8 research outputs found
Helicobacter cinaedi-associated Carotid Arteritis
A 65-year-old Japanese man with bilateral carotid atherosclerosis presented with right neck pain and fever. Contrast-enhanced computed tomography suggested carotid arteritis, and carotid ultrasonography showed an unstable plaque. The patient developed a cerebral embolism, causing a transient ischemic attack. Helicobacter cinaedi was detected in blood culture, and H. cinaedi-associated carotid arteritis was diagnosed. Empirical antibiotic therapy was administered for 6 weeks. After readmission for recurrent fever, he was treated another 8 weeks. Although the relationship between H. cinaedi infection and atherosclerosis development remains unclear, the atherosclerotic changes in our patientās carotid artery might have been attributable to H. cinaedi infection
Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor
Background: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. Purpose: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. Patients and methods: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. Results: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32ā86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). Conclusions: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy
Three distinct mechanisms underlying human Ī³Ī“ T cell-mediated cytotoxicity against malignant pleural mesothelioma
IntroductionMalignant pleural mesothelioma (MPM) is a rare and highly aggressive thoracic tumor with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors exhibit a promising effect in some patients with unresectable MPM in clinical trials, the majority of MPM patients show only modest response rates to the currently available treatments. It is thus imperative to develop novel and innovative therapeutic modalities for MPM, including immune effector cell-based therapies.MethodsĪ³Ī“ T cells were expanded using tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2, and the therapeutic potential of Ī³Ī“ T cells was examined through analyzing cell surface markers and cellular cytotoxicity against MPM in vitro using a europium chelate-based time-resolved fluorescence assay system and a luciferase-based luminescence assay system.Results and discussionWe successfully expanded Ī³Ī“ T cells from peripheral blood mononuclear cells of healthy donors and MPM patients. Ī³Ī“ T cells expressed natural killer receptors such as NKG2D and DNAM-1 and exhibited a moderate level of cytotoxicity to MPM cells in the absence of antigens. The inclusion of PTA, (E)-4-hydroxy-3- methylbut-2-enyl diphosphate (HMBPP) or zoledronic acid (ZOL) induced a TCR-dependent cytotoxicity in Ī³Ī“ T cells and secreted interferon-Ī³ (IFN-Ī³). In addition, Ī³Ī“ T cells expressing CD16 exhibited a significant level of cytotoxicity against MPM cells in the presence of an anti-epidermal growth factor receptor (EGFR) mAb, at lower concentrations than in clinical settings, whereas a detectable level of IFN-Ī³ was not produced. Taken together, Ī³Ī“ T cells showed cytotoxic activity against MPM in three distinct mechanisms through NK receptors, TCRs and CD16. Since major histocompatibility complex (MHC) molecules are not involved in the recognition, both autologous and allogeneic Ī³Ī“ T cells could be used for the development of Ī³Ī“ T cell-based adoptive immunotherapy for MPM
Phase I Study to Assess the Safety and Immunogenicity of an Intradermal COVID-19 DNA Vaccine Administered Using a Pyro-Drive Jet Injector in Healthy Adults
We conducted a nonrandomized, open-label phase I study to assess the safety and immunogenicity of an intradermal coronavirus disease 2019 (COVID-19) DNA vaccine (AG0302-COVID-19) administered using a pyro-drive jet injector at Osaka University Hospital between Yanagida November 2020 and December 2021. Twenty healthy volunteers, male or female, were enrolled in the low-dose (0.2 mg) or high-dose (0.4 mg) groups and administered AG0302-COVID19 twice at a 2-week interval. There were no adverse events that led to discontinuation of the study drug vaccination schedule. A serious adverse event (disc protrusion) was reported in one patient in the high-dose group, but the individual recovered, and the adverse event was not causally related to the study drug. In the analysis of the humoral immune response, the geometric mean titer (GMT) of serum anti-SARS-CoV-2 spike glycoprotein-specific antibody was low in both the low-dose and high-dose groups (246.2 (95% CI 176.2 to 344.1, 348.2 (95% CI 181.3 to 668.9)) at the 8 weeks after first vaccination. Regarding the analysis of the cellular immune, the number of IFN-γ-producing cells responsive to the SARS-CoV-2 spike glycoprotein increased with individual differences after the first dose and was sustained for several months. Overall, no notable safety issues were observed with the intradermal inoculations of AG0302-COVID19. Regarding immunogenicity, a cellular immune response was observed in some subjects after AG0302-COVID19 intradermal inoculation, but no significant antibody production was observed
Phase II study of IRInotecan treatment after COmbined chemoāimmunotherapy for extensiveāstage small cell lung cancer: Protocol of IRICO study
Abstract Introduction Combined treatment using antiāprogrammed deathāligand 1 antibody (antiāPDāL1) and platinumāetoposide is the current standard firstāline treatment for patients with extensiveāstage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ESāSCLC after the firstāline treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ESāSCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the secondā or laterāline setting for patients with ESāSCLC who have been previously treated with combined treatment. Methods Our study will enroll total 30 patients who are diagnosed with ESāSCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4āweeks. Doses of irinotecan (100/80/60āmg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progressionāfree survival, and safety. Discussion Since the present firstāline treatment has been changed to the combined treatment, the secondā or laterāline treatment should be reāevaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and reāevaluates the clinical benefits of irinotecan after combined treatment with antiāPDāL1 and platinumāetoposide for patients with ESāSCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021