Risk Factors for E2SKAPE Infections and Mortality Among Liver Transplant Recipients.

PURPOSE: Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) plus Escherichia coli (E2SKAPE), in particular multidrug-resistant (MDR) E2SKAPE infections, occur frequently and pose a life-threatening to liver transplant (LT) recipients. To prevent E2SKAPE infections and improve the prognosis of LT recipients, the identification of risk factors for E2SKAPE infections and mortality is necessary. METHODS: E2SKAPE pathogens were isolated and identified from clinical samples following standard microbiological procedures. All episodes of E2SKAPE infections and mortality documented among LT recipients were analyzed. FINDINGS: A total of 83 episodes of E2SKAPE infections, including 75 (90.4%) episodes of MDR-E2SKAPE infections, occurred in 23.1% (53/229) of LT recipients. E. faecium was the dominant causative bacterium (37/83; 44.6%). The most common site of infections was the urinary tract (14/53; 26.4%). Sixteen (7%) patients died within 2 months after LT, and 7 deaths were E2SKAPE infections-related. Multivariate logistic regression analysis revealed that female sex [odds ratio (OR) = 3.665, 95% confidence interval (CI): 1.614-8.321, P = 0.002], duration of surgery ≥ 400 min [OR = 2.328, 95%CI: 1.151-4.707, P = 0.019], intraoperative red blood cell (RBC) transfusion ≥ 12U [OR = 2.542, 95%CI: 1.218-5.306, P = 0.013] and indwelling urethral catheter use ≥ 3 days [OR = 3.96, 95%CI: 1.309-11.981, P = 0.015] were independent risk factors for E2SKAPE infections after LT, and that only exposure to more than 2 intravenous antibiotics post-LT [OR = 0.318, 95%CI: 0.15-0.674, P = 0.003] was negatively associated with acquisition of E2SKAPE infections. The predictors of crude mortality included female sex [OR = 4.822, 95%CI: 1.299-17.904, P = 0.019], creatinine on day 3 post-LT > 1.5 mg/dL [OR = 11.014, 95%CI: 2.985-40.637, P < 0.001], mechanical ventilation post-LT [OR = 10.724, 95%CI: 2.695-42.676, P = 0.001] and recipients with E2SKAPE infections [OR = 4.112, 95%CI: 1.169-14.47, P = 0.028]. IMPLICATIONS: A high incidence of E2SKAPE infections was noted in the early post-LT period. The most common infection site was the urinary tract, and the dominant pathogenic bacterium was E. faecium. Female sex, prolonged surgery time, massive RBC transfusion, or delayed urethral catheter removal were associated with E2SKAPE infections. Only exposure to more than 2 intravenous antibiotics post-LT was negatively related to the acquisition of E2SKAPE infections. The predictors of mortality included female sex, creatinine on day 3 post-LT>1.5 mg/dL, mechanical ventilation post-LT, and recipients with E2SKAPE infections.

[Risk Factors and Prognosis of Delirium After Liver Transplantation].

Objective: To analyze the incidence, the onset time, and the risk factors of delirium after liver transplantation (LT). Methods: The clinical data of 211 patients who underwent LT at Third Xiangya Hospital, Central South University between January 2019 and December 2021 were collected to investigate the incidence and the onset time of postoperative delirium. Univariate analysis and multivariate logistic regression analysis were conducted to analyze the risk factors of delirium and to analyze the effect of delirium on clinical outcomes. Results: The incidence of delirium was 20.4% (43/211) and the median interval between LT and the onset of delirium was 19 hours. Univariate analysis showed that the preoperative Model for End-Stage Liver Disease (MELD) score≥22, preoperative length-of-stay≥7, liver cancer, preoperative hepatic encephalopathy, infections within 2 months before LT, preoperative lymphocyte value<0.5×10 9 L －1, massive amount of intraoperative red blood cell infusion, and carbapenem antibiotics use for 3 days or longer were associated with postoperative delirium. Multivariate logistic regression analysis showed that preoperative infections within 2 months before LT (odds ratio [ OR]=2.597, 95% confidence interval [ CI]: 1.135-5.944, P=0.024), preoperative MELD score≥22 ( OR=2.967, 95% CI: 1.104-7.975, P=0.031), and preoperative hepatic encephalopathy ( OR=4.700, 95% CI: 2.043-10.602, P<0.001) were independent risk factors for delirium after LT, while carbapenems antibiotics use for 3 days or longer ( OR=0.192, 95% CI: 0.083-0.441, P<0.001) was a protective factor for postoperative delirium among LT recipients. Regarding clinical outcomes, patients with delirium had longer postoperative ICU length-of-stays than those without delirium did ( P=0.025). Conclusion: There is a high incidence of postoperative delirium among patients who undergo LT and the onset time of delirium after LT is early. Risk factors include preoperative infections, high MELD score, and hepatic encephalopathy. On the other hand, the use of carbapenems can help prevent delirium.

The application of metagenomic next-generation sequencing in patients with infection or colonization caused by Lichtheimia species.

