RESUMEN
The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
RESUMEN
Backgrounds: The clinical and socioeconomic effects of COVID-19 are still being felt through-out the world. The disease affects people of all age groups, but it is known to have a milder clinical course in children including neonates. There is paucity of data from Sub-Saharan Africa on neonatal COVID-19 infection, and no such case has been reported in the literature in Ghana. Case presentation: This study presented a case report of a neonate who was found to be positive for COVID-19 infection after presenting symptoms such as respiratory distress, rhinorrhoea, and cough. This neonate was managed with in-hospital standard protocol for sepsis with a focus on pneumonia. Conclusion(s): The national guidelines on COVID-19 management were used for the neonate who was recovered and discharged.Copyright © 2021, TMU Press.
RESUMEN
The objective of this research was to understand the current situation and challenges associated with the internationalization of the curriculum (IoC) in English-medium instruction (EMI) programs at Japanese universities in the context of the COVID-19 pandemic. Utilizing a conceptual framework and ideas of ‘enablers’ and ‘blockers’ of IoC, we analyzed the qualitative data from interviews with 11 faculty members involved in both in-class and online teaching in EMI programs at different Japanese universities. Findings from our analysis revealed a general lack of awareness of IoC, with those that were aware either relating it to the international nature of their academic disciplines or expressing uncertainty in how to incorporate IoC into pedagogical practices. Perceived blockers included quantitative approaches to internationalization policy and funding at the government-level that largely neglected IoC, a lack of commitment and organizational support at the institutional level, and constraints on physical international mobility due to the pandemic. Enablers included the expansion of collaborative online international learning (COIL) programs for virtual student mobility and the general commitment to academic freedom in Japan that allows educators to teach without excessive external interference, enabling them to personally internationalize their curriculum if they wished to do so. The findings suggest that IoC is still a novel concept in Japan that may evolve in the dramatically altered higher education landscape going forward. © 2022, Hiroshima University,Research Institute for Higher Education,. All rights reserved.
RESUMEN
Backgrounds: The clinical and socioeconomic effects of COVID-19 are still being felt through-out the world. The disease affects people of all age groups, but it is known to have a milder clinical course in children including neonates. There is paucity of data from Sub-Saharan Africa on neonatal COVID-19 infection, and no such case has been reported in the literature in Ghana. Case presentation: This study presented a case report of a neonate who was found to be positive for COVID-19 infection after presenting symptoms such as respiratory distress, rhinorrhoea, and cough. This neonate was managed with in-hospital standard protocol for sepsis with a focus on pneumonia. Conclusion: The national guidelines on COVID-19 management were used for the neonate who was recovered and discharged. © 2021, TMU Press.
RESUMEN
This poem enters one of many craters left by the COVID-19 pandemic and bears witness to the divisions exposed within. © 2021 by the author(s).