ABSTRACT
Soft tissue sarcomas (STS) are a rare disease with high recurrence rates and poor prognosis. Missing therapy options together with the high heterogeneity of this tumor type gives impetus to the development of individualized treatment approaches. This study identifies potential tumor antigens for the development of mRNA tumor vaccines for STS and explores potential immune subtypes, stratifying patients for immunotherapy. RNA-sequencing data and clinical information were extracted from 189 STS samples from The Cancer Genome Atlas (TCGA) and microarray data were extracted from 103 STS samples from the Gene Expression Omnibus (GEO). Potential tumor antigens were identified using cBioportal, the Oncomine database, and prognostic analyses. Consensus clustering was used to define immune subtypes and immune gene modules, and graph learning-based dimensionality reduction analysis was used to depict the immune landscape. Finally, four potential tumor antigens were identified, each related to prognosis and antigen-presenting cell infiltration in STS: HLTF, ITGA10, PLCG1, and TTC3. Six immune subtypes and six gene modules were defined and validated in an independent cohort. The different immune subtypes have different molecular, cellular, and clinical characteristics. The immune landscape of STS reveals the immunity-related distribution of patients and intra-cluster heterogeneity of immune subtypes. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination, and provides a reference for promoting individualized immunotherapy.
ABSTRACT
BACKGROUND: During the COVID-19 pandemic, Central COVID-19 Coordination Centers (CCCCs) have been established at several hospitals across Germany with the intention to assist local health care professionals in efficiently referring patients with suspected or confirmed SARS-CoV-2 infection to regional hospitals and therefore to prevent the collapse of local health system structures. In addition, these centers coordinate interhospital transfers of patients with COVID-19 and provide or arrange specialized telemedical consultations. OBJECTIVE: This study describes the establishment and management of a CCCC at a German university hospital. METHODS: We performed economic analyses (cost, cost-effectiveness, use, and utility) according to the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) criteria. Additionally, we conducted a systematic review to identify publications on similar institutions worldwide. The 2 months with the highest local incidence of COVID-19 cases (December 2020 and January 2021) were considered. RESULTS: During this time, 17.3 requests per day were made to the CCCC regarding admission or transfer of patients with COVID-19. The majority of requests were made by emergency medical services (601/1068, 56.3%), patients with an average age of 71.8 (SD 17.2) years were involved, and for 737 of 1068 cases (69%), SARS-CoV-2 had already been detected by a positive polymerase chain reaction test. In 59.8% (639/1068) of the concerned patients, further treatment by a general practitioner or outpatient presentation in a hospital could be initiated after appropriate advice, 27.2% (291/1068) of patients were admitted to normal wards, and 12.9% (138/1068) were directly transmitted to an intensive care unit. The operating costs of the CCCC amounted to more than 52,000 (US $60,031) per month. Of the 334 patients with detected SARS-CoV-2 who were referred via EMS or outpatient physicians, 302 (90.4%) were triaged and announced in advance by the CCCC. No other published economic analysis of COVID-19 coordination or management institutions at hospitals could be found. CONCLUSIONS: Despite the high cost of the CCCC, we were able to show that it is a beneficial concept to both the providing hospital and the public health system. However, the most important benefits of the CCCC are that it prevents hospitals from being overrun by patients and that it avoids situations in which physicians must weigh one patient's life against another's.