Cytokine release syndrome following durvalumab and tremelimumab in advanced hepatocellular carcinoma: A case report with cytokine and damage-associated molecular pattern analysis.

Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell hyperactivation caused by therapeutic agents, pathogens, cancers, and autoimmune diseases. In recent years, CRS has emerged as a rare, but significant, immune-related adverse event linked to immune checkpoint inhibitor therapy. Furthermore, several previous studies suggested that damage-associated molecular patterns (DAMPs) could be involved in malignancy-related CRS. In this study, we present a case of severe CRS following combination therapy with durvalumab and tremelimumab for advanced hepatocellular carcinoma, which recurred during treatment, as well as an analysis of cytokine and DAMPs trends. A 35-year-old woman diagnosed with hepatocellular carcinoma underwent a partial hepatectomy. Due to cancer recurrence, she started a combination of durvalumab and tremelimumab. Then, 29 days post-administration, she developed fever and headache, initially suspected as sepsis. Despite antibiotics, her condition worsened, leading to disseminated intravascular coagulation and hemophagocytic syndrome. The clinical course and elevated serum interleukin-6 levels led to a CRS diagnosis. Steroid pulse therapy was administered, resulting in temporary improvement. However, she relapsed with increased interleukin-6, prompting tocilizumab treatment. Her condition improved, and she was discharged on day 22. Measurements of inflammatory cytokines interferon-γ, tumor necrosis factor-α, and DAMPs, along with interleukin-6, using preserved serum samples, confirmed marked elevation at CRS onset. CRS can occur after the administration of any immune checkpoint inhibitor, with the most likely trigger being the release of DAMPs associated with tumor collapse.

[Activity based costs of different units in a high complexity Chilean hospital]. / Los costos basados en actividades de Unidades Médico Quirúrgica y de Cuidados Medios en un hospital público.

BACKGROUND: Hospitals must have management tools that allow them to fulfil all their requirements with the allocated resources. AIM: To evaluate the number of bed-days according to the discharge diagnosis in a High Complexity Hospital in Chile. MATERIAL AND METHODS: An activity Based Cost (ABC) calculation was used. The stages were gathering of procedures, identification of the resources used, analysis of discharge diagnosis, definition of cost objects, resource cost drivers, cost of procedures, procedures cost drivers and cost of the cost objects that corresponds to bed-day by each medical specialty. Costs were calculated for Medical-Surgical and Intermediate Care units. RESULTS: There were significant differences in costs according to medical specialty when comparing the costs obtained using the Management information system (WinSig) and ABC. Respiratory, Renal and Circulatory-Cardiovascular specialties accounted for the most expensive bed-days. CONCLUSIONS: This study identified bed-day costs and provides disaggregated information about the causes of cost differences between medical specialties.

Los costos basados en actividades de Unidades Médico Quirúrgica y de Cuidados Medios en un hospital público / Activity based costs of different units in a high complexity Chilean hospital

Background: Hospitals must have management tools that allow them to fulfil all their requirements with the allocated resources. Aim: To evaluate the number of bed-days according to the discharge diagnosis in a High Complexity Hospital in Chile. Material and Methods: An activity Based Cost (ABC) calculation was used. The stages were gathering of procedures, identification of the resources used, analysis of discharge diagnosis, definition of cost objects, resource cost drivers, cost of procedures, procedures cost drivers and cost of the cost objects that corresponds to bed-day by each medical specialty. Costs were calculated for Medical-Surgical and Intermediate Care units. Results: There were significant differences in costs according to medical specialty when comparing the costs obtained using the Management information system (WinSig) and ABC. Respiratory, Renal and Circulatory-Cardiovascular specialties accounted for the most expensive bed-days. Conclusions: This study identified bed-day costs and provides disaggregated information about the causes of cost differences between medical specialties.