Diffuse glioma growth: a guerilla war

In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS–28–erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation

Real-world comparative effectiveness study of Janus kinase inhibitors compared to biologic disease-modifying antirheumatic drugs in Korean patients with rheumatoid arthritis

OBJECTIVES: To evaluate the real-world effectiveness and safety of Janus kinase inhibitors (JAKis) compared to biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with rheumatoid arthritis (RA) who have not previously been treated with either JAKis or bDMARDs. METHODS: This prospective, multicenter, observational study was conducted at 17 centres in the Republic of Korea. Patients with an inadequate response to methotrexate were enrolled and started treatment with either JAKis or bDMARDs. The primary endpoint was the proportion of patients achieving low disease activity (LDA) at 24 weeks, measured by the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR). Secondary endpoints included the remission rate at 24 weeks, and LDA and remission rates at 48 weeks. Safety was assessed by the exposure-adjusted event rate (EAER) of adverse events (AEs), adjusted for length of the follow-up period and presented per 100 person-years. RESULTS: A total of 506 patients were enrolled, with 253 patients in each group. Among bDMARD users, 60.1 % received tumour necrosis factor inhibitors (TNFis; n = 152) and 39.9 % received non-TNFis (n = 101). At 24 weeks, 48.2 % of the JAKi group achieved LDA, as did 42.7 % of the bDMARD group. Remission rates at 24 weeks were 28.9 % for the JAKi group and 27.3 % for the bDMARD group. At 48 weeks, there were no significant intergroup differences in the EAER of overall AEs. CONCLUSIONS: In this observational real-world study of Korean patients with RA who were eligible for targeted therapy, JAKis demonstrated comparable effectiveness and safety to bDMARDs

Elevated interleukin-25 and its association to Th2 cytokines in systemic lupus erythematosus with lupus nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is associated with lupus nephritis, initiated by the deposition of immune complexes in the kidney; subsequently, this induces the overexpression of cytokines. Lupus nephritis is known as one of the major clinical manifestations that affect the disease severity in SLE patients. An increased number of resident periglomerular and immune cells in the kidney has the potential to affect the equilibrium of different immune cell subsets, such as Th1, Th2, Th17, and Tregs, which may be central to the induction of tissue damage in kidney by exerting either proinflammatory or anti-inflammatory effects, or both. This equilibrium has yet to be confirmed, as new players such as IL-25 remain undiscovered. IL-25 is a cytokine of the IL-17 family, which stimulates Th2-mediated immune response when overly expressed. Thus, the aim of this research is to determine the plasma levels of IL-25 and Th2-associated cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) in SLE patients with (SLE-LN) and without lupus nephritis. Sixty-four (n = 64) SLE patients and fifteen (n = 15) healthy individuals were recruited. This study demonstrated that the IL-9, IL-10 and IL-25 had significantly increased expressions in SLE-LN, followed by SLE without LN, compared to healthy controls. Meanwhile, IL-5 and IL-6 had significantly reduced. No significant difference was observed with IL-13, while the level of IL-4 was undetectable. Furthermore, IL-9 and IL-10 were significantly correlated with the IL-25, and IL-25, IL-9 and IL-10 were positively correlated with the disease severity score, SLEDAI. In conclusion, IL-25 and its associated Th2 cytokines (IL-9 and IL-10) may be involved in SLE pathogenesis. These cytokines could be potential biomarkers in monitoring and predicting the disease severity during SLE pathogenesis