Osaka University Hospital (大阪大学医学部附属病院, Ōsaka daigaku igakubu fuzoku byōin) is a university hospital located in Suita, Osaka, Japan, affiliated with Osaka University.
Although novel drug development and clinical trials are ongoing, bisphosphonates remain the standard treatment of osteogenesis imperfecta (OI). This study aimed to evaluate clinical effects of bisphosphonate therapy across clinical subtypes and genetic variants of OI, and to explore treatment outcomes of sequential bisphosphonate therapy in patients with severe disease. This retrospective analysis was conducted using clinical data from patients with genetically confirmed OI. Bone mineral density (BMD), trabecular bone score (TBS), height, and fracture incidence were analyzed in patients undergoing pamidronate (PAM) treatment and in those who switched from PAM to zoledronate (ZOL). A total of 83 patients with OI were included, of whom 51 (type I: n = 36; type III: n = 9; type IV: n = 5; type V: n = 1) with a history of PAM treatment were selected for subgroup analysis. Analysis of up to 5 years of PAM treatment demonstrated a significant overall increase in BMD accompanied by a reduction in the annualized fracture rate. However, BMD improvement was significantly attenuated in patients with type III compared with those with other types (years 2–4, p < 0.001). Although BMD significantly increased in both groups following PAM initiation, the glycine-substitution group showed lower BMD than the haploinsufficiency group. Type III patients who switched from PAM to ZOL demonstrated increased BMD Z-scores and reduced fracture incidence. Switching from PAM to ZOL appears to be associated with improved outcomes in severe cases. These results suggest that clinical classification, alongside genotype information, may help inform prognosis and guide treatment strategies.
Robot-assisted minimally invasive esophagectomy (RAMIE) has become increasingly prevalent due to its ability to provide a magnified, three-dimensional operative field and articulate instrumentation. However, the narrow and fixed field of view creates peripheral blind zones. Assistant maneuvers and instrument movements frequently occur outside the console view, potentially affecting intraoperative situational awareness and workflow. These factors can lead to inadvertent injuries to adjacent organs such as the aorta, pulmonary vein, trachea, or lungs. This dynamic manuscript illustrates a practical visualization strategy using a 5-mm flexible sub-scope to address blind zones during robot-assisted esophagectomy. This manuscript presents synchronized intraoperative footage from the main robotic camera and a 5-mm flexible sub-scope used during the thoracic phase of RAMIE. Representative operative scenes were selected to demonstrate how the sub-scope provides complementary visualization of areas outside the console field of view. Quantitative assessment of visual coverage was performed in a representative case to illustrate the proportion of assistant activity occurring within and outside the robotic camera view. Additional illustrative scenarios highlight sub-scope utilization during port insertion, instrument exchange, vascular division, and assistant-led background tasks. Video analysis demonstrated that a substantial proportion of assistant forceps activity occurred outside the robotic camera’s field of view during the thoracic phase. The sub-scope enabled continuous visualization of these blind zones, allowing assistants to monitor instrument trajectories, surrounding structures, and spatial relationships without requiring repositioning of the main camera. Dynamic intraoperative examples illustrate how this complementary visualization supports safe confirmation during critical steps, facilitates autonomous assistant actions, and enables parallel task execution while preserving uninterrupted console workflow. This video-based report demonstrates a practical technique for dynamic visualization of peripheral blind zones during robot-assisted esophagectomy. A 5-mm flexible sub-scope may support intraoperative awareness and coordinated workflow while preserving the stability of the primary console view.
After a median study follow-up of 36.6 months, first-line pembrolizumab plus chemotherapy numerically improved overall survival (OS) and progression-free survival (PFS) versus placebo plus chemotherapy in Japanese participants with advanced esophageal cancer in the phase 3 KEYNOTE-590 study. The 5-year follow-up is presented. Participants with previously untreated advanced esophageal cancer were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks up to 35 cycles plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Primary end points were OS and PFS per RECIST v1.1 by investigator; objective response rate (ORR) and safety were secondary. The data cutoff date was July 10, 2023. In total, 141 of 794... participants were enrolled in Japan. Median study follow-up was 60.6 months (range, 53.8–69.7). Median OS was 17.7 months (95
BACKGROUND:Ifinatamab deruxtecan is a novel B7-H3-directed antibody-drug conjugate that leverages the clinically validated deruxtecan technology. We report dose-escalation results from a trial of ifinatamab deruxtecan in patients with solid tumours. METHODS:In this two-part, multicentre, open-label, first-in-human, phase 1/2 study of ifinatamab deruxtecan conducted at clinics in ten hospitals and cancer centres in the USA and Japan, we recruited patients aged 18 years or older who had advanced treatment-refractory solid tumours (small-cell lung cancer, oesophageal squamous cell carcinoma, castration-resistant prostate cancer, squamous non-small-cell lung cancer, head and neck squamous cell carcinoma, bladder cancer, sarcoma, endometrial cancer, melanoma, or breast cancer), and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received ifinatamab deruxtecan at doses of 0·8-16·0 mg/kg intravenously every 3 weeks. The primary outcome of dose escalation was the safety profile, which was evaluated in patients who received one or more dose of ifinatamab deruxtecan. Antitumour activity (per Response Evaluation Criteria in Solid Tumours version 1.1; secondary outcome) was evaluated in patients receiving ifinatamab deruxtecan at doses of 4·8 mg/kg or higher. The data cutoff was Jan 31, 2023. This trial is registered with ClinicalTrials.gov (NCT04145622) and is ongoing. FINDINGS:Between Oct 25, 2019, and July 13, 2022, 97 patients were enrolled and treated. 77 (79%) patients were male and 20 (21%) were female, 56 (58%) patients were White, and 31 (32%) were Asian. Three patients (3%) had dose-limiting toxicities; however, on the basis of protocol-defined criteria, the maximum tolerated dose was not reached. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were anaemia (17 [18%] patients), neutropenia (four [4%]), lymphocyte count decreased (three [3%]), and neutrophil count decreased (three [3%]). Serious TEAEs occurred in 31 (32%) patients. TEAEs associated with death were reported in five patients (5%; pneumonia, pneumonia aspiration, COVID-19 pneumonia, interstitial lung disease, and one death of undesignated cause); death due to interstitial lung disease was considered related to study medication by the investigator. After a median follow-up of 8·6 months (IQR 4·1-12·9), the confirmed objective response rate across tumour types was 34% (95% CI 23-47; 24 of 70 evaluable patients). INTERPRETATION:The maximum tolerated dose was not reached with ifinatamab deruxtecan; however, one death due to treatment-related interstitial lung disease highlights the importance of prompt evaluation and careful management of patients who develop interstitial lung disease. Promising antitumour activity was observed across various solid tumours. These findings support further evaluation of ifinatamab deruxtecan in randomised controlled trials. FUNDING:Funding for this study was provided by Daiichi Sankyo Company (Daiichi Sankyo) and Merck Sharp & Dohme, a subsidiary of Merck, Rahway, NJ, USA.
The purpose of this narrative review is to provide a clinic-ready synthesis of contemporary concepts in peripheral neuropathy, spanning epidemiology, diagnosis, and treatment, with emphasis on high-yield advances applicable to daily practice. The authors integrate pragmatic tools-including a diagnostic algorithm, suggested initial laboratory panels, and commonly used outcome measures-to support clinical decision-making. However, this review is intended as a clinic-oriented synthesis rather than a formal practice guideline. Peripheral neuropathy can be systematically categorized into seven pathophysiologic phenotypes-(1) distal "dying-back" axonopathy, (2) neuronopathy (ganglionopathy), (3) demyelinating neuropathies, (4) small-fiber neuropathy, (5) autonomic neuropathy, (6) ischemic/infiltrative/inflammatory axonopathies, and (7) focal compressive/entrapment neuropathies. An organized evaluation and management around this phenotype-first structure, combined with a structured stepwise escalation algorithm (from bedside pattern recognition to targeted laboratory testing, electrodiagnostics, selective imaging, small-fiber assessment, and immune work-up when indicated), bridges fragmented evidence into a clinic-ready decision-support framework that improves diagnostic precision, rational test utilization, and therapeutic alignment. Beyond optimizing pharmacologic care, neuromodulation may expand options in carefully selected patients. For painful diabetic peripheral neuropathy (DPN), high‑frequency (10 kHz) spinal cord stimulation (SCS) has been evaluated in randomized comparative studies against optimized medical management and has been associated with sustained pain reduction and functional improvement through 24 months in follow‑up reports, supporting consideration in medication‑refractory cases where access and patient factors permit. Ultrasound ‑guided pulsed radiofrequency (PRF)-a nondestructive, field‑based neuromodulation that limits tip temperature to <42 °C-has been studied in small randomized trials and observational cohorts for focal entrapment‑type neuropathic pain after positive diagnostic blocks; reported benefits are generally short‑ to mid‑term with heterogeneous protocols, so certainty varies by indication. For hereditary transthyretin amyloid polyneuropathy (ATTRv), disease‑modifying approaches-including nucleic acid-based therapies-are increasingly integrated into contemporary care. Overall, these developments support earlier pattern recognition, more precise phenotyping, and rational escalation while using standardized outcome measures to track response.
