Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis.

Importance: Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited. Objective: To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis. Design, Setting, and Participants: This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022. Exposure: An SQ insulin treatment protocol for diabetic ketoacidosis. Main Outcomes and Measures: Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care. Results: A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death. Conclusions and Relevance: These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.

TGF-ß2: A Novel Target of CD44-Promoted Breast Cancer Invasion.

We have developed a tetracycline (tet)-off regulated expression of CD44s gene in the breast cancer (BC) cell line MCF-7 (B5 clone) and identified TGF-ß2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates, collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA. Our results showed that TGF-ß2 mRNA levels were significantly elevated following the removal of tetracycline at 18, 24, and 48 h post-HA stimulation compared to the parental cells. Furthermore, the TGF-ß2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tetracycline. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-ß2 expression upon HA-stimulation, and subsequently inhibited BC cell invasion in vitro. In addition to identifying TGF-ß2 as a target for HA/CD44 signaling, this data suggests that ATF/CREB might be a potential transcription factor linking HA/CD44 activation to TGF-ß2 transcription and additional experiments are required for a better understanding of the molecular mechanisms underpinning the novel function of the CD44/ TGF-ß2 signaling pathway in breast cancer metastasis.