urinary tract infection remain unknown. The aim of this study was to describe the incidence, the causative agents, and the proportion of antimicrobial resistance in bacteria cultured from urine of hospitalized children with cancer. A single-center retrospective chart review of patients with cancer admitted between 2012 and 2020 was performed to identify patients with positive urine culture. Overall, 61 (0.9%) of 7107 patients were identified to have positive urine cultures. Among them, 25 patients (41%) had symptomatic bacteriuria. The most common pathogenic bacterium among all patients was Escherichia coli ( E. coli ) (n=15, 25%), followed by Enterococcus sp. (n=14, 23%), Klebsiella sp. (n=12, 20%), and Pseudomonas aeruginosa ( P. aeruginosa ) (n=12, 20%). Extended spectrum ß-lactamases-producing E. coli and Extended spectrum ß-lactamases-producing Klebsiella pneumoniae were detected in 1 patient (2%) and 4 patients (7%), respectively. No multidrug-resistant P. aeruginosa and vancomycin-resistant Enterococcus were detected. The incidence of bacteriuria was found to be low in children with cancer. The distribution of causative agents of bacteriuria in children with solid tumors and hematologic diseases may be different from that in previously healthy children.

Sacroiliac joint fusion in patients with ankylosing spondylitis is associated with hip involvement.

OBJECTIVE: Ankylosing spondylitis (AS) is a progressive inflammatory disease that affects the axial skeleton, and often associated with hip involvement. However, the causative factors for radiological hip involvement in patients with AS are not well characterized. This study aimed to investigate the factors associated with hip involvement in patients with AS. METHODS: Sixty-seven patients (134 hips) diagnosed with AS who qualified the modified New York criteria at our institution between January 2005 and June 2022 were enrolled. Patients were divided into two groups: the hip involvement group (BASRI-hip score ≥2 points) and the normal group (BASRI-hip score <2 points). Demographic, clinical and radiographic characteristics were compared between the two groups. RESULTS: Twenty-six patients (38.8%) had radiological hip involvement, of which 23 (88.5%) patients were male. There were significant between-group differences with respect to sacroiliac joint fusion, crossover sign, high centre edge angle and low sharp angle (P < 0.05). On logistic regression analysis, older age, sacroiliac joint fusion and pincer type were identified as independent risk factors for hip involvement. CONCLUSION: AS with hip involvement was significantly more likely to involve sacroiliac joint fusion, which suggested that mechanical stress in adjacent joints and reduced spinopelvic range of motion may influence hip involvement.

Increased prevalence of Staphylococcus aureus nasal carriage in rheumatoid arthritis patients with moderate/high disease activity.

BACKGROUND: Staphylococcus aureus (S. aureus) nasal carriage is a well-known risk factor for surgical site infection (SSI) after total joint arthroplasty. This study aimed to compare the prevalence of S. aureus nasal carriage between patients with osteoarthritis (OA), a degenerative joint disease, and those with rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, who underwent total joint arthroplasty, and to investigate the influence of RA disease activity on nasal carriage rate. METHODS: This retrospective study targeted 508 OA and 107 RA patients who underwent S. aureus nasal screening prior to primary total knee and/or hip arthroplasty. RA patients were divided into two groups based on disease activity: the remission/low disease activity (REM/LDA) group and the moderate/high disease activity (MDA/HDA) group. Factors associated with S. aureus nasal carriage were assessed with multivariate logistic regression models. RESULTS: Of all 615 patients, 155 (25%) carried S. aureus in their nares. Compared to OA patients, RA patients had a significantly higher rate of S. aureus nasal carriage (24% vs. 33%, p = 0.049). Compared to the REM/LDA group (n = 39), the MDA/HDA group (n = 58) had a significantly higher rate of S. aureus nasal carriage (21% vs. 41%, p = 0.032). Multivariate analysis revealed that the MDA/HDA group, but not the REM/LDA group, had a significantly higher odds of S. aureus nasal carriage compared to the OA group (odds ratio: 2.76, 95% confidence interval: 1.07-7.12). CONCLUSION: Preoperative nasal screening for S. aureus is beneficial, especially in RA patients with moderate/high disease activity.

