The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.

Objective: Predictive tools such as the Glasgow Blatchford Score (GBS) and Pre-Rockall Score (PRS) have been used to foresee risks for gastrointestinal patients. This study was undertaken to determine the usefulness of the various available predictive tools in a vulnerable population. Methods: Data of patients with vulnerable upper gastrointestinal bleeding, who visited the emergency room from January 1, 2017 to December 31, 2018, were retrospectively examined. The GBS and PRS values were determined for all patients. Predictions of therapeutic endoscopy were evaluated with the area under curve (AUC) in the receiver operatory characteristic (ROC) curve. Results: A total of 152 patients were included in the study, 46 of whom required therapeutic endoscopes. In the area below the ROC curve, higher GBS values were obtained as compared to PRS in predicting therapeutic endoscopy (AUC, 0.726; 95% confidence interval [CI], 0.648-0.795 vs. 0.705; 95% CI, 0.626-0.776; P=0.689, respectively), transfusion (AUC, 0.861; 95% CI, 0.796-0.912 vs. 0.715; 95% CI, 0.637-0.786; P=0.001, respectively), and 30-day mortality (AUC, 0.698; 95% CI, 0.618-0.770 vs. 0.622; 95% CI, 0.540-0.699; P=0.351, respectively). Considering GBS 0, we determined with 100% sensitivity and 4.72% specificity that endoscopic treatment is redundant. Conclusion Compared to PRS, GBS excelled in predicting interventional treatment (endoscopy, transfusion) of vulnerable upper gastrointestinal patients, as well as the 30-day mortality. GBS is more useful in predicting low-risk patients that do not require treatment endoscopy, and is therefore a suitable procedure for outpatient care.

Objective: Predictive tools such as the Glasgow Blatchford Score (GBS) and Pre-Rockall Score (PRS) have been used to foresee risks for gastrointestinal patients. This study was undertaken to determine the usefulness of the various available predictive tools in a vulnerable population. Methods: Data of patients with vulnerable upper gastrointestinal bleeding, who visited the emergency room from January 1, 2017 to December 31, 2018, were retrospectively examined. The GBS and PRS values were determined for all patients. Predictions of therapeutic endoscopy were evaluated with the area under curve (AUC) in the receiver operatory characteristic (ROC) curve. Results: A total of 152 patients were included in the study, 46 of whom required therapeutic endoscopes. In the area below the ROC curve, higher GBS values were obtained as compared to PRS in predicting therapeutic endoscopy (AUC, 0.726; 95% confidence interval [CI], 0.648-0.795 vs. 0.705; 95% CI, 0.626-0.776; P=0.689, respectively), transfusion (AUC, 0.861; 95% CI, 0.796-0.912 vs. 0.715; 95% CI, 0.637-0.786; P=0.001, respectively), and 30-day mortality (AUC, 0.698; 95% CI, 0.618-0.770 vs. 0.622; 95% CI, 0.540-0.699; P=0.351, respectively). Considering GBS 0, we determined with 100% sensitivity and 4.72% specificity that endoscopic treatment is redundant. Conclusion Compared to PRS, GBS excelled in predicting interventional treatment (endoscopy, transfusion) of vulnerable upper gastrointestinal patients, as well as the 30-day mortality. GBS is more useful in predicting low-risk patients that do not require treatment endoscopy, and is therefore a suitable procedure for outpatient care.

OBJECTIVES: To report a case of toxic hepatitis in a worker exposed to a cleansing agent mainly composed of methylene chloride. METHODS: A 27-year-old female worker who had worked in an inspection and packing position of semiconductor parts in a factory using methylene chloride as a metal cleansing solvent was hospitalized due to fever, chill and generalized aches. We evaluated her with blood tests, abdominal ultrasonographic scan and abdominal CT scan and also took her occupational history. RESULTS: The patient showed acute hepatitis in blood and radiologic tests after admission. The serologic tests for viral hepatitis A, B, C and autoimmune hepatitis were negative. She had no history of significant alcohol use, recent medication or drug allergy. After admission, her symptoms were improved and liver enzyme levels(AST and ALT) were markedly reduced. She returned to her workplace after discharge. Thereafter, however, her previous symptoms were recurred and she was hospitalized again 2 days after returning to her workplace. After this second admission, she showed acute hepatitis in blood tests and her symptoms were improved and liver enzyme levels were markedly reduced with the same pattern as those of the first admission. On the 11th day of the second admission, liver enzyme levels were normalized and she was discharged from hospital. CONCLUSIONS: We presume that this patient`s liver injury was related to the methylene chloride presence at her workplace due to her clinical symptoms, blood tests, radiologic tests and occupational history.
Adult ; Detergents* ; Drug Hypersensitivity ; Drug-Induced Liver Injury* ; Female ; Fever ; Hematologic Tests ; Hepatitis ; Hepatitis A ; Hepatitis, Autoimmune ; Humans ; Liver ; Methylene Chloride* ; Semiconductors ; Serologic Tests ; Tomography, X-Ray Computed