The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.
Boerhaave's syndrome is a rare but potentially fatal condition characterised by a transmural tear of the distal oesophagus induced by a sudden increase in pressure. Diagnosis is challenging as the classic triad of vomiting, abdominal or chest pain, and subcutaneous emphysema is absent in many patients. Management is multidisciplinary and relies on rapid, distinct, and repeated imaging. Treatment has not been standardised and may be conservative, endoscopic, or surgical. We present a typical case which illustrates possible diagnostic pitfalls and the therapeutic conundrum surrounding management of the syndrome. Based on time of presentation and eventual presence of sepsis, a therapeutic algorithm is proposed.
ObjectivesTo assess image quality in abdominal CT at low tube voltage combined with two types of iterative reconstruction (IR) at four reduced contrast agent dose levels.MethodsMinipigs were scanned with standard 320 mg I/mL contrast concentration at 120 kVp, and with reduced formulations of 120, 170, 220 and 270 mg I/mL at 80 kVp with IR. Image quality was assessed by CT value, dose normalized contrast and signal to noise ratio (CNRD and SNRD) in the arterial and venous phases. Qualitative analysis was included by expert reading.ResultsProtocols with 170 mg I/mL or higher showed equal or superior CT values: aorta (278–468 HU versus 314 HU); portal vein (205–273 HU versus 208 HU); liver parenchyma (122–146 HU versus 115 HU). In the aorta, all 170 mg I/mL protocols or higher yielded equal or superior CNRD (15.0–28.0 versus 13.7). In liver parenchyma, all study protocols resulted in higher SNRDs. Radiation dose could be reduced from standard CTDIvol = 7.8 mGy (6.2 mSv) to 7.6 mGy (5.2 mSv) with 170 mg I/mL.ConclusionCombining 80 kVp with IR allows at least a 47 % contrast agent dose reduction and 16 % radiation dose reduction for images of comparable quality.Key Points• There is a balance between image quality, contrast dose and radiation dose.• Iterative reconstruction has a major, positive impact on this balance.• Both contrast dose and radiation dose can be reduced in abdominal CT.• The trade-off can be quantitatively described by a 3D model.• Contrast and radiation dose can be tailored according to specific safety concerns.
Necrotizing fasciitis is a rapidly progressive soft tissue infection that involves subcutaneous fat and spreads along the fascial planes. This disease has a potentially fatal outcome if not recognized in early. Several cases have been reported of a possible association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the development or aggravation of necrotizing fasciitis. This association is still a subject of controversy. In this article we present a case of fatal necrotizing fasciitis occurring in association with intramuscular injections of diclofenac in a patient who was admitted for the symptoms of a urinary stone. Our opinion is that the intramuscular injections caused a locally aseptic necrosis, which was secondarily invaded by. Since this incident, our policy is to avoid the use of intramuscular injections of diclofenac and other NSAIDs in cases of potentially infectious diseases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.