Associations of frailty with RA-ILD and poor control of disease activity in patients with rheumatoid arthritis: A multi-center retrospective observational study.

BACKGROUND: This study aimed to investigate factors associated with frailty in rheumatoid arthritis (RA) patients. METHODS: A total of 656 RA patients were evaluated using data from an observational study in 2022. Among these patients, 152 with frailty were assigned to the frailty group, and 504 without frailty were assigned to the non-frailty group. Patient characteristics were compared between the two groups by univariate analysis, and factors associated with frailty were assessed by logistic regression analysis. Patient characteristics were also compared between patients with RA-associated interstitial lung disease (RA-ILD) (n = 102) and those without RA-ILD (n = 554). RESULTS: The frailty group was older (mean: 73.6 vs. 66.8 years) and had a higher DAS28-ESR (3.67 vs. 2.66), a higher HAQ-DI (1.13 vs. 0.32), and a higher rate of RA-ILD (25.0 vs. 12.7 %) than the non-frailty group. Age (OR: 1.03, 95 % CI: 1.01-1.05), HAQ-DI (3.22, 2.28-4.56), DAS28-ESR (1.44, 1.19-1.75), and RA-ILD (2.21, 1.24-3.94) were associated with frailty. RA patients with RA-ILD were older (73.3 vs. 67.5 years) and had a higher DAS28-ESR (3.30 vs. 2.80), a higher HAQ-DI (1.19 vs. 0.32), a higher proportion of frail patients (37.3 vs. 20.6 %), lower MTX use (26.5 vs. 62.9 %), and higher steroid use (44.1 vs. 26.8 %) than those without RA-ILD. CONCLUSIONS: Maintaining reasonable control of disease activity is necessary for RA patients, including those with RA-ILD, to recover from frailty.

Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J).

OBJECTIVE: Various guidelines recommend that patients with early rheumatoid arthritis (RA) try to achieve clinical remission within 6 months, and early therapeutic intervention is important to this end. This study aimed to investigate short-term treatment outcomes of patients with early-diagnosed RA in clinical practice and to examine predictive factors for achieving remission. METHODS: Of the 210 patients enrolled in the multicenter RA inception cohort, 172 patients who were followed up to 6 months after treatment initiation (baseline) were included. Logistic regression analysis was used to examine the impact of baseline characteristics on achievement of Boolean remission at 6 months. RESULTS: Participants (mean age, 62 years) initiated treatment after a mean of 19 days from RA diagnosis. At baseline and 3 and 6 months after treatment initiation, proportions of patients using methotrexate (MTX) were 87.8%, 89.0%, and 88.3%, respectively, and rates of Boolean remission were 1.8%, 27.8%, and 34.5%, respectively. Multivariate analysis revealed that physician global assessment (PhGA) (Odds ratio (OR): 0.84, 95% confidence interval (CI): 0.71-0.99) and glucocorticoid use (OR: 0.26, 95% CI: 0.10-0.65) at baseline were independent factors that predicted Boolean remission at 6 months. CONCLUSION: After a diagnosis of RA, satisfactory therapeutic effects were achieved at 6 months after the initiation of treatment centered on MTX according to the treat to target strategy. PhGA and glucocorticoid use at treatment initiation are useful for predicting the achievement of treatment goals.

Age and symptoms at onset of ankylosing spondylitis in Japanese patients.

OBJECTIVES: To examine the age at onset and initial symptoms as clinical features of ankylosing spondylitis in Japanese patients. METHODS: This retrospective study included 60 Japanese patients diagnosed with ankylosing spondylitis at our institute between January 2004 and June 2021. Initial symptoms were considered pain in axial joints and/or extra-axial joints. If a patient had initial symptoms at multiple sites, each site was counted. We assessed trends for the number of patients and sites of initial symptoms according to age at onset. RESULTS: Mean age (± standard deviation) at onset was 28.9 (± 14.3) years. Approximately one-third of patients experienced onset before age 20. The back was the most common site of initial symptoms (36.7%), followed by the hip (26.7%), knee (15%), buttocks (15%), neck (10%), finger (6.7%), shoulder (3.3%), and others (including overlapping sites). Thirty-two (53.3%) and 25 (41.7%) patients had initial symptoms only in axial joints and only in extra-axial joints, respectively. The proportion of patients with initial symptoms only in extra-axial joints significantly decreased with increasing age (p = .024). CONCLUSIONS: Sites of initial symptoms were frequently the back, hip, knee, and buttocks, and 41.7% had initial symptoms only in extra-axial joints. Younger onset patients frequently had extra-axial involvement.

