Acute Phlegmonous Gastritis Complicated by Subphrenic Abscess.

BACKGROUND: Phlegmonous gastritis (PG) is a rare and potentially fatal disease characterized by bacterial infection of the gastric wall. However, its clinical features are nonspecific, which may delay its diagnosis and treatment. CASE REPORT: We report a case of a previously healthy 53-year-old woman with localized PG complicated by subphrenic abscess formation who was treated successfully with antibiotics and percutaneous catheter drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early diagnosis and treatment initiation are important to improving outcomes. Emergency physicians should consider PG a differential diagnosis of acute abdomen.

Serum cholesterol as a predictor of mortality among the elderly patients with pneumonia in the emergency department.

BACKGROUND: Reduced cholesterol levels are associated with poor outcomes in critically ill patients. However, the effect of reduced cholesterol levels on the prognosis of patients with community-acquired pneumonia (CAP) is unclear. This study aimed to investigate the association between serum total cholesterol levels and the clinical outcomes of elderly patients with CAP. METHODS: This was a retrospective observational study that included elderly (≥65 years) CAP patients hospitalized through emergency department between January 2016 and December 2019. We collected their baseline characteristics and laboratory data, including total cholesterol levels at the time of admission. Univariate and multivariate analyses were performed to determine the association between total cholesterol levels and 14-day in-hospital mortality. RESULTS: A total of 380 patients were included. The overall 14-day in-hospital mortality rate was 12.37%. Survivors had higher total cholesterol levels than non-survivors (median, 125 mg/dL; interquartile range [IQR], 102-151 mg/dL versus median, 100 mg/dL; IQR, 83-126 mg/dL; p < 0.001). Multivariate analysis using a logistic regression model showed that a total cholesterol level of <97 mg/dL was independently associated with 14-day in-hospital mortality in patients with CAP (odds ratio, 2.93; 95% confidence interval, 1.13-7.599; p = 0.027). CONCLUSIONS: A decreased level of total cholesterol was associated with increased short-term mortality in elderly patients with CAP. Initial total cholesterol levels may be a useful biomarker to predict the outcome of patients with CAP.

Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2.

The mammalian target of rapamycin (mTOR) is a major component of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway that is dysregulated in 50% of all human malignancies. Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Here, we report WYE-125132 (WYE-132), a highly potent, ATP-competitive, and specific mTOR kinase inhibitor (IC(50): 0.19 +/- 0.07 nmol/L; >5,000-fold selective versus PI3Ks). WYE-132 inhibited mTORC1 and mTORC2 in diverse cancer models in vitro and in vivo. Importantly, consistent with genetic ablation of mTORC2, WYE-132 targeted P-AKT(S473) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1 activity biomarker P-AKT(T308), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells. Compared with the rapalog temsirolimus/CCI-779, WYE-132 elicited a substantially stronger inhibition of cancer cell growth and survival, protein synthesis, cell size, bioenergetic metabolism, and adaptation to hypoxia. Oral administration of WYE-132 to tumor-bearing mice showed potent single-agent antitumor activity against MDA361 breast, U87MG glioma, A549 and H1975 lung, as well as A498 and 786-O renal tumors. An optimal dose of WYE-132 achieved a substantial regression of MDA361 and A549 large tumors and caused complete regression of A498 large tumors when coadministered with bevacizumab. Our results further validate mTOR as a critical driver for tumor growth, establish WYE-132 as a potent and profound anticancer agent, and provide a strong rationale for clinical development of specific mTOR kinase inhibitors as new cancer therapy.