Septic Shock Short-Term Outcomes in Patients With Psychiatric Disorders: Analysis From the National Inpatient Sample Database.

BACKGROUND: Major psychiatric disorders are associated with lower life expectancy primarily due to comorbid illnesses and suboptimal access to health care. Large-scale contemporary data in the United States on in-hospital mortality of patients with major psychiatric disorder and sepsis are lacking. OBJECTIVE: To describe the short-term outcomes of hospitalized patients with major psychiatric disorders and septic shock. METHODS: We performed a retrospective cohort study using the National Inpatient Sample database from 2016 to 2019 to identify septic shock hospitalizations in patients with versus without major psychiatric disorder (defined as schizophrenia and affective disorders). Baseline variables and in-hospital mortality trends were compared between the 2 groups. RESULTS: Out of 1,653,255 hospitalizations with septic shock identified between 2016 and 2019, 16.2% had a diagnosis of major psychiatric disorder as defined above. After adjusting for various patient-level and hospital-level demographics and coexisting clinical conditions in a multivariable logistic regression, the odds of in-hospital mortality in patients with any major psychiatric disorder were 0.71 times that of those without a diagnosis of psychiatric illness (95% confidence interval [CI], 0.69-0.73; P < 0.001). Similarly, when the disorders were divided into 2 categories for subanalysis, those with schizophrenia had 38% lower odds of dying compared to those without schizophrenia (adjusted odds ratio, 0.62; 95% CI, 0.58-0.66; P < 0.001). Those with affective disorders had 25% lower odds of in-hospital mortality than those without a diagnosis of an affective disorder (adjusted odds ratio, 0.75; 95% CI, 0.73-0.77; P < 0.001). The adjusted mean length of stay for those diagnosed with major psychiatric disorder was 0.38 days longer than those without significant psychiatric illness (95% CI, 0.28-0.49; P < 0.001). On the other hand, the mean hospitalization charges were $10,516 less for patients with a major psychiatric disorder compared to those without (95% CI, -$11,830 to -$9,201; P < 0.001). CONCLUSIONS: Hospitalized patients with major psychiatric disorder and septic shock had lower risk of short-term mortality. Further studies are needed to examine the reasons behind this lower in-hospital mortality risk.

Re-expression of miR-200 by novel approaches regulates the expression of PTEN and MT1-MMP in pancreatic cancer.

Membrane type-1 matrix metalloproteinase (MT1-MMP) is often activated and expressed in tumor cells with significant invasive properties, and is associated with poor prognosis of patients. This could partly be due to deregulated expression of microRNAs (miRNAs) which regulates the expression of MT1-MMP and PTEN (phosphatase and tensin homolog) contributing to tumor invasion and metastasis. We initially compared the expression profile of miR-200 family, PTEN and MT1-MMP expression in six pancreatic cancer (PC) cell lines by qRT-PCR and western blot analysis. We found loss of expression of miR-200a, b and c in chemo-resistant PC cell lines, which was correlated with loss of PTEN and over-expression of MT1-MMP. Based on our initial findings, we chose BxPC-3, MIAPaCa-2 and MIAPaCa-2-GR cells for further mechanistic studies We assessed the effect of two separate novel agents CDF (a synthetic analog of curcumin) and BR-DIM (a natural agent) on PC cells. The expression of miR-200 family and PTEN was significantly re-expressed whereas the expression of MT1-MMP was down-regulated by CDF and BR-DIM treatment. Forced over-expression or silencing of miR-200c, followed by either CDF or BR-DIM treatment of MIAPaCa-2 cells, altered the morphology of cells, wound-healing capacity, colony formation and the expression of MT1-MMP and PTEN. These results provide strong experimental evidence showing that the loss of miR-200 family and PTEN expression and increased level of MT1-MMP leads to aggressive behavior of PC cells, which could be attenuated through re-expression of miR-200c by CDF and/or BR-DIM treatment, suggesting that these agents could be useful for PC treatment.