Factors associated with frailty in rheumatoid arthritis patients with decreased renal function.

OBJECTIVES: To investigate factors associated with frailty in rheumatoid arthritis (RA) patients with decreased renal function. METHODS: RA patients who visited outpatient clinics from June to August 2021 were included (N = 625). Patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 were defined as having decreased renal function (N = 221) and divided into the non-frailty (N = 153) and frailty (N = 58) groups. Patient characteristics were compared between the two groups by univariate analysis. Significant factors in univariate analysis were assessed by logistic regression analysis to determine their association with frailty in patients with decreased renal function. RESULTS: Patients in the frailty group were older (74.0 vs.79.0 years) and had a longer duration of disease (11.1 vs. 17.8 years), higher Disease Activity Score erythrocyte sedimentation rate (DAS28-ESR; 2.99 vs. 3.80), higher Health Assessment Questionnaire Disability Index (0.42 vs. 1.43), and a lower rate of methotrexate (MTX) use (46.4% vs. 25.9) compared to those in the non-frailty group. Factors associated with frailty in patients with decreased renal function were age (odds ratio: 1.07), duration of disease (1.06), DAS28-ESR (1.85), and MTX use (0.42). CONCLUSIONS: Among factors associated with frailty in RA patients with decreased renal function, improving DAS28-ESR is likely to be the most feasible approach to promote recovery from frailty (200/200 words).

Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

OBJECTIVES: The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. METHODS: 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. RESULTS: Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23-0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30-0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. CONCLUSIONS: Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

Reasons and risk factors for discontinuation of treatment with any biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A long-term observational study.

OBJECTIVES: Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. METHODS: The study included 564 patients with RA who started bDMARDs treatment before 2008 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models. RESULTS: Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3-4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07-6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years. CONCLUSIONS: Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

Poorly Differentiated Chordoma of the Clivus With Loss of SMARCB1 Expression in a Pediatric Patient: A Case Report.

Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.

Disease activity at baseline is an independent predictor of frailty at one year in pre-frail patients with rheumatoid arthritis; a multicenter retrospective observational study.

OBJECTIVES: To investigate factors predicting frailty for one year in pre-frail patients with rheumatoid arthritis (RA). METHOD: A total of 298 RA patients who were pre-frail in 2020 were evaluated in this structured, retrospective observational study. Of the 298 patients, 42 who were frail and 256 who were not in 2021 were assigned to the frailty and non-frailty groups, respectively. After comparing characteristics of both groups using univariate analysis, predictive factors of frailty were assessed by logistic regression analysis. The proportion of frail patients in 2021 by DAS28-ESR level in 2020 was examined by the Cochran-Armitage trend test and chi-squared test. After dividing pre-frail patients into those with DAS28-ESR ≥3.2 and DAS28-ESR <3.2 in 2020, one-year change in DAS28-ESR in the frailty and non-frailty groups for both subgroups were compared by the paired t-test. RESULTS: The frailty group was older (mean: 71.0 vs. 65.4 years) and had a higher DAS28-ESR (mean: 3.22 vs. 2.70) than the non-frailty group. DAS28-ESR was identified as a predictive factor for frailty (OR: 1.49). Among patients with DAS28-ESR ≥3.2 in 2020, DAS28-ESR improved in the non-frailty group in 2021 (mean: 3.97 in 2020 vs. 3.13 in 2021) but did not in the frailty group (3.97 in 2020 vs. 3.81 in 2021). Among those with DAS28-ESR <3.2 in 2020, DAS28-ESR was unchanged in the non-frailty group in 2021 (2.15 in 2020 vs. 2.23 in 2021) but increased in the frailty group (2.53 in 2020 vs. 3.23 in 2021). CONCLUSIONS: Disease activity at baseline is an independent predictor of frailty one year later in pre-frail patients with RA.

