Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome

Background and aims There has been no reliable severity system based on the prognosis to guide therapeutic strategies for patients with pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). We aimed to create a novel Drum Tower Severity Scoring (DTSS) system for these patients to guide therapy. Methods 172 Patients with PA-HSOS who received supportive care and anticoagulation therapy in Nanjing Drum Tower Hospital from January 2008 to December 2020 were enrolled and analyzed retrospectively. These patients were randomized into a training or validation set in a 3:1 ratio. Next, we established and validated the newly developed DTSS system. Results Analysis identified a predictive formula: logit (P) = 0.004 × aspartate aminotransferase (AST, U/L) + 0.019 × total bilirubin (TB, μmol/L) − 0.571 × fibrinogen (FIB, g/L) − 0.093 × peak portal vein velocity (PVV, cm/s) + 1.122. Next, we quantified the above variables to establish the DTSS system. For the training set, the area under the ROC curve (AUC) (n = 127) was 0.787 [95% confidence interval (CI) 0.706–0.868; p < 0.001]. With a lower cut-off value of 6.5, the sensitivity and negative predictive value for predicting no response to supportive care and anticoagulation therapy were 94.7% and 88.0%, respectively. When applying a high cut-off value of 10.5, the specificity was 92.9% and the positive predictive value was 78.3%. For the validation set, the system performed stable with an AUC of 0.808. Conclusions The DTSS system can predict the outcome of supportive care and anticoagulation in PA-HSOS patients with satisfactory accuracy by evaluating severity, and may have potential significance for guiding therapy.

940 Targeting DKK1 to reverse immunosuppressive macrophages and enhance PD-1 blockade therapy in gastric cancer

BackgroundGastric cancer (GC) is a highly heterogeneous and immunosuppressive cancer type with poor prognosis. Current immunotherapies like immune checkpoint blockade (ICB) have very modest therapeutic effect in GC patients, reflecting urgent need for exploring new immunotherapeutic targets.MethodsIHC and mRNA analysis of 384 patients from Drum Tower Hospital Cohort and 1192 patients from other databases were performed to investigate Dickkopf-1 (DKK1) expression and local immune status. The MFC-challenged subcutaneous and abdominal dissemination GC models were established, and the impact of DKK1 blockade on gastric tumor immune microenvironment (TIME) and anti-tumor responses was explored by flow cytometry and RNA sequencing. In vivo immune cell-depletion GC models were constructed to further assess the function of DKK1 on different immune cell types. RAW264.7 and mouse bone marrow derived macrophages (BMDMs) were employed to analyze DKK1 modulation on macrophages in vitro by Cytometric Bead Array, flow cytometry and western bolt.ResultsIn present study, we found high DKK1 expression is associated with poor overall survival and worse immune status in GC patients. DKK1 blockade could improve gastric TIME, including increased accumulation and activation of CD8+ T cells and NK cells, and trigger an effective anti-tumor response both in subcutaneous and abdominal dissemination GC models. DKK1 directly induces macrophages towards an immunosuppressive phenotype, while the TIME improvement and tumor reduction depend on the reversion of immunosuppressive macrophages mediated by DKK1 blockade. Furthermore, combined inhibition of PD-1 and DKK1 could achieve superior anti-tumor effect on GC models.ConclusionsThus, our work identifies a new role of DKK1 to induce immunosuppressive TIME through macrophage modulation, and reveals DKK1 to be a novel and promising immunotherapeutic target for GC.Ethics ApprovalThe collection and analysis of tumor tissue sections were approved by the Ethics Committee of Nanjing University Medical School Affiliated Drum Tower Hospital (2021-324-01). All animal experiments were approved by the Institutional Animal Care and Use Committee of Drum Tower Hospital (approval number: 2020AE01064).

Analysis On The Association of Intraoperative Fluid Balance and Short-Term Outcomes After Radical Gastrectomy in Aged Patients

