RESUMO
As the coronavirus disease 2019 (COVID-19) pandemic rages on, it is important to explore new evolution-resistant vaccine antigens and new vaccine platforms that can produce readily scalable, inexpensive vaccines with easier storage and transport. We report here a synthetic biology-based vaccine platform that employs an expression vector with an inducible gram-negative autotransporter to express vaccine antigens on the surface of genome-reduced bacteria to enhance interaction of vaccine antigen with the immune system. As a proof-of-principle, we utilized genome-reduced Escherichia coli to express SARS-CoV-2 and porcine epidemic diarrhea virus (PEDV) fusion peptide (FP) on the cell surface, and evaluated their use as killed whole-cell vaccines. The FP sequence is highly conserved across coronaviruses; the six FP core amino acid residues, along with the four adjacent residues upstream and the three residues downstream from the core, are identical between SARS-CoV-2 and PEDV. We tested the efficacy of PEDV FP and SARS-CoV-2 FP vaccines in a PEDV challenge pig model. We demonstrated that both vaccines induced potent anamnestic responses upon virus challenge, potentiated interferon-γ responses, reduced viral RNA loads in jejunum tissue, and provided significant protection against clinical disease. However, neither vaccines elicited sterilizing immunity. Since SARS-CoV-2 FP and PEDV FP vaccines provided similar clinical protection, the coronavirus FP could be a target for a broadly protective vaccine using any platform. Importantly, the genome-reduced bacterial surface-expressed vaccine platform, when using a vaccine-appropriate bacterial vector, has potential utility as an inexpensive, readily manufactured, and rapid vaccine platform for other pathogens.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Vírus da Diarreia Epidêmica Suína/imunologia , SARS-CoV-2/imunologia , Proteínas Virais de Fusão/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Escherichia coli/genética , Genoma Bacteriano , Interferon gama/sangue , RNA Viral/análise , Suínos , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/imunologiaRESUMO
Mucormycosis is a frequently lethal fungal infection that most commonly affects patients with poorly controlled diabetes or other immunosuppressed states. We report the case of a suspected disseminated Rhizopus infection in a patient who was pursuing naturopathic treatment including mud baths for metastatic adrenocortical carcinoma. He was empirically treated with liposomal amphotericin B but opted to stop treatment following multiorgan failure. The patient passed away on the tenth day of his hospital admission.
RESUMO
Targeted therapies, including BRAF and MEK inhibitors, are valuable treatment options for patients with unresectable or metastatic BRAF V600-mutant melanoma. With the improvement in survival seen with modern melanoma therapeutics, clinicians are learning the variable patterns associated with extended clinical courses. Sarcoidosis is characterized by non-caseating granulomatous inflammation of unknown etiology, often presenting with cutaneous, lung, or lymph node involvement. There is a known association between sarcoidosis and melanoma, and sarcoidosis is increasingly seen and described in the setting of anti-melanoma therapy. The challenge for clinicians is to differentiate between sarcoid-related and malignancy-related findings, which may follow a variable course over years. We present two cases of BRAF and MEK inhibitor-related sarcoidosis in patients with melanoma and review the literature. The dynamic nature of the clinical and radiographic findings impacted patient management and clinical decisions for years of their treatment course.
RESUMO
Background and Objective: Primary and metastatic liver tumors are a significant cause of mortality worldwide. Regardless of the etiology of the tumor, macro- and microscopically clear margins (R0) while preserving adequate function of the remaining organ are the main goals after liver resections. However, technically challenging procedures are required to achieve R0 resection. Currently, there is no consensus of which should be the ideal minimal safety margin for liver tumor resections, with contrasting reports in regards of safety, tumor recurrence and overall outcomes following R0. Therefore, we aim to review current worldwide surgical practices to achieve R0 resections for primary and metastatic liver tumors in challenging surgical techniques and their reported outcomes. Methods: PubMed database, Google Scholar, and OVID Medline were searched for peer-reviewed original articles related to surgical techniques performed to achieve R0 resections in the setting of primary and/or metastatic liver tumors. An up-to-date review of English-language articles published between 2015 to July 2022 was performed. Key Content and Findings: Primary and metastatic liver tumors can be effectively treated using hepatic resection. Current literature highlights that tumors involving major vascular structures are not uncommon. Surgical advances have allowed for vascular control techniques, as well as vascular resections to be performed in a feasible and safe manner to achieve R0 resections. Complex resections combining surgical techniques can be performed in certain population after a detailed evaluation. Liver transplantation (LT) have been used with varying degrees of success for treatment of patients with hepatocellular carcinoma, cholangiocarcinoma (CCA), colorectal liver metastases (CRLM), non-resectable CRLM and metastatic neuroendocrine tumors. Conclusions: Safety and feasibility of R0 resections have been reported for multiple techniques. Technical complexity should not be a limitation to achieve or pursue R0 tumor resection. However, there has to be a balance between patient risk/benefit in attempting R0 resections. Adequate training of surgeons on implementation of complex techniques, as well as transplant oncology techniques applied to hepato-pancreato-biliary (HPB) surgery represents as a promising path to improve short and long-term outcomes for liver-related oncology patients.
RESUMO
OBJECTIVE: The role of stereotactic radiosurgery (SRS) in the management of recurrent and residual intracranial primary melanocytomas (PMC) remains unclear. The aim of this study is to evaluate the safety and efficacy of SRS in the management of these rare tumors. METHODS: One patient treated with SRS in our institution for an intracranial PMC was retrospectively identified. Additionally, a systematic review of English articles using MEDLINE was performed to identify studies reporting on treatment and tumor characteristics and patient outcomes following SRS-management of intracranial PMC. RESULTS: Including our institution's patient, a total of 13 patients (11 male and 2 female) met the inclusion criteria and were analyzed. The median age at SRS treatment was 49 years (interquartile range [IQR] 27). At a median follow-up of 24 (IQR 48) months, the aggregate local tumor-control rate was 76.9%. Progression occurred in 3 patients and was managed with repeat SRS (1 of 13) or salvage resection (2 of 13). One case of malignant transformation to melanoma leading to leptomeningeal dissemination and death was noted. CONCLUSIONS: SRS appears to be a reasonable treatment option for recurrent and residual melanocytomas. A higher prescription dose might be reasonable in the treatment of intermediate grade or recurring PMC. Close longitudinal follow-up for recurrence or malignant transformation of melanocytomas after SRS is recommended.