Relationship between locomotive syndrome and frailty in rheumatoid arthritis patients by locomotive syndrome stage.

OBJECTIVES: This study aimed to evaluate the association between locomotive syndrome (LS) and frailty in rheumatoid arthritis (RA) patients. METHODS: Subjects were 538 RA patients (female, 72.9%; mean age ± standard deviation, 66.8 ± 13.4 years). LS and frailty were defined as ≥16 points on the 25-question Geriatric Locomotive Function Scale (Stage ≥2) and ≥8 points on the Kihon Checklist (KCL), respectively. RESULTS: There were 214 subjects with Stage ≥2 LS (39.8%) and 213 subjects with frailty (39.6%). Among subjects with Stage 0, 1, 2, and 3 LS, 11.0%, 21.9%, 48.3%, and 84.6% had frailty, respectively. The KCL points for cognitive and psychosocial factors had no significant differences across LS stages. Multivariable logistic regression analysis revealed that the Health Assessment Questionnaire was independently associated with frailty and LS stage, and the Clinical Disease Activity Index was associated with LS stage but not frailty. CONCLUSIONS: As LS worsens in RA patients, the likelihood of developing physical frailty increases. RA patients with a low LS stage can still develop frailty, and suppressing disease activity may not be sufficient to prevent frailty. These findings highlight the need to screen for frailty in RA patients and consider appropriate interventions based on each patient's condition, focusing on nonphysical factors.

Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphorylation in the anti-inflammatory effect of 2-deoxyglucose.

The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. But, changes in the metabolism of normal synovial membranes or synovial cells during the early stages of inflammation remains unknown. Moreover, there are still many aspects of inflammatory signaling pathways altered by glycolysis inhibitors, that remain unclear. In this study we found that, in normal, non-pathological bovine synovial cells, most of ATP synthesis was generated by mitochondrial respiration. However, during the early of stages inflammation, initiated by lipopolysaccharide (LPS) exposure, synovial cells shifted to glycolysis for ATP production. The glycolysis inhibitor 2-deoxyglucose (2DG) reversed LPS induced increases in glycolysis for ATP production and suppressed the expression of inflammatory cytokines and proteolytic enzymes. 2DG suppressed the phosphorylation of the transcription factor cAMP response element binding protein (CREB) enhanced by LPS. Treatment with a CREB inhibitor reversed the expression of LPS-stimulated inflammatory cytokines and proteolytic enzymes. This study showed that changes in metabolism occur during the early stages of inflammation of synovial cells and can be reversed by 2DG and signaling pathways associated with CREB phosphorylation.

Paranasal sinusitis at the initiation of chemotherapy is a risk factor for invasive fungal disease in children and adolescents with cancer.

BACKGROUND: The impact of paranasal sinusitis on the clinical outcome of patients with cancer remains unknown. The aim of this study was to determine whether paranasal sinusitis at the initiation of chemotherapy (SAI) affects the development of infectious complications in children and adolescents with cancer. METHODS: A retrospective cohort analysis of patients aged 0-20 years with cancer who received chemotherapy was performed. SAI was defined as the presence of a fluid level or mucosal swelling or total opacity on sinus computed tomography examination before the initiation of chemotherapy. The primary outcome measures were the incidence of bacteremia, septic shock, and invasive fungal disease (IFD, including proven, probable, and possible cases). RESULTS: SAI was observed in 57 (44%) of 130 enrolled patients. There were no significant differences in age, sex, and disease distribution between the patients with SAI (SAI group) and those without (non-SAI group). There was no significant difference in the 1-year cumulative incidence of bacteremia or septic shock after treatment initiation between the two groups (bacteremia, SAI group 33% vs. non-SAI group 35%, P = 0.53; septic shock, SAI group 4% vs. non-SAI group 4%, P = 0.87). The 1-year cumulative incidence of IFD was higher in the SAI group than in the non-SAI group (22% vs. 6%, P = 0.012). Cumulative incidence analysis after inverse probability of treatment weighting adjustment showed that the SAI group was more likely to develop IFD (HR: 3.5, 95% CI: 1.1-11.2, P = 0.033). CONCLUSIONS: Our findings suggest that patients with SAI may be at higher risk for IFD during chemotherapy.