The Equipoise Between the Treatment of Glioblastoma and the Risk of Secondary Acute Myelogenous Leukemia: An Illustrative Case Report.

We present a case report of a 56-year-old woman who was diagnosed with biopsy-proven left thalamic glioblastoma multiforme (GBM). She was treated with standard concurrent chemotherapy and radiation, as well as a 2-year period of adjuvant temozolomide. She relapsed 2 ½ years after starting her initial therapy and was treated with bevacizumab and lomustine, but she relapsed. She was then placed on a phase 1/2 clinical trial that included KHK2455 and mogamulizumab-kpkc individually and in combination for almost 4 years. She had a rapid demise due to the development of a neutropenic pneumonia and treatment-induced acute myeloid leukemia (AML) and elected for hospice care.

The Cook Score: A Novel Assessment for the Prediction of Liver-Associated Clinical Events in a Diverse Population.

BACKGROUND AND AIMS: Transient elastography (TE) provides accurate quantification of liver fibrosis. Its usefulness could be significantly amplified in terms of predicting liver-associated clinical events (LACE). Our aim was to create a model that accurately predicts LACE by combining the information provided by TE with other variables in patients with chronic liver disease (CLD). METHODS: We retrospectively reviewed the electronic medical records of patients who underwent liver elastography, at John H. Stroger Hospital in Cook County, Chicago, IL. The incidences of LACE were documented including decompensation of CLD, new hepatocellular carcinoma, and liver-associated mortality. Significant predicting factors were identified through a forward stepwise Cox regression model. We used the beta-coefficients of these risk factors to construct the Cook Score for prediction of LACE. Receiver-operating characteristic (ROC) curves were plotted for Cook Score to evaluate its efficiency in prediction, in comparison with MELD-Na Score and FIB-4 Score. RESULTS: A total of 3097 patients underwent liver elastography at our institution. Eighty-eight LACE were identified. Age (hazard ratio (HR) 1.04, p = 0.002), aspartate aminotransferase to alanine aminotransferase ratio (HR 2.61, p < 0.001), platelet count (HR 0.98, p < 0.001), international normalized ration (INR) (HR 17.80, p < 0.001), and liver stiffness measurement (HR1.04, p < 0.001) were identified as significant predictors. The Cook Score was constructed with two optimal cut-off points to stratify patients into low-, intermediate-, and high-risk groups for LACE. The Cook Score proved superior than MELD-Na Score and FIB4 Score in predicting LACE with an area under curve of 0.828. CONCLUSION: This novel score based on a large robust sample would provide accurate prediction of prognosis in patients with chronic liver disease and guide individualized surveillance strategy once validated with future studies.

Gut derived-endotoxin contributes to inflammation in severe ischemic acute kidney injury.

BACKGROUND: Recent researches indicate that the intestinal consequences of renal ischemia reperfusion (IR) would predispose to the translocation of gut-derived endotoxin. Here, we designed experiments to test the hypothesis that the gut-derived endotoxin has a potential role in mediating local inflammatory processes in the acutely injured kidney. METHODS: Rats were performed sham or renal IR surgery (60 min of bilateral renal ischemia, then 24 h of reperfusion) (n = 5). The intestinal structural and mucosa permeability were evaluated. Serum endotoxin and bacterial load in liver and mesenteric lymph nodes (MLN) were measured. Separate groups were pretreated with oral norfloxacin 20 mg/kg/day or saline for 4 weeks and divided into sham plus saline, sham plus norfloxacin, renal IR plus saline and renal IR plus norfloxacin group. Serum biochemistry and endotoxin were determined. Kidney pathological changes were scored. Protein or mRNA expression of toll-like receptor 4 (TLR4) and proinflammatory mediators were measured in kidney homogenate. RESULTS: Renal IR led to marked intestinal integrity disruption and increase in intestinal permeability. These are accompanied by low grade of endotoxemia as well as increased bacterial load in liver and MLN. The group pretreated with norfloxacin showed significant attenuation of the increase in serum urea, ALAT, ASAT and endotoxin. The increased renal protein or mRNA of TLR4 and proinflammatory mediators (IL-6 and MCP-1) in the unpretreated animals was significantly attenuated in the norfloxacin-pretreated animals. However, norfloxacin pretreatment did not produce any protective effects on renal tubular integrity. CONCLUSIONS: Our results show for the first time that gut-derived endotoxin, resulting from an increased intestinal permeability after severe renal IR, subsequently amplifies intrarenal inflammatory response by activation renal TLR4 signaling. Our study results do not establish that antibiotic administration was effective in improving the overall renal outcome. However, our findings may be the first step to understanding how to tailor therapies to mitigate intrarenal inflammation in select groups of patients.