An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Efficacy and safety of colistin sulfate in the treatment of infections caused by carbapenem-resistant organisms: a multicenter retrospective cohort study.

Background: Polymyxins have become an important treatment option for carbapenem-resistant organisms (CRO) infections. However, there is a rare of clinical studies on colistin sulfate. This study sought to investigate the rate of clinical improvement and adverse reactions of colistin sulfate in the treatment of severe infections caused by CRO in critically ill patients and assess the factors associated with 28-day all-cause mortality. Methods: This multicenter retrospective cohort study included intensive care unit (ICU) patients who received colistin sulfate due to CRO infections during July 2021 and May 2022. The primary endpoint was clinical improvement at end of therapy. Secondary endpoints included adverse reactions bacterial clearance rate and 28-day all-cause mortality. Results: A total of 122 patients, who were included between July 2021 and May 2022, were included in this study, of whom 86 (70.5%) showed clinical improvement and 36 (29.5%) showed clinical failure. The comparison of the clinical data of the patients showed that the median sequential organ failure assessment (SOFA) score was higher in the failure group than the improvement group {9.5 [7, 11] vs. 7 [4, 9], P=0.002}, the proportion of patients receiving extracorporeal membrane oxygenation (ECMO) was higher in the failure group than the improvement group (27.8% vs. 12.8%, P=0.046), and the median duration of treatment was longer in the improvement group than the failure group {12 [8, 15] vs. 5.5 [4, 9.75], P<0.001}. A total of 5 (4.1%) patients suffered from acute kidney injury due to increases in creatinine during colistin sulfate treatment. The Cox regression survival analysis showed that the SOFA score [hazards ratio (HR) =1.198, P=0.001], ECMO treatment (HR =2.373, P=0.029), and duration of treatment (HR =0.736, P<0.001) were independently associated with 28-day all-cause mortality. Conclusions: Colistin sulfate is a reasonable choice for the treatment of CRO infections in the current treatment options are limited. The possible kidney injury caused by the colistin sulfate requires intensive monitoring.

circFLNA promotes intestinal injury during abdominal sepsis through Fas-mediated apoptosis pathway by sponging miR-766-3p.

BACKGROUND: Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. METHODS: We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. RESULTS: circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. CONCLUSION: Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.

Plasma concentrations of Colistin sulfate in a patient with septic shock on extracorporeal membrane oxygenation and continuous renal replacement therapy: a case report.

Background: Polymyxins antibiotics have become the first-line clinical drugs in the treatment of refractory gram-negative bacterial infections. Currently, there is a lack of clinical studies on the effect of extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) on polymyxin concentrations. The purpose of this report was to investigate the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT and to provide drug administration programs for critically ill patients receiving ECMO and CRRT. Case Description: In this case report, a patient with septic shock caused by severe acute pancreatitis, with abdominal pain and dyspnea as the main manifestations, was treated with ECMO combined with CRRT for life support and multiple anti-infective drugs. However, the symptoms of infection had not got improved, the inflammatory indicators remain high and the body temperature fluctuates repeatedly 36.7-38.5 ℃, was considered as carbapenem-resistant organisms (CROs) infection, and was empirically given Colistin sulfate for anti-infection treatment. Finally, the patient's condition improved and ECMO and CRRT were gradually withdrawn. At the same time, the plasma concentrations of Colistin sulfate before and after ECMO combined with CRRT, was monitored to determine the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT. Trough and peak concentrations on the 4th day of venovenous ECMO (VV-ECMO) combined with CRRT were 0.36 and 0.98 mg/L, respectively. After withdrawal of ECMO and CRRT, the concentrations were, respectively, 0.27 and 0.34 mg/L for trough concentrations, and 0.82 and 0.98 mg/L for peak concentrations. The data showed that there were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. No adverse effects occurred during follow-up. Conclusions: There were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. Therefore, no dose modification is required for Colistin sulfate in patients receiving ECMO with CRRT.

Identification of Key Immune-Related Genes in the Progression of Septic Shock.

Objective: Septic shock is the severe complication of sepsis, with a high mortality. The inflammatory response regulates the immune status and mediates the progression of septic shock. In this study, we aim to identify the key immune-related genes (IRGs) of septic shock and explore their potential mechanism. Methods: Gene expression profiles of septic shock blood samples and normal whole blood samples were retrieved from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression Portal (GTEx). The differential expression genes (DEGs) and septic shock-specific immune-related genes (SSSIRGs) were evaluated and identified, along with the immune components by "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT, version x)" algorithm. Additionally, in order to explore the key regulatory network, the relationship among SSSIRGs, upstream transcription factors (TFs), and downstream signaling pathways were also identified by Gene Set Variation Analysis (GSVA) and co-expression analysis. Moreover, the Connectivity Map (CMap) analysis was applied to find bioactive small molecules against the members of regulation network while Chromatin Immunoprecipitation sequencing (ChIP-seq) and Assay for Targeting Accessible-Chromatin with high-throughput sequencing (ATAC-seq) data were used to validate the regulation mechanism of the network. Results: A total of 14,843 DEGs were found between 63 septic shock blood samples and 337 normal whole blood samples. Then, we identified septic shock-specific 839 IRGs as the intersection of DEGs and IRGs. Moreover, we uncovered the regulatory networks based on co-expression analysis and found 28 co-expression interaction pairs. In the regulation network, protein phosphatase 3, catalytic subunit, alpha isozyme (PPP3CA) may regulate late estrogen response, glycolysis and TNFα signaling via NFκB and HLA; Kirsten rat sarcoma viral oncogene homolog (KRAS) may be related to late estrogen response and HLA; and Toll-like receptor 8 (TLR8) may be associated with TNFα signaling via NFκB. And the regulation mechanisms between TFs and IRGs (TLR8, PPP3CA, and KRAS) were validated by ChIP-seq and ATAC-seq. Conclusion: Our data identify three SSSIRGs (TLR8, PPP3CA, and KRAS) as candidate therapeutic targets for septic shock and provide constructed regulatory networks in septic shock to explore its potential mechanism.

Clinical Features of COVID-19 Patients With Venous Thromboembolism.

This study aimed to assess the clinical features of coronavirus disease 2019 (COVID-19) patients with VTE, to help develop preventive measures for venous thromboembolism (VTE in COVID-19) cases. COVID-19 patients admitted to Henan Provincial People's Hospital were retrospectively analyzed, including 23, 4 and 8 cases with mild to moderate, severe and critical symptoms, respectively. VTE incidence, age at onset, relevant laboratory parameters and prognosis were analyzed. Overall, VTE incidence in the 35 patients was 20.0%, occurring in severe (n = 1) and critical (n = 6) cases. D-dimer showed statistical significance in laboratory examination, representing except a diagnostic index and especial can be a prognostic factor in VTE among COVID-19 patients. Severe and critical COVID-19 cases had significantly reduced platelet counts, with a risk of hemorrhage. During treatment, the risk of both hemorrhage and thrombosis should be considered. VTE occurs in COVID-19 cases, affecting individuals with severe and critical symptoms. Significant D-dimer increase is of great significance in the risk assessment of death in critical cases of COVID-19. Appropriate measures should be taken to prevent VTE during treatment.

ß-Arrestin-2 attenuates hepatic ischemia-reperfusion injury by activating PI3K/Akt signaling.

Hepatic ischemia-reperfusion injury (IRI) remains a common complication during liver transplantation (LT), partial hepatectomy and hemorrhagic shock in patients. As a member of the G protein-coupled receptors adaptors, ARRB2 has been reported to be involved in a variety of physiological and pathological processes. However, whether ß-arrestin-2 affects the pathogenesis of hepatic IRI remains unknown. The goal of the present study was to determine whether ARRB2 protects against hepatic IR injury and elucidate the underlying mechanisms. To this end, 70% hepatic IR models were established in ARRB2 knockdown mice and wild-type littermates, with blood and liver samples collected at 1, 6 and 12 h after reperfusion to evaluate liver injury. The effect of ARBB2 on PI3K/Akt signaling during IR injury was evaluated in vivo, and PI3K/Akt pathway regulation by ARRB2 was further assessed in vitro. Our results showed that ARRB2 knockdown aggravates hepatic IR injury by promoting the apoptosis of hepatocytes and inhibiting their proliferation. In addition, ARRB2 deficiency inhibited PI3K/Akt pathway activation, while the administration of the PI3K/Akt inhibitor PX866 resulted in severe IR injury in mice. Furthermore, the liver-protecting effect of ARRB2 was shown to depend on PI3K/Akt pathway activation. In summary, our results suggest that ß-Arrestin-2 protects against hepatic IRI by activating PI3K/Akt signaling, which may provide a novel therapeutic strategy for treating liver ischemia-reperfusion injury.

Partial hepatectomy promotes implanted mouse hepatic tumor growth by activating hedgehog signaling.

OBJECTIVE: To investigate the role hedgehog signaling (Hh) in the growth of implanted hepatic tumors after partial hepatectomy (PH) in mice. METHODS: H22 cells were implanted to the scapula of 2 BALB/c (nu/nu) nude mice and tumor developed in 2 weeks. 40 nude mice were randomized into 4 groups: non-hepatectomy group (Sham operation group), 30% hepatectomy group, 70% hepatectomy group, and 70% hepatectomy with cyclopamine (Hh inhibitor). The hepatectomy model of nude mice was established. After hepatectomy, the tumor tissues incised from the scapula were implanted to the rest of the livers of the 4 groups. After 2 weeks, the tumor formation rates and the volumes of the implanted tumors were compared. Hh related proteins and downstream cytokine VEGF were tested by Western blot and Immunohistochemistry. All the data were analyzed to explore the role of Hh in the growth of tumor after PH. RESULTS: The volumes of the implanted tumors after liver resection were significantly higher in the 70% PH group than those in 0% and 30% PH groups; meanwhile, we also found that expression of the Hh ligand Indian Hh, its downstream transcription factor protein Gli-1, and its target VEGF were remarkably increased after PH, especially in the 70% PH group. Additionally, applying the Hh inhibitor cyclopamine to mice that underwent 70% PH significantly inhibited the growth of implanted tumors. CONCLUSIONS: The Hh signaling pathway was activated after PH and promoted liver regeneration. The growth of implanted hepatic tumors was also accelerated after PH via paracrine signaling.

Liver transplant may improve erectile function in patients with benign end-stage liver disease: single-center Chinese experience.

OBJECTIVES: No investigation in mainland China concerning erectile function in men with liver transplant for benign end-stage liver disease has been performed. MATERIALS AND METHODS: Sixty men with a liver transplant for benign end-stage liver disease (post-liver transplant group) between October 2003 and December 2008 were invited to evaluate erectile dysfunction with the Chinese version of the 5-item international index of erectile function. Fifty-seven patients with benign end-stage liver disease (pre-liver transplant group) on the waiting list also were investigated. RESULTS: The proportion of sexually active patients in the post-liver transplant group was higher than it was in the pre-liver transplant group (80% [48/60] vs 47.7% [21/44]; P < .01). The mean International Index of Erectile Function-5 score of responders was significantly higher in the post-liver transplant group than it was in the pre-liver transplant group (15.9 ± 8.5 vs 8.5 ± 9.1; P < .01). The incidences of no erectile dysfunction, mild, mild-moderate, moderate, and severe erectile dysfunction and total erectile dysfunction were 15.9% (7/44), 9.1% (4/44), 15.9% (7/44), 0% (0/44), 59.1% (26/44), and 84.1% (37/44) in the pre-liver transplant group, and 33.3% (20/60), 20% (12/60), 25% (15/60), 0 (0/60), 21.7% (13/60), and 66.7% (40/60) in the post-liver transplant group. The pre-liver transplant group had higher incidence of severe erectile dysfunction and total erectile dysfunction and a lower incidence of no erectile dysfunction than did the post-liver transplant group (P < .05). There was a comparable incidence of mild and mild-moderate erectile dysfunction with the post-liver transplant group (P > .05). Variables associated with International Index of Erectile Function-5 score of the post-liver transplant patients included age, profession, and immunosuppressive protocol. CONCLUSIONS: Liver transplant may improve erectile function in persons with benign end-stage liver disease, but erectile dysfunction remains a problem in the post-liver transplant patients.

[Reproduction after liver transplantation: a report of 13 cases from a single Chinese center].

OBJECTIVE: To explore the recipient's reproduction after liver transplantation (LT) and assess the outcomes of their offspring. METHODS: We retrospectively analyzed the reproduction status of 13 post-LT patients among 336 post-LT recipients during a follow-up period. Physical and intellectual status of their offspring were evaluated by developmental index and Denever developmental screening test. RESULTS: A total of 16 children were mothered or fathered by 13 LT patients. Two female patients mothered a boy and a girl. Ten male patients fathered 6 male and 8 female children while another male fathered a child at 28 gestational weeks. Eleven patients fathered the first gestation 21 mon (medium) since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean gestation age of (38.2 ± 1.8) weeks, with a mean birth weight of (3.1 ± 0.5) kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was found. Thirteen of 16 children had almost normal developmental indices and ten had almost normal Denever developmental screening. CONCLUSION: Post-LT patients of reproductive age are able to reproduce offspring. The short-term development of their offspring is relatively normal.

Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation.

BACKGROUND: The use of transanastomotic stents for Roux-en-Y hepatojejunostomy (RYHJ) in liver transplantation (LT) remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT. METHODS: RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents (S group), while 27 patients underwent the same procedure without transanastomotic stents (non-S group). The two groups were compared in terms of post-LT biliary complications and survival. RESULTS: The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5% (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0, 20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group. One and three year survival rates were 48.0% (12/25) and 34.0% (8/23), respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival (P > 0.05). CONCLUSION: The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT.

Health-related quality of life after liver transplantation: the experience from a single Chinese center.

BACKGROUND: Few studies have been performed to assess health-related quality of life (HRQOL) in liver transplantation (LT) patients in the mainland of China. This study aimed to investigate the HRQOL of post-LT patients in a single center. METHODS: HRQOL was evaluated by the SF-36 (Chinese version) questionnaire in 60 patients (LT group) who had received LT for benign end-stage liver disease (BELD). Fifty-five patients with BELD (BELD group) and 50 healthy volunteers from the general population (GP group) were also evaluated, and the results were compared among the three groups. RESULTS: There was a significant difference among the three groups in terms of the scores of eight domains in the SF-36 (P<0.01). Patients in the BELD group had lower scores in each domain of the SF-36 in comparison with those in the GP group (P<0.025). The LT group had mental health scores equivalent to those of the BELD group (P>0.025), but higher scores for the remaining seven domains (P<0.025). Compared with the GP group, the LT group scored equivalently for role physical, body pain, vitality, social function and role emotion (P>0.025), but had lower scores for the remaining three domains (P<0.025). Lower family income was found to be associated with reduced physical function and mental health scores (P<0.05). Better education was associated with increased mental health scores (P<0.05). CONCLUSIONS: LT patients generally have a good HRQOL although some respects of their HRQOL remains to be improved. Lower family income and poor education are important factors relating to the poor HRQOL of LT patients.

[Anxiety and depression for liver transplant recipients and their impact factors].

OBJECTIVE: To investigate the status of anxiety and depression for liver transplant (LT) recipients and explore their impact factors. METHODS: During the period of January 2005 to December 2008, the symptoms of anxiety and depression for 53 post-LT recipients (LT group) and 48 patients with benign end-stage liver disease (BELD group) were assessed by the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS). And they were compared with that of domestic norm (Norm group). The impact factors of anxiety and depression for LT recipients were analyzed by stepwise logistic regression. RESULTS: The anxiety scores of LT, BELD and Norm groups were (42 ± 9), (47 ± 11) and (30 ± 10) and the depression scores of three groups (48 ± 11), (52 ± 11) and (33 ± 9) respectively. The anxiety score was different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group (P < 0.01) while it was lower in the LT group than that in the BELD group (P < 0.05). The depression scores were different significantly among three groups (P < 0.01). It was higher in the LT and BELD groups than that in the Norm Group. And it was lower in the LT group than that in the BELD group (P < 0.05). The impact factor of anxiety for LT recipients was patient age and that of depression per capita monthly family income. CONCLUSION: The level of anxiety and depression of post-LT recipients is higher than that of domestic norm. The main impact factor for post-LT anxiety is patient age and that of depression per capita monthly family income.