Background: Mucormycosis is considered the fourth most common invasive fungal disease after candidiasis, aspergillosis and cryptococcosis. Lichtheimia species accounted for 5%-29% of all mucormycosis. However, available data on species-specific analysis of Lichtheimia infections are limited. Methods: This study included nine patients hospitalized in five hospitals in two cities in south China with mucormycosis or colonization caused by Lichtheimia species, diagnosed mainly by metagenomic next-generation sequencing (mNGS). The corresponding medical records were reviewed, and the clinical data analyzed included demographic characteristics, site of infection, host factors and type of underlying disease, diagnosis, clinical course, management, and prognosis. Results: In this study, nine patients with Lichtheimia infections or colonization had a recent history of haematological malignancy (33.3%), solid organ transplants (33.3%), pulmonary disease (22.2%), and trauma (11.1%) and were categorized as 11.1% (one case) proven, 66.7% (six cases) probable mucormycosis and 22.2% (two cases) colonization. Pulmonary mucormycosis or colonization was the predominant presentation in 77.8% of cases and mucormycosis caused by Lichtheimia resulted in death in four out of seven patients (57.1%). Conclusion: These cases highlight the importance of early diagnosis and combined therapy for these sporadic yet life-threatening infections. Further studies on the diagnosis and control of Lichtheimia infection in China are required.

TMED2/9/10 Serve as Biomarkers for Poor Prognosis in Head and Neck Squamous Carcinoma.

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

Drug Resistance and Risk Factors for Acquisition of Gram-Negative Bacteria and Carbapenem-Resistant Organisms Among Liver Transplant Recipients.

INTRODUCTION: Infections caused by Gram-negative bacteria, in particular carbapenem-resistant organisms (CRO), pose a great threat to liver transplant (LT) recipients. Understanding the risk factors for Gram-negative and CRO infections and the drug resistance of corresponding bacteria will help guide the prevention and treatment of these infections. METHODS: Data on the composition, distribution and drug resistance of Gram-negative bacteria and CRO among LT recipients were collected. The risk factors for Gram-negative and CRO infections were identified via univariate and multivariate analysis. RESULTS: A total of 45 episodes of Gram-negative infection, including 20 episodes of CRO infection, occurred in 19.9% (27/136) of LT recipients. Klebsiella pneumoniae was the dominant pathogenic bacteria (14/45; 31.1%). The most common site of infection was the abdominal cavity/bile duct (11/27; 40.7%). Eleven (8.1%) patients died within 2 months after LT, and two deaths were related to Gram-negative infection. Gram-negative bacteria were relatively sensitive to tigecycline and polymyxin B, with resistance of 26.7 and 11.1%, respectively. CRO had lower resistance to ceftazidime/avibactam (45.5%) and polymyxin B (10%). A univariate analysis showed that male sex, infection within 2 months prior to LT, duration of surgery ≥ 400 min, reoperation, indwelling urethral catheter use ≥ 3 days and elevated alanine aminotransferase on day 1 post-LT were associated with Gram-negative infection. Multivariate logistic regression analysis revealed that infection within 2 months prior to LT [odds ratio (OR) = 4.426, 95%CI: 1.634-11.99, P = 0.003], duration of surgery ≥ 400 min [OR = 3.047, 95%CI: 1.194-7.773, P = 0.02] and indwelling urethral catheter use ≥ 3 days [OR = 5.728, 95%CI: 1.226-26.763, P = 0.026] were independent risk factors for Gram-negative infection after LT, and that only carbapenem use ≥ 3 days within 15 days prior to infection [OR = 14, 95%CI: 1.862-105.268, P = 0.01] was related to the occurrence of CRO infections. CONCLUSION: The incidence of Gram-negative and CRO infections was high in the early post-LT period. The most common infection site was the abdominal cavity/bile duct, and the dominant pathogen was K. pneumoniae. Patients with infections within 2 months prior to LT, prolonged surgery time or delayed urethral catheter removal were prone to Gram-negative infection. Carbapenem exposure was correlated with CRO infections.

Insulin alleviates LPS-induced ARDS via inhibiting CUL4B-mediated proteasomal degradation and restoring expression level of Na,K-ATPase α1 subunit through elevating HCF-1.

Acute respiratory distress syndrome (ARDS) is a critical disease with a high mortality rate, characterized by obstinate hypoxemia caused by accumulation of alveolar fluid and excessive uncontrolled inflammation. Na,K-ATPase α1 (ATP1A1) subunit is an important component of Na,K-ATPase that transports Na+ and K+ and scavenges alveolar fluid. The function of Na,K-ATPase is always impaired during ARDS and results in more severe symptoms of ARDS. However, the regulatory mechanism of Na,K-ATPase after ARDS remains unclear. Here, we revealed ATP1A1 was downregulated post-transcriptionally by an E3 ligase component CUL4B mediated proteasomal degradation. Moreover, we found insulin could inhibit the upregulation of CUL4B in an insulin receptor cofactor HCF-1-dependent manner. Our study resolved the molecular mechanism underlying the clearance impairment of alveolar fluid and provided a clue for the usage of insulin as a potential therapeutic medicine for ARDS.