Evaluating prognostic indicators for in-hospital mortality in Fournier's gangrene: a 7-year study in a tertiary hospital.

BACKGROUND: Fournier's Gangrene Scoring Index (FGSI), Simplified FGSI (SFGSI), Uludag FGSI (UFGSI), Laboratory Risk Indicator for Necrotizing (LRINEC), Neutrophil-Lymphocyte ratio (NLR), and Platelet-lymphocyte ratio (PLR) have been devised to assess the risk of mortality in Fournier's Gangrene (FG) patients. However, the effectiveness of these indicators in predicting mortality at the time of admission remains uncertain. The aim of this study is to assess the prognostic efficacy of FG's various indicators on in-hospital mortality. METHODS: This study analyzed 123 patients from Dr. Soetomo General Hospital's emergency department in Indonesia from 2014 to 2020. Data included demographics, wound cultures, and parameters like FGSI, UFGSI, SFGSI, NLR, PLR, and LRINEC. In-hospital mortality status was also recorded. The data was subjected to comparative, sensitivity, specificity and regression analyses. RESULTS: In our study of 123 patients, the median age was 52, with a mortality rate of 17.9%. The majority of patients were male (91.1%) and the most common location was scrotal (54.5%). Non-survivors had a shorter median stay (6.5 days) compared to survivors (14 days). Diabetes was the most prevalent comorbidity (61.8%). The highest sensitivity and specificity were found in FGSI and UFGSI indicators. Multivariate logistic regression identified LoS and FGSI as independent predictors of mortality. CONCLUSIONS: FGSI and UFGSI, upon admission, demonstrated the highest sensitivity and specificity, with hospital stay duration and FGSI as key mortality determinants.

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice.

Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM-type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic ß cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic ß cells. It induces ß cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic ß cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic ß cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

The Cross-Talk Between the TNF-α and RASSF-Hippo Signalling Pathways.

The regulation of cell death through apoptosis is essential to a number of physiological processes. Defective apoptosis regulation is associated with many abnormalities including anomalies in organ development, altered immune response and the development of cancer. Several signalling pathways are known to regulate apoptosis including the Tumour Necrosis Factor-α (TNF-α) and Hippo signalling pathways. In this paper we review the cross-talk between the TNF-α pathway and the Hippo signalling pathway. Several molecules that tightly regulate the Hippo pathway, such as members of the Ras-association domain family member (RASSF) family proteins, interact and modulate some key proteins within the TNF-α pathway. Meanwhile, TNF-α stimulation also affects the expression and activation of core components of the Hippo pathway. This implies the crucial role of signal integration between these two major pathways in regulating apoptosis.