Association of preoperative elevated lipoprotein (a) with poor survival in patients with biliary tract cancers.

BACKGROUND: Biliary tract cancers have garnered significant attention due to their highly malignant nature. The relationship between abnormal lipid metabolism and tumor occurrence and development is a research hotspot. However, its correlation with biliary tract cancers is unclear. METHODS: We enrolled 78 patients with biliary tract cancers and obtained data on clinical characteristics, pathological findings, and preoperative blood lipid indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipoprotein (a) [Lp(a)]. Receiver operating characteristic (ROC) curves were used to determine the optimal predictive cutoff values of lipid indicators among the participants. Independent risk factors were determined using Cox regression, and survival was predicted using the Kaplan-Meier method. Statistical analyses were performed using SPSS software. RESULTS: Univariate Cox regression analysis revealed that the body mass index (BMI), tumor location, surgical margin, N stage, and abnormally increased LDL-C, TG, and Lp(a) levels were significantly associated with poor prognosis of biliary tract cancers (p < 0.05). Multifactor Cox regression demonstrated that only N stage (HR = 3.393, p < 0.001) and abnormally increased Lp(a) levels (HR = 2.814, p = 0.004) were significantly associated with shorter survival. N stage and Lp(a) were identified as independent prognostic risk factors for patients with biliary tract cancers. CONCLUSION: This study presents Lp(a) as a novel biochemical marker that can guide clinical treatment strategies for patients with biliary tract cancers. More effective treatment options and intensive postoperative testing should be considered to prolong the survival of these patients with preoperative abnormal lipid metabolism.

The Value of Neutrophil-To-Lymphocyte Ratio for Evaluating Blood Stream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae: A Retrospective Cohort Study.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients. Methods: We performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders. Results: The overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076-1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322-11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017-0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047). Conclusions: The NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.

Emergence of Ceftazidime/Avibactam and Tigecycline Resistance in Carbapenem-Resistant Klebsiella pneumoniae Due to In-Host Microevolution.

Klebsiella pneumoniae can cause both hospital- and community-acquired clinical infections. Last-line antibiotics against carbapenem-resistant K. pneumoniae (CRKP), such as ceftazidime/avibactam (CZA) and tigecycline (TGC), remain limited as treatment choices. This study aimed to investigate the mechanisms by which CRKP acquires CZA and TGC resistance in vivo under ß-lactam antibiotic and TGC exposure. Three CRKP strains (XDX16, XDX31 and XDX51) were consecutively isolated from an inpatient with a urinary tract infection in two months. PFGE and MLST showed that these strains were closely related and belonged to sequence type (ST) 4496, which is a novel ST closely related to ST11. Compared to XDX16 and XDX31, XDX51 developed CZA and TGC resistance. Sequencing showed that double copies of blaKPC-2 were located on a 108 kb IncFII plasmid, increasing blaKPC-2 expression in XDX51. In addition, ramR was interrupted by Insertion sequence (IS) Kpn14 in XDX51, with this strain exhibiting upregulation of ramA, acrA and acrB expression compared with XDX16 and XDX31. Furthermore, LPS analysis suggested that the O-antigen in XDX51 was defective due to ISKpn26 insertion in the rhamnosyl transferase gene wbbL, which slightly reduced TGC susceptibility. In brief, CZA resistance was caused mainly by blaKPC-2 duplication, and TGC resistance was caused by ramR inactivation with additional LPS changes due to IS element insertion in wbbL. Notably, CRKP developed TGC and CZA resistance within one month under TGC and ß-lactam treatment without exposure to CZA. The CRKP clone ST4496 has the ability to evolve CZA and TGC resistance rapidly, posing a potential threat to inpatients during antibiotic treatment.