Background: To observe the relationship between fluid balance and the short-term outcomes of aged patients after gastrectomy for gastric cancer in Nanjing Drum Tower Hospital.Methods: The clinical data of patients with gastrectomy for gastric cancer from January 2016 to December 2018 in Nanjing Drum Tower Hospital were retrospectively analyzed. According to the criteria of inclusion and exclusion, 691 patients who met the study conditions were analyzed according to intraoperative fluid balance recorded on patients who has undergone radical gastrectomy. Patients were classified into three fluid administration groups representing incremental quartiles of the primary exposure variable. Preoperative characteristics used for statistical adjustment included gender, age, weight, admission type, ASA degree. Operative factors included procedure duration, estimated blood loss, urine output, and so on. The primary outcomes included acute kidney injury (AKI).and postoperative respiratory complications (PRCs) Exploratory outcomes included length of stay, postoperative length of stay and total cost of hospitalization. The association between perioperative factors and AKI/PRCs in hospital was tested with multivariable logistic regression analyses.Results: 16 cases were diagnosed as AKI and 23 cases were diagnosed as PRCs. The association between intraoperative fluid balance and the incidence of acute kidney injury (AKI)/postoperative respiratory complications (PRCs) remained U-shaped but the difference was not statistically significant (P>0.05). After adjustment for potential confounders, lower urine output (P=0.017, OR=0.997,95%CI=0.994-0.999) and coronary heart disease (P=0.032, OR=4.867,95%CI=1.142-20.75) were independent predictor of AKI in aged patients after radical gastrectomy. Besides, coronary heart disease(OR=3.371,95%CI=1.021-11.129,P=0.049) and intestinal obstruction (OR=12.501,95%CI=3.058-51.107,P ＜0.0005) were independent predictor of PRCs in aged patients after radical gastrectomy.Conclusion: There were no significant association between the incidence of AKI or any other complications and intraoperative fluid balance during radical gastrectomy in aged patients. Lower urine output and coronary heart disease were independent predictors of AKI in aged patients after radical gastrectomy. Coronary heart disease and intestinal obstruction were independent predictors of PRCs in aged patients after radical gastrectomy.Trial registration: This study was approved by the Affiliated Drum Tower Hospital of Nanjing University (Registration number: 2018-162-01).

Application of Endoport-Assisted Neuroendoscopic Techniques in Lateral Ventricular Tumor Surgery

PurposeThe aim of this study was to review the experience of Endoport-assisted neuroendoscopic surgery for lateral ventricular tumors resection, investigate the therapeutic efficiency and discuss the key points. MethodsWe retrospectively reviewed the clinical data of 16 patients suffering from lateral ventricular tumors. All the patients received Endoport-assisted neuroendoscopic surgery from January 2018 to June 2020 in the department of neurosurgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. ResultsAll the patients received standardized treatment according to the preoperative image data and the postoperative pathology of the tumors. Endoport-assisted Neuroendoscopic surgery achieved complete removal of lateral ventricular tumors in 14 cases (87.5%) and subtotal removal in 2 cases (12.5%, glioma). The perioperative complications were analyzed, 1 acute epidural hematoma occurred during surgery, 1 hemiplegia and 2 obstructive hydrocephalus occurred after surgery. All the complications were managed timely. During the long-time follow up, the patient with glioblastoma died 16 months after surgery, the other patients are still alive with Glasgow outcome scales not less than 4.ConclusionEndoport-assisted neuroendoscopic surgery is suitable for the resection of lateral ventricular tumors. This procedure is simple, effective, minimally invasive, and associated with fast postoperative recovery.

Identify the Early Predictor of Mortality in Patients with Acute Paraquat Poisoning

Background. Paraquat is a widely used nonselective and fast-acting contact herbicide worldwide. This study identified the early predictor of mortality in patients with acute paraquat poisoning. Methods. Twenty-nine patients with acute paraquat poisoning admitted at Nanjing Drum Tower Hospital from January 2018 to August 2020 were included in this study. The early predictor of mortality in patients with acute paraquat poisoning based on the blood tests was identified by correlation, logistic regression, and receiver operating characteristic (ROC) analyses. Result. 15 of the 29 patients died after poisoning. Compared to the survivors, the neutrophilic granulocyte ratio, leukocyte count, ALB, and Crea of the nonsurvivors were significantly higher with p value < 0.05, while the lymphocyte ratio and eGFR(MDRD) of the nonsurvivors were remarkably lower with p value < 0.01. Moreover, the neutrophil-to-lymphocyte ratio (NLR) was remarkably upregulated in the nonsurvivors. The area under the ROC curve (AUC) of the neutrophilic granulocyte ratio, lymphocyte ratio, leukocyte count, ALB, Crea, eGFR(MDRD), and NLR to predict the mortality in patients with acute paraquat poisoning was 0.8905 (95% CI: 0.7589-1.022), 0.8643 (95% CI: 0.7244-1.004), 0.8500 (95% CI: 0.7133-0.9867), 0.7286 (95% CI: 0.5338-0.9233), 0.8167 (95% CI: 0.6620-0.9713), 0.8714 (95% CI: 0.7330-1.010), and 0.8667 (95% CI: 0.7277-1.006), respectively. More interestingly, we also evaluated the diagnostic values of the different combinations of six blood test biomarkers by logistic regression analysis. According to the results of the logistic regression analysis, the AUCs for the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) were the largest with 0.986 (95% CI: 0.952-1), and the sensitivity and specificity were 100% and 100%. Conclusion. This study demonstrated that the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) could serve as an ideal early predictor of mortality in patients with acute paraquat poisoning. However, further research is needed to draw a clear conclusion.

