A customized early warning score enhanced emergency department patient flow process and clinical outcomes in a COVID-19 pandemic.

Objective: Patient crowding and boarding in the emergency department (ED) is associated with adverse outcomes and has become increasingly problematic in recent years. We investigated the impact of an ED patient flow countermeasure using an early warning score. Methods: We conducted a cross-sectional analysis of observational data from patients who presented to the ED of a Level 1 Trauma Center in Pennsylvania. We implemented a modified version of the Modified Early Warning Score (MEWS), called mMEWS, to address patient flow. Patients aged ≥18 years old admitted to the adult hospital medicine service were included in the study. We compared the pre-mMEWS (February 19, 2017-February 18, 2019) to the post-mMEWS implementation period (February 19, 2019-June 30, 2020). During the intervention, low MEWS (0-1) scoring admissions went directly to the inpatient floor with expedited orders, the remainder waited in the ED until the hospital medicine admitting team evaluated the patient and then placed orders. We investigated the association between mMEWS, ED length of stay (LOS), and 24-hour rapid response team (24 hour-RRT) activation. RRT activation rates were used as a measure of adverse outcome for the new process and are a network team response for admitted patients who are rapidly decompensating. The association between mMEWS and the outcomes of ED length of stay in minutes and 24 hour-RRT activation was assessed using linear and logistic regression adjusting for a priori selected confounders, respectively. Results: Of the total 43,892 patients admitted, 19,962 (45.5%) were in the pre-mMEWS and 23,930 (54.5%) in the post-mMEWS implementation period. The median post-mMEWS ED LOS was shorter than the pre-mMEWS (376 vs 415 minutes; Conclusion: The use of a modified MEWS enhanced admission process to the hospital medicine service, even during the COVID-19 pandemic, was associated with a significant decrease in ED LOS without a significant increase in 24 hour-RRT activation

Reduced Expression of Fumarate Hydratase in Clear Cell Renal Cancer Mediates HIF-2α Accumulation and Promotes Migration and Invasion

Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Individuals with HLRCC are predisposed to the development of highly malignant and lethal renal cell carcinoma (RCC). The mechanisms of tumorigenesis proposed have largely focused on the biochemical consequences of loss of FH enzymatic activity. While loss of the tumor suppressor gene von Hippel Lindau (VHL) is thought to be an initiating event for the majority of RCCs, a role for FH in sporadic renal cancer has not been explored. Here we report that FH mRNA and protein expression are reduced in clear cell renal cancer, the most common histologic variant of kidney cancer. Moreover, we demonstrate that reduced FH leads to the accumulation of hypoxia inducible factor- 2α (HIF-2α), a transcription factor known to promote renal carcinogenesis. Finally, we demonstrate that overexpression of FH in renal cancer cells inhibits cellular migration and invasion. These data provide novel insights into the tumor suppressor functions of FH in sporadic kidney cancer

Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA hypermutation

金沢大学医薬保健研究域医学系Mitochondrial DNA (mtDNA) mutations are found in many types of cancers and suspected to be involved in carcinogenesis, although the mechanism has not been elucidated. In this study, we report that consecutive C-to-T mutations (hypermutations), a unique feature of mutations induced by APOBECs, are found in mtDNA from cervical dysplasia and oropharyngeal cancers. In vitro, we found that APOBEC3A (A3A) and 3B (A3B) expression, as well as mtDNA hypermutation, were induced in a cervical dysplastic cell line W12 when cultured in a differentiating condition. The ectopic expression of A3A or A3B was sufficient to hypermutate mtDNA. Fractionation of W12 cell lysates and immunocytochemical analysis revealed that A3A and A3B could be contained in mitochondrion. These results suggest that mtDNA hypermutation is induced upon keratinocyte differentiation, and shed light on its molecular mechanism, which involves A3s. The possible involvement of mtDNA hypermutations in carcinogenesis is also discussed. © 2018 The Author(s)