University of Tokyo Hospital

Lay Summary Efficacy of ustekinumab for hospitalized patients with severe ulcerative colitis (UC) was investigated in this study. Ustekinumab may be an effective treatment option for acute severe UC because of efficacy and rapid therapeutic onset.

In recent years, plasma levels of phosphorylated tau species, particularly p-tau217, have emerged as reliable indicators of amyloid-β (Aβ) pathology in the brain. However, real-world data on plasma biomarkers across diverse populations remain limited. We conducted a prospective multicenter study under real-world clinical settings to evaluate diagnostic performance of plasma biomarkers, including p-tau217, in discriminating amyloid status among a Japanese population. A total of 332 participants were recruited from seven memory clinics across Japan. Participants were categorized into four clinical subgroups: cognitively unimpaired (CU), mild cognitive impairment (MCI), Alzheimer’s disease dementia (ADD), and non-ADD. We measured Aβ40, Aβ42, p-tau181, total-tau, and neurofilament light chain (NfL) in CSF and Aβ40, Aβ42, p-tau217, p-tau181, glial fibrillary acidic protein (GFAP) and NfL in plasma using the LUMIPULSE platform. Amyloid status was determined by amyloid PET imaging and/or CSF Aβ42/40 ratio. Significant differences were observed in plasma biomarker levels, including Aβ42/40, p-tau217, p-tau181, GFAP, and NfL across clinical categories. Plasma p-tau217 and p-tau217/Aβ42 achieved high diagnostic accuracy, with areas under the curve (AUC) exceeding 0.9 with PET amyloid status as the reference, demonstrating comparable performance to the in vitro diagnostic (IVD)-approved CSF Aβ42/40 ratio. The two-cutoff approach using plasma p-tau217 and p-tau217/Aβ42 to achieve 90% sensitivity and 90% specificity provided high negative and positive predictive values. The intermediate range defined by these two-cutoff points was narrower for p-tau217/Aβ42 than for p-tau217. The predefined U.S. Food and Drug Administration (FDA)-approved two-cutoff points were applicable to this cohort with good accuracy. Concordance of plasma p-tau217 or p-tau217/Aβ42 with PET or CSF Aβ42/40 status ranged from 87% to 93%, although larger discordant results were observed in the non-ADD group. This study demonstrates the clinical utility of plasma p-tau217 and p-tau217/Aβ42 ratio for real-world diagnostic evaluations of dementia. However, careful interpretation of plasma biomarker is warranted in cases showing discordant results with PET or CSF findings.

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) affects over 600,000 individuals worldwide each year, and its incidence continues to rise. There is a growing need for novel therapeutic strategies that achieve high antitumor efficacy while minimizing functional impairment. We developed a novel approach to enhance intracellular delivery of immunotoxins (ITs) by combining a photosensitizer under illumination. This method, termed intelligent Targeted Anti-body Phototherapy (iTAP), utilizes light as a spatiotemporal trigger to promote the cytoplasmic release of toxins. In the present study, we investigated the in vivo therapeutic efficacy of iTAP using an EGFR-targeted IT composed of cetuximab conjugated to saporin (IT-Cmab), administered in combination with the clinically used photodynamic therapy (PDT) photosensitizer NPe6, in a xenograft mouse model. Methods: Sa3 cells were implanted subcutaneously into the right hind limb of nude mice. Mice were randomized into four groups (n = 5): (i) iTAP (IT-Cmab plus NPe6), (ii) IT-Cmab alone, (iii) NPe6 alone, and (iv) saline control. Treatment was initiated once tumors exceeded 40 mm3. Mice received intraperitoneal IT-Cmab (0.5 mg/kg), followed 72 h later by intravenous NPe6 (5 mg/kg). Tumors were irradiated 3-4 h later using a custom LED device (670 nm, 262 mW/cm2, 30 J/cm2). Tumor volume and body weight were monitored over time, and antitumor effects were analyzed using a linear mixed-effects model. Results: iTAP treatment produced the earliest and most pronounced inhibition of tumor growth among the four groups. Significant suppression was observed from day 9 and persisted throughout the study. IT-Cmab alone showed a moderate but sustained antitumor effect with a later onset, whereas NPe6-mediated PDT exhibited only a delayed and weaker response. On the final day, median tumor volumes showed substantial reductions relative to the Control group (601%), with decreases of 41% in PDT (357%), 55% in IT-Cmab (271%), and 70% in iTAP (178%). Overall, iTAP demonstrated the strongest and most durable therapeutic efficacy in vivo. Conclusions: These findings indicate that iTAP represents a promising therapeutic strategy for HNSCC.