A prognostic assessment predicated by blood culture-based bacteria clustering from real-world evidence: Novel strategies and perspectives on prevention and management of sepsis.

Sepsis, a syndrome with disturbed host response to severe infection, is a critical health problem worldwide. It is urged to develop and update novel therapeutic strategies for improving the outcome of sepsis. In this study, we demonstrated that different bacteria clustering in sepsis patients may generate differences of prognosis results. We extracted all the sepsis patients from Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) critical care data set according to certain standards and clinical score, a total of 2,339 patients were included in our study. Then we used multiple data analytics and machine learning methods to make all data deeply analyzed and elucidated. The results showed that the types of bacteria infected by patients with different ages, sex and race are different, the types of bacteria infected by patients with different SIRS values and GCS scores of the first day are different, and the severity of patients with different clusters is different, and most importantly, the survival rate of patients with different clusters also has this significant difference. We concluded prognostic assessment predicated by bacteria clustering might be a relatively potentially novel strategies and perspectives on prevention and management for sepsis in the future.

Mesenchymal stem cell-derived exosome alleviates sepsis- associated acute liver injury by suppressing MALAT1 through microRNA-26a-5p: an innovative immunopharmacological intervention and therapeutic approach for sepsis.

Background: Sepsis is a syndrome with the disturbed host response to severe infection and is a major health problem worldwide. As the front line of infection defense and drug metabolism, the liver is vulnerable to infection- or drug-induced injury. Acute liver injury (ALI) is thus common in patients with sepsis and is significantly associated with poor prognosis. However, there are still few targeted drugs for the treatment of this syndrome in clinics. Recent studies have reported that mesenchymal stem cells (MSCs) show potential for the treatment of various diseases, while the molecular mechanisms remain incompletely characterized. Aims and Methods: Herein, we used cecal ligation puncture (CLP) and lipopolysaccharide (LPS) plus D-galactosamine (D-gal) as sepsis-induced ALI models to investigate the roles and mechanisms of mesenchymal stem cells (MSCs) in the treatment of ALI in sepsis. Results: We found that either MSCs or MSC-derived exosome significantly attenuated ALI and consequent death in sepsis. miR-26a-5p, a microRNA downregulated in septic mice, was replenished by MSC-derived exosome. Replenishment of miR-26a-5p protected against hepatocyte death and liver injury caused by sepsis through targeting Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), a long non-coding RNA highly presented in hepatocyte and liver under sepsis and inhibiting anti-oxidant system. Conclusion: Taken together, the results of the current study revealed the beneficial effects of MSC, exosome or miR-26a-5p on ALI, and determined the potential mechanisms of ALI induced by sepsis. MALAT1 would be a novel target for drug development in the treatment of this syndrome.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

Z-DNA binding protein 1 promotes heatstroke-induced cell death.

Heatstroke is a heat stress-induced, life-threatening condition associated with circulatory failure and multiple organ dysfunctions. If global warming continues, heatstroke might become a more prominent cause of mortality worldwide, but its pathogenic mechanism is not well understood. We found that Z-DNA binding protein 1 (ZBP1), a Z-nucleic acid receptor, mediated heatstroke by triggering receptor-interacting protein kinase 3 (RIPK3)-dependent cell death. Heat stress increased the expression of ZBP1 through heat shock transcription factor 1 (HSF1) and activated ZBP1 through a mechanism independent of the nucleic acid sensing action. Deletion of ZBP1, RIPK3, or both mixed lineage kinase domain-like (MLKL) and caspase-8 decreased heat stress-induced circulatory failure, organ injury, and lethality. Thus, ZBP1 appears to have a second function that orchestrates host responses to heat stress.

Bibliometric Analysis of 100 Top-Cited Articles in Gastric Disease.