The Emergence of Novel Sequence Type Strains Reveals an Evolutionary Process of Intraspecies Clone Shifting in ICU-Spreading Carbapenem-Resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent public health problem worldwide, and its rapid evolution in the clinical environment has been a major concern. A total of 99 CRKP isolates spreading in the intensive care unit (ICU) setting were included and subjected to whole-genome sequencing, and their sequence types (STs), serotype loci, and virulence determinants were screened based on genome data. The phylogenetic structure was reconstructed based on the core genome multilocus sequence typing method. Regions of recombination were assessed. Biofilm formation, serum resistance assays, and a Galleria mellonella infection model were used to evaluate strain virulence. A novel ST, designated ST4496, emerged in the ICU and spread for 6 months before its disappearance. ST4496 was closely related to ST11, with only a single-allele variant, and ST11 is the most dominant clinical clone in China. Recombination events occurred at capsule biosynthesis loci and divided the strains of ST11 and its derivative ST4496 into three clusters, including ST11-KL47, ST11-KL64, and ST4496-KL47. The phylogenetic structure indicated that ST11-KL47 was probably the origin of ST11-related strain evolution and presented more diversity in terms of both sequence similarity and phenotypes. ST4496-KL47 cluster strains presented less virulence than ST11-KL64, which was probably one of the factors preventing the former from spreading widely. In conclusion, ST4496-KL47 was probably derived from ST11-KL47 via intraspecies shifting but was less competitive than ST11-KL64, which also evolved from ST11-KL47 and developed increased virulence via capsule biosynthesis locus recombination. ST11-KL64 has the potential to be the predominant CRKP clone in China.

Metabolite release and rheological properties of sponge cake after in vitro digestion and the influence of a flour replacer rich in dietary fibre.

The present study aimed to better understand the metabolite release and rheological characteristics of sponge cake after in vitro digestion and the effect of Eucheuma as a fibre-rich flour replacer. Overall, 22 compounds including amino acids, saccharides, fatty acids, and other metabolites were identified based on nuclear magnetic resonance spectra. Principal component analysis and orthogonal projection to latent structures-discriminant analysis showed that Eucheuma reduced the release of amino acids and fatty acids. The released glucose from the EP20 sample (20% replacement of flour with Eucheuma) decreased by 35.4% in intestinal phases compared with the control cake. Eucheuma's in vitro effects on sponge cake digestion mainly reflected altered flow behaviour index. All samples showed solid-like behaviour and a decrease in viscoelastic moduli after digestion. This study forms the basis for future optimisation of food properties to control their digestive characteristics.

Xylitol and Maltitol Improve the Rheological Property of Kappa-Carrageenan.

To further extend the use of κ-carrageenan (κ-C) in real food systems (such as beverages), the understanding of gelation properties of κ-C with the presence of food ingredients is critical. The effects of xylitol and maltitol (up to 30 wt %) on the rheological and structural properties of κ-C were inspected by means of rheometer and Fourier transform infrared (FTIR). With the addition of xylitol, the gelation temperature increased from 44.1 to 57.3 °C, while the gelation temperature increased from 44.1 to 61.4 °C in maltitol systems. With the increasing concentration of both xylitol and maltitol, the values of fractal dimension df and complex modulus G* of κ-C increased, while the relaxation exponent n decreased from 0.87 to 0.39 of xylitol and 0.87 to 0.78 of maltitol, respectively. These indicated that the gel networks of aqueous κ-C were improved by the addition of xylitol and maltitol. The FTIR results showed that the interaction between κ-C and these polyols contributed to the increase of hydrogen bonds. The effects of maltitol on κ-C were stronger than those of xylitol because of more equatorial-OH bonds in maltitol. These findings contribute to a better understanding of the gelation processes of κ-C/polyols systems.

Effect of ramR loss-of-function insertion on tigecycline resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Tigecycline is an antibacterial agent restricted for use against carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to identify the tigecycline resistance mechanism in clinical CRKP isolates obtained from a 60-year-old femalepatient during tigecycline treatment. METHODS: Three K. pneumoniae isolates obtained during tigecycline treatment were subjected to antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, and whole-genome sequencing and analysis. The function of ramR was confirmed by gene complementation. RESULTS: Three K. pneumoniae isolates (W814, W112 and W113) were collected from the patient on Days 0, 10 and 13, respectively, of ongoing tigecycline treatment. Antimicrobial susceptibility testing showed resistance to all antibiotics except tigecycline and ceftazidime/avibactam. The tigecycline minimum inhibitory concentration (MIC) for strains W814 and W112 was 4 mg/L compared with 16 mg/L for strain W113. The three strains belonged to sequence type 11 (ST11) and had a similar PGFE pattern. Insertion sequence (IS) element ISKpn18 in ramR was identified in strain W113. A parent strain transformed with plasmid pCR2.1-Hyg carrying ramR enhanced tigecycline susceptibility, thus confirming that a loss-of-function insertion in ramR contributes to tigecycline resistance. CONCLUSION: ISKpn18 insertion in the ramR gene contributes to the tigecycline resistance mechanism in the isolated K. pneumoniae strains.