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This article discusses the relationship between locomotive syndrome (LS) and large joint symptoms in patients with rheumatoid arthritis (RA). LS refers to a condition that limits mobility due to musculoskeletal disorders and can lead to being bedridden. The study found that RA patients with large joint symptoms, especially in the lower limbs, were more likely to develop LS. The prevalence of LS was higher among RA patients compared to the general Japanese population. The findings suggest that addressing large joint symptoms in RA patients may help prevent LS and improve their quality of life. The study also highlights the importance of prompt treatment for large joint disabilities, including drug treatment and surgical options, in preventing LS in RA patients. Additionally, age, particularly in early-onset RA patients, is a significant factor related to LS. [Extracted from the article]

Objectives: To investigate a plateau in treatment enhancement for improving the frailty status of rheumatoid arthritis (RA) patients. Methods: A total of 345 RA patients who were not robust in 2021 were assigned to the improved ("robust 2022," n = 51) and non‐improved ("pre‐frailty/frailty 2022," n = 294) groups. Factors associated with "robust 2022" were examined by logistic regression analysis. Patients were assigned to the stable (Follow‐up mean DAS28‐ESR in 2020 and 2021 < 3.2, n = 225) and unstable (≥3.2, n = 120) groups, which were further divided into the non‐improved (stable: n = 180, unstable: n = 114) and improved (stable: n = 45, unstable: n = 6) groups. Factors influencing Japanese Cardiovascular Health Study (J‐CHS) score were examined by multiple regression analysis. Changes over 2 years were compared between the non‐improved and improved groups of the stable group. Results: The associated factor of "robust 2022" was the follow‐up meanDAS28‐ESR in 2020 and 2021 < 3.2 (i.e., stable state) (OR: 4.01). Follow‐up mean DAS28‐ESR in 2020 and 2021 was associated with J‐CHS score (T = 2.536, p =.013) only in the unstable group. In the stable group, HAQ‐DI was lower (2020: 0.32 vs. 0.16; 2021: 0.32 vs. 0.17; 2022: 0.32 vs. 0.21), and the proportion of J‐CHS: Q4 (weakness) was lower (2020: 48.4 vs. 17.8%; 2021: 55.0 vs. 29.2%; 2022: 50.4 vs. 0%), in the improved group than in the non‐improved group, whereas both groups maintained clinical and functional remission over 2 years. Conclusions: Drug treatment to maintain well‐controlled disease activity alone is insufficient for improving patients' frailty status after achieving treat‐to‐target goals, suggesting the need for multifaceted approaches. [ABSTRACT FROM AUTHOR]

Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila (A. m.), a mucin‐degrading bacterium, rapidly activate BM myelopoiesis and slow but long‐lasting hepato‐splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m. is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)‐1α, and in turn, activates IL‐1 receptor (IL‐1R)‐expressing splenic HSPCs. Genetic deletion of Toll‐like receptor‐2 and ‐4 (TLR2/4) or IL‐1α partially diminishes A. m.‐induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL‐1R‐ and TLR‐mediated signals regulate commensal bacteria‐driven EMH, which might be relevant for certain autoimmune disorders. Synopsis: A single injection of Akkermansia muciniphila, one of the major mucin‐degrading microbial species in the human gut, induces long‐lasting hepatosplenomegaly with splenic extramedullary hematopoiesis (EMH) by activating cooperative IL‐1R‐ and TLR‐mediated innate immune pathways.Injection of A. muciniphila lysate induces long‐lasting anemia and hepatosplenomegaly with expansion of functional HSCs.Cell expansion in the spleen is mediated by partially TLR2/4‐dependent and entirely MYD88/TRIF‐dependent pathways.Sustained secretion of IL‐1α from splenic myeloid cells contributes to TLR2/4‐independent EMH.Pharmacological inhibition of IL‐1R in addition to genetic ablation of TLR2/4 can completely alleviate induced EMH. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess the clinical outcomes following combined treatment with pembrolizumab and axitinib as first‐line therapy for patients with advanced RCC. Methods: This study retrospectively included 47 consecutive Japanese patients who were diagnosed with advanced RCC and subsequently received pembrolizumab and axitinib between February 2020 and January 2022. Efficacy and safety of this combined therapy in these patients were comprehensively investigated. Results: The 47 included patients were classified into the following 3 groups by the IMDC system: favorable, 7 (14.9%); intermediate, 24 (51.1%) and poor, 16 (34.0%). Responses to this combined therapy in the 47 patients were as follows: CR, 8 (17.0%); PR, 20 (42.6%); SD, 16 (34.0%) and PD, 3 (6.4%); thus, the ORR was 59.6%. During the observation period, disease progression and death occurred in 19 (40.4%) and 9 (19.1%) patients, respectively, and the median PFS and OS were 18 months and not reached, respectively. Univariate analyses identified the following significant predictors for poor prognostic outcomes: lack of nephrectomy, liver metastasis, bone metastasis, elevated CRP and IMDC poor risk for PFS; and lack of nephrectomy, non‐CCC and elevated CRP for OS. AEs and those corresponding to grade ≥ 3 occurred in all (100%) and 30 (63.8%) patients, respectively. Conclusions: To our knowledge, this is the first study focusing on real‐world outcomes following pembrolizumab and axitinib for treatment‐naïve advanced Japanese RCC patients, which showed the efficacy and safety of this combined therapy being similar or even superior to those in clinical trial. [ABSTRACT FROM AUTHOR]

Objectives: The present study comprehensively investigated the significance of several factors reflecting the therapeutic effects of anticancer treatment on overall survival (OS) in advanced urothelial cancer (UC) patients receiving sequential systemic therapy. Methods: This study included 101 consecutive advanced UC patients who received first‐line platinum‐based combination chemotherapy followed by second‐line pembrolizumab. The impacts of the following factors on OS in these patients were analyzed: responses to chemotherapy, responses to pembrolizumab, progression‐free survival (PFS) with chemotherapy, PFS with pembrolizumab, and second PFS (PFS2). Results: The median age of patients was 71 years, and 35 and 66 had UC in the upper urinary tract and bladder, respectively. objective response rate to first‐line chemotherapy and second‐line pembrolizumab were 37.6% and 19.8%, respectively. Median PFS with chemotherapy, pembrolizumab, and PFS2 were 5, 4, and 9 months, respectively. Uni‐ and multivariate analyses of the five factors examined identified PFS with pembrolizumab and PFS2 as independent surrogates for OS, with PFS2 (hazard ratio [HR] = 0.23) being more closely associated with OS than PFS with pembrolizumab (HR = 0.31). Furthermore, uni‐ and multivariate analyses of various prognostic parameters showed the independent impacts of baseline performance status (PS) and neutrophil‐to‐lymphocyte ratio (NLR) on PFS2. Conclusions: The present results suggest the potential of PFS2 as an optimal surrogate for OS in advanced UC patients receiving standard sequential systemic therapy and indicate that intensive treatment needs to be considered for those with poor PS and/or high NLR prior to the introduction of first‐line chemotherapy. [ABSTRACT FROM AUTHOR]