OBJECTIVES: The bibliometric analysis uses the citation count of an article to measure its impact in the scientific community, yet there is still no comprehensive summary of gastric disease researches via bibliometric analysis. We aimed to evaluate the situations and trends of the most cited articles in gastric disease via bibliometric analysis and to provide physicians a practical guide in assessing the most influential articles written on this subject. METHODS: The 100 top-cited articles in gastric disease were compiled using Web of Science. The articles selected were evaluated for their number of citations, year of publication, country of origin, type of study, and others. RESULTS: The database had 484,281 articles published between 1965 and 2019. The most cited article received 4,017 citations and the least received 604, with a mean of 1,149 citations. We classified the articles into seven categories: gastric cancer (n = 53), Helicobacter pylori (n = 17), ulcer (n = 7), gastrointestinal stromal tumors (n = 6), gastritis (n = 5), gastric bypass surgery (n = 2), and others (n = 10). Altogether, 69 of the articles were from the USA (n = 41), the UK (n = 17), and Japan (n = 11). Among all the institutions, Royal Perth Hospital led the list with 5 articles. One-quarter of authors owned three or more of these top-cited articles. The 100 papers were published in 33 journals, and most of them were clinical researches (n = 47). CONCLUSIONS: Our study provides a historical perspective for the scientific progress of gastric disease, and the articles of significant findings that contributed great impact on the prevention and treatment of gastric disease had been identified.

Efficacy of prednisone for prevention of esophageal stricture after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Our objective was to investigate the efficacy and safety of oral prednisone for the prevention of esophageal stricture formation after endoscopic submucosal dissection (ESD) in an optimal administration program. METHODS: Patients who underwent circumferential or semi-circumferential (more than three quarters but not a complete circular) ESD for esophageal squamous cell carcinoma were eligible for this study. Oral prednisolone was administered to the study group at a dose of 30 mg/day on the third day post-ESD, and then tapered gradually (30, 25, 20, 15, 10, and 5 mg for 14 days). Serial esophagoscopy with iodine staining was performed to assess stenosis and tumor recurrence at one, three, six, and 12 months after ESD. Endoscopic balloon dilatation was performed whenever patients experienced persistent dysphagia to solids. Data were statistically analyzed. RESULTS: Twenty-three patients (15 men, mean age 66.6 years) were enrolled in the study. Post-procedural esophageal stricture was significantly lower in the study group (23.1%) compared to the control (80%) (P < 0.05). A significantly higher number of endoscopic balloon dilatation sessions were performed (P < 0.05) in the control (13.5) than in the study group (0.69). There were no adverse events related to oral prednisolone or the procedure itself and no treatment-related mortality was observed during the 12 month follow-up. CONCLUSIONS: Our study suggested an optimal administration program of oral prednisone therapy and demonstrated that it is safe and effective for the prevention of esophageal stricture in patients after complete or semi-circular ESD for esophageal squamous cell carcinoma.

Oncogenic NRAS hyper-activates multiple pathways in human cord blood stem/progenitor cells and promotes myelomonocytic proliferation in vivo.

Oncogenic NRAS mutations are prevalent in human myeloid leukemia, especially in chronic myelomonocytic leukemia (CMML). NrasG12D mutation at its endogenous locus in murine hematopoietic stem cells (HSCs) leads to CMML and acute T-cell lymphoblastic lymphoma/leukemia in a dose-dependent manner. Hyper-activated MAPK and STAT5 pathways by oncogenic Nras contribute to the leukemogenesis in vivo. However, it is unclear whether these conclusions remain true in a more human relevant model. Here, we evaluated the effects of NRASG12D on human hematopoiesis and leukemogenesis in vitro and in vivo by ectopically expressing NRASG12D in human cord blood stem/progenitor cells (hSPCs). NRASG12D expressing hSPCs preferentially differentiated into myelomonocytic lineage cells, demonstrated by forming more colony forming unit-macrophages than control hSPCs in cultures. Transplantation of NRASG12D expressing hSPCs initiated myeloproliferative neoplasm in immune deficiency mice. All the recipient mice died of myeloid tumor burdens in spleens and bone marrows and none developed lymphoid leukemia. Phospho-flow analysis of CD34(+) CD38(-) hSPCs confirmed that NRASG12D hyper-activated MAPK, AKT and STAT5 pathways. Our study provides the strong evidence that NRASG12D mutation mainly targets monocytic lineage cells and leads to myelomonocytic proliferation in vivo in a highly human relevant context.