作者: Takahashi, Ken ; Seno, Hiroshi ; Yaku, Hiroaki ; Shiokawa, Masahiro ; Uza, Norimitsu ; Okada, Hirokazu ; Kodama, Yuzo ; Kobiyama, Kouji ; Ishii, Ken J

Pancreatic cancer is one of the most refractory malignancies. In situ vaccines (ISV), in which intratumorally injected immunostimulatory adjuvants activate innate immunity at the tumor site, utilize tumor-derived patient-specific antigens, thereby allowing for the development of vaccines in patients themselves. Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy that selectively kills cancer cells exclusively in the NIR-irradiated region. Extending our previous research showing that ISV using the unique nanoparticulate Toll-like receptor 9 (TLR9) ligand K3-SPG induced effective antitumor immunity, here we incorporated NIR-PIT into K3-SPG-ISV so that local tumor destruction by NIR-PIT augments the antitumor effect of ISV. In the mouse model of pancreatic cancer, the combination of K3-SPG-ISV and CD44-targeting NIR-PIT showed synergistic systemic antitumor effects and enhanced anti-programmed cell death-1 (PD-1) blockade. Mechanistically, strong intratumoral upregulation of interferon-related genes and dependency on CD8⁺ T cells were observed, suggesting the possible role of interferon and cytotoxic T cell responses in the induction of antitumor immunity. Importantly, this combination induced immunological memory in therapeutic and neoadjuvant settings. This study represents the first attempt to integrate NIR-PIT with ISV, offering a promising new direction for cancer immunotherapy, particularly for pancreatic cancer.

2024-11-01·Journal of Vascular Surgery: Venous and Lymphatic Disorders

Clinical outcomes after treatment of incompetent saphenous vein combined with segmental popliteal vein reflux

Article

作者: Hong, Ki Pyo

OBJECTIVEThis study aimed to evaluate whether differences exist in the quality of life changes and complication rates after treatment of incompetent saphenous vein (ISV) based on the presence of segmental popliteal vein reflux (SPVR).METHODSPatients who underwent treatment for ISV from July 2016 to July 2021 were included and divided into two groups: patients without deep venous reflux (DVR) and patients with SPVR. Patients with axial DVR, a history of deep vein thrombosis, a history of orthopedic surgery, previous venous treatment, and no postoperative follow-up were excluded from the study. Duplex ultrasound examination was performed preoperatively and at 6 and 12 months postoperatively.RESULTSThe study included 233 patients (398 limbs), and 50 (64 limbs) had SPVR. Differences were not observed in gender, age, body mass index, distribution of clinical class according to Clinical-Etiology-Anatomy-Physiology classification, laterality, treatment method, and preoperative Venous Clinical Severity Score or Aberdeen Varicose Vein Questionnaire scores between the two groups with SPVR or without DVR. Furthermore, the Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire scores at 6 and 12 months postoperatively were improved in both groups, although without significant differences. A significant difference was not observed in the rate of postoperative complications between the groups based on the presence of SPVR (1.8% vs 1.6%: P = .896). The SPVR improvement rate after ISV treatment was 25% (16/64), and patient-reported outcomes in patients combined with SPVR improved independent of treatment modality, saphenous vein treatment section, and postoperative SPVR improvement.CONCLUSIONSComplication rates and clinical outcomes after ISV treatment did not differ in the presence of SPVR. In patients with SPVR, after ISV treatment, quality of life improved regardless of treatment modality, saphenous vein treatment section, and postoperative SPVR improvement.

2024-10-01·Transplantation and Cellular Therapy

Real-World Experience with Isavuconazole in Allogeneic Stem Cell Transplantation in Spain

Article

作者: Suarez-Lledó, Maria ; Solano, Carlos ; Vallejo, Juan Carlos ; Torrent, Anna ; Bautista, Guiomar ; Bailen, Rebeca ; Oarbeascoa, Gillen ; Gonzalez, Soledad ; Heras, Inmaculada ; Torres, Melissa ; Izquierdo, Isabel ; Espigado, Ildefonso ; Cadenas, Irene Garcia ; Vazquez, Lourdes ; Yañez, Lucrecia ; Lopez-Jiménez, Javier ; Chinea, Anabelle ; Martinez, Ariadna Perez ; Roldan, Elisa ; Casas, Maria Angeles Cuesta ; Calbacho, Maria ; Sierra, Pedro Gonzalez ; Cascón, Maria Jesus Pascual ; Kwon, Mi ; Parody, Rocio ; Gómez-Centurión, Ignacio ; Borrero, Asunción

Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis. We analyzed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC). We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC). A total of 166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacologic interactions. Twenty-one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, which led to ISV withdrawal in 7 patients (4%). ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.

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