Genomic characterization of carbapenem resistant Escherichia coli from multiple hospitals in Nanjing, China: focusing on frequent co-occurrence of blaNDM and blaKPC-2

Background: The increasing emergence of carbapenem resistant Escherichia coli (CREC) poses a potential threat to public health, hence genomic characterization of isolates is needed for a better understanding of its transmission and implementation of infection control measures. Materials and methods：Eleven CREC isolates were collected in 2015 from 6 hospitals in Nanjing, China, and analyzed using whole genome sequencing. Resistance determinants, virulence elements, multi-locus sequence type (MLST), serotypes, phylogeny and fimH types were determined. Results: All of the CREC carried at least one carbapenemase. NDM-5 (n=9) was the most frequent carbapenemase, followed by KPC-2 (n=3) and NDM-1 (n=2); three isolates produced NDM-5 and KPC-2. Ten out of the 11 isolates co-carried blaCTX-M variants. MLST analysis found 7 distinct STs, including ST410 (n=2), ST3489 (n=1), ST156 (n=1), ST683 (n=1), ST297 (n=1), ST167 (n=1), and ST361 (n=1). Six distinct serotypes and 8 Fim types were identified. A great diversity of plasmid profiles was observed with plasmid replicon IncX3 being the most frequent (n=11). Phylogenetic analysis showed great diversity between the 11 CREC isolates and also between 6 additional isolates co-carrying blaNDM and blaKPC which were selected from the strains collection of Nanjing Drum Tower Hospital for comparison. Conjugation assays demonstrated that blaNDM was transferable. Conclusion: NDM is the major carbapenemase among CREC, with NDM-5 being the main variant which can be horizontally disseminated by IncX3 plasmids. These isolates displayed genetic diversity by MLST, Fim typing and serotyping. We herein provided the first report on emergence of NDM-5 producing E. coli ST297, ST683, ST3489, and NDM-1 producing E. coli ST361.

Clinical diagnosis and treatment of throat foreign bodies under video laryngoscopy

Objective This study was designed to explore the clinical application of video laryngoscopy in the diagnosis and treatment of throat foreign bodies (FBs). Method In total, 1572 patients diagnosed with throat FBs at the Department of Otolaryngology of Nanjing Drum Tower Hospital were retrospectively analysed. The covariables collected were the time from FB ingestion to admission, age, sex, duration of admission, and site of impaction. Result The most common FBs were fish bones, which accounted for 1446 (91.98%) of 1572 FBs. Among all 1572 FBs, 1004 (63.87%) were successfully removed by video laryngoscopy without complications. A shorter duration of admission was associated with a higher diagnostic rate under video laryngoscopy. The diagnostic rate of sharp FBs was significantly higher than that of non-sharp FBs. The most common sites of throat FBs were the tongue root (42.29%), epiglottic vallecula (19.40%), tonsil (18.21%), and piriform fossa (10.65%). Conclusion Video laryngoscopy is a powerful tool for the diagnosis and treatment of throat FBs, allowing for identification of rare locations of FBs as well as refractory FBs.

Genomic characterization of carbapenem resistant Escherichia coli from multiple hospitals in Nanjing, China: focusing on frequent co-occurrence of blaNDM and blaKPC-2

Background The increasing emergence of carbapenem resistant Escherichia coli (CREC) poses a potential threat to public health, hence genomic characterization of isolates is needed for a better understanding of its transmission and implementation of infection control measures. Materials and methods Eleven CREC isolates were collected in 2015 from 6 hospitals in Nanjing, China, and analyzed using whole genome sequencing. Resistance determinants, virulence elements, multi-locus sequence type (MLST), serotypes, phylogeny and fimH types were determined. Results All of the CREC carried at least one carbapenemase. NDM-5 (n = 9) was the most frequent carbapenemase, followed by KPC-2 (n = 3) and NDM-1 (n = 2); three isolates produced NDM-5 and KPC-2. Ten out of the 11 isolates co-carried blaCTX-M variants. MLST analysis found 7 distinct STs, including ST410 (n = 2), ST3489 (n = 1), ST156 (n = 1), ST683 (n = 1), ST297 (n = 1), ST167 (n = 1), and ST361 (n = 1). Six distinct serotypes and 8 Fim types were identified. A great diversity of plasmid profiles was observed with plasmid replicon IncX3 being the most frequent (n = 11). Phylogenetic analysis showed great diversity between the 11 CREC isolates and also between 6 additional isolates co-carrying blaNDM and blaKPC which were selected from the strains collection of Nanjing Drum Tower Hospital for comparison. Conjugation assays demonstrated that blaNDM was transferable. Conclusion NDM is the major carbapenemase among CREC, with NDM-5 being the main variant which can be horizontally disseminated by IncX3 plasmids. These isolates displayed genetic diversity by MLST, Fim typing and serotyping. We herein provided the first report on emergence of NDM-5 producing E. coli ST297, ST683, ST3489, and NDM-1 producing E. coli ST361.