OBJECTIVE: To develop and validate a predictive model for the risk of bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). METHODS: A literature search was conducted in PubMed, Cochrane Library, and Embase databases from inception to July 2022 to identify studies reporting statistically significant risk factors for CRKP-BSI. Relative risks (RR) were extracted and pooled. Based on factor weights, a risk-scoring model was established. For external validation, hospitalized CRKP-infected patients from January 2016 to January 2022 at Shanghai First People's Hospital were included. Clinical data were used to calculate individual risk scores. The predictive accuracy was assessed using receiver operator characteristic curve (ROC curve). Patients were stratified into low-to-intermediate-risk and high-risk groups based on the optimal cut-off, and CRKP BSI incidence was compared between groups. RESULTS: The literatures related to the risk factors of CRKP-BSI published from database inception to July 2022 was retrieved and screened from PubMed, Cochrane Library, and Embase. Fourteen risk factors were included in the scoring model: cardiovascular disease, severe neutropenia or immunosuppression, intensive care unit (ICU) stay history, prior hospitalization, carbapenem exposure, aminoglycoside exposure, antifungal exposure, endotracheal intubation or tracheostomy, mechanical ventilation, hemodialysis, central venous catheter, indwelling urinary catheter, CRKP colonization, and Klebsiella pneumoniae positivity at non infection sites. The total score ranged from 0 to 173.5 points. In the validation cohort of 230 CRKP-infected patients, 41 developed CRKP BSI. The model yielded an area under the curve (AUC) of 0.783 (95%CI was 0.689-0.876). The optimal cut off was 81.25 points, with sensitivity of 75.6% and specificity of 81.0%. Based on this cut off, 163 patients were categorized as low-to-intermediate risk and 67 patients as high risk. The incidence of CRKP BSI in the high-risk group was significantly higher than in the low-to-intermediate-risk group [64.2% (43/67) vs. 4.9% (8/163); RR = 13.175 (95%CI was 5.920-29.319), P < 0.001]. CONCLUSIONS The model, based on 14 routinely available clinical parameters, demonstrated good performance in predicting CRKP BSI risk and may assist clinicians in early identification of high risk patients.
Humans ; Klebsiella pneumoniae/drug effects* ; Klebsiella Infections/microbiology* ; Carbapenems/pharmacology* ; Risk Factors ; Bacteremia/microbiology* ; ROC Curve ; Carbapenem-Resistant Enterobacteriaceae

OBJECTIVETo explore the genetic etiology of a patient with classic maple syrup urine disease (MSUD).

METHODSNext-generation sequencing (NGS) was used to screen the exons of BCKDHA, BCKDHB, DBT and DLD genes. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the protein structