Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

Background/Aims@#The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. @*Methods@#SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. @*Results@#Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). @*Conclusions@#These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Segmental Arteries and Veins at Higher Lumbar Levels Can Intersect the Adjacent Caudal Intervertebral Disc in the Anterior Part of the Spinal Column: A Cadaveric Analysis

Methods@#Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column. @*Results@#The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively. @*Conclusions@#The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.

New Insights in Resistant Diabetic Macular Edema.

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic eyes, and due to the rapid rise in the number of diabetic patients, the treatment burden has increased exponentially. The introduction of antivascular endothelial growth factor (anti-VEGF) therapy has been a major breakthrough in the management of center-involving DME, replacing laser photocoagulation as the first-line treatment. Despite the improvement in DME treatment with anti-VEGF therapy, persistent DME remains a challenge due to the extremely complex pathogenesis and the involvement of several different biochemical pathways. This review focuses on therapeutic options for persistent DME, which include corticosteroids, laser, and surgery. Novel agents for DME control such as new anti-VEGF, interleukin inhibitor, Rho-kinase inhibitor, and neuroprotective agents that are being investigated are reviewed as well. Future treatment perspectives include an individualized DME management.

p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells Stimulated by Tumor Necrosis Factor-α

Methods@#HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. @*Results@#TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. @*Conclusions@#This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

Bartonella hanselae retinitis patient evaluated with multimodal retinal exams.

BACKGROUND: Cat scratch disease is a systemic infectious illness caused by the bacterium Bartonella henselae. The most common ophthalmological involvement due to infection by Bartonella is Parinaud oculoglandular syndrome, whereas the most common posterior segment findings are neuroretinitis and subsequent late macular star. Moreover, other findings, such as retinal or subretinal lesions, intermediate uveitis and angiomatous lesions, may be present. CASE PRESENTATION: A 37-year-old female patient with retinal findings and serological confirmation of Bartonella infection was evaluated via multimodal retinal exams. The patient received treatment with doxycycline 100 mg twice daily for 2 weeks. One month after treatment, complete improvement of her visual scotoma symptoms was confirmed. A swept-source optical coherence tomography exam also showed decreases in the size and intraretinal extension of the lesion. Improvement of light perception at the affected area was confirmed by microperimetry. CONCLUSIONS: Bartonella henselae infection, particularly retinitis, can present a variable spectrum of clinical and ophthalmological findings. Multimodal retinal exams can clearly identify lesion characteristics, thus providing important information for diagnosis and the evaluation of lesion improvement after antibiotic treatment.

Fog simulation using a mesoscale model in and around the Yodo River Basin, Japan.

In this study, fog simulations were conducted using the Fifth-Generation NCAR/Penn State Mesoscale Model (MM5) in and around the Yodo River Basin, Japan. The purpose is to investigate the MM5 performance of fog simulation for long-term periods. The simulations were performed for January, February, March, and July, 2005 with a coarse 3-km and a nested fine 1-km grid domains. Results of the simulations were compared with data from ten meteorological observatories, fog sampling site in Mt. Rokko, and visibility measurement sites along the Second Meishin Expressway. At the meteorological observatories, the MM5 predictions agreed well with the observed temperature and specific humidity. In the Mt. Rokko region, MM5 generally reproduced the occurrence of relatively thick fog events but tended to overestimate liquid water content (LWC) of fog (by factors of 2.2-3.3 in terms of monthly mean LWC). In the Second Meishin Expressway region, while MM5 identified the specific sites at which fog either frequently or seldom occurs, the model underestimated the monthly fog frequencies by factors of more than 1.5. Overall, MM5 reproduced the general trend of fog events, and the model performance may be improved by using more adequate land surface data and suitable physics options for our study.