Phase II study in children and adults under 40 years with newly diagnosed Langerhans cell histiocytosis: protocol for an LCH-19-MSMFB clinical trial in Japan.

INTRODUCTION: Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series. METHODS AND ANALYSIS: This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over. ETHICS AND DISSEMINATION: This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians. TRIAL REGISTRATION NUMBER: jRCTs041210027.

[Evaluation of Pharmacy Students' Understanding of Clinical Trials and Research through Questionnaires Before and After the Hospital Practical Training].

A questionnaire survey was conducted to evaluate practical training and improve education on clinical trial and research. This survey was based on the results of questionnaire before and after the practical training undertaken by 240 pharmaceutical students (Kanto region; 1 university, Tokai region; 2 university, Kinki region; 9 university) at Mie University Hospital between 2011 and 2022. In the questionnaire before practical training, lectures in university (n=219, 91%) were the main source of information on clinical trials and research. Fifty-two students (22%) correctly answered the contents of phase 1-4 trials. As an occupation that can perform clinical research coordinator (CRC)'s work, only 7 students (3%) answered that "all medical and non-medical professionals" can perform the CRC's duties. Regarding the understanding of terms related to clinical trials and research, more than 90% of the students understood the meaning of "subjects," "informed consent," and "placebo" even before practical training. Otherwise, even after practical training, students' understanding of "reimbursement," "follow-up period," "audit," or "direct access" was less than 80%. Practical training improved the understanding of terms such as clinical trial (Wilcoxon signed-rank test, p<0.001), clinical research phase 1-4 trials (Wilcoxon signed-rank test, p<0.001), interest in clinical trials and research (McNemar-Bowker test, p<0.001), and understanding of CRC's work (McNemar-Bowker test, p<0.001). We will improve the content of practical training and bequeath the knowledge and importance of drug discovery and development to the next generation.

Flow cytometric profiles with CD7 and CADM1 in CD4+ T cells are promising indicators for prognosis of aggressive ATL.

ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a poor prognosis hematological malignancy originating from human T-cell leukemia virus 1 (HTLV-1)-infected CD4+ T cells. Flow cytometric plots of CADM1 and CD7 in CD4+ T cells are useful for separating HTLV-1-uninfected T cells and ATL cells. They are indicators of clonal evolution of HTLV-1-infected cells and disease progression of asymptomatic carriers or indolent ATL. However, the impacts of the plots on the clinical course or prognosis of ATL, especially in aggressive ATL, remain unclear. We focused on the N fraction (CD4+ CADM1+ CD7-) reflecting ATL cells and analyzed the flow cytometric profiles and clinical course of 497 samples from 92 HTLV-1-infected patients who were mainly aggressive ATL. The parameters based on N fractions showed significant correlations with known indicators of ATL disease status (soluble interleukin-2 receptor, lactate dehydrogenase, abnormal lymphocytes, etc.) and sensitively reflected the treatment response of aggressive ATL. The parameters based on N fractions significantly stratified the prognosis of aggressive ATL at 4 different time points: before treatment, after 1 course of chemotherapy, at the best response after chemotherapy, and before allogeneic hematopoietic cell transplantation. Even after mogamulizumab administration, which shows potent effects for peripheral blood lesions, the N fraction was still a useful indicator for prognostic estimation. In summary, this report shows that CADM1 vs CD7 plots in CD4+ T cells are useful indicators of the clinical course and prognosis of aggressive ATL. Therefore, this CADM1 and CD7 profile is suggested to be a useful prognostic indicator consistently from HTLV-1 carriers to aggressive ATL.

Sturge-Weber syndrome with cemento-ossifying fibroma in the maxilla and giant odontoma in the mandible: A case report.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with vascular lesions of the cerebral meninges, port wine spots on the face, and glaucoma of the eyes; it is a congenital, non-genetic disease whose etiology and mechanisms are unknown. In this report, we describe a rare case of SWS with unilateral large odontogenic tumors in the maxilla and mandible. The histopathological diagnosis of the maxillary bone lesion on biopsy was juvenile psammomatoid ossifying fibroma, which is considered a type of ossifying fibroma of craniofacial bone origin. However, the final pathological diagnosis of the excision was cemento-ossifying fibroma derived from periodontal ligament cells, and we discuss the histopathology in detail. In addition, the mandibular lesion was one of the largest odontomas reported to date. Furthermore, in this case, we suggest the possibility that the maxillary and mandibular bone lesions are not separate lesions, but a series of lesions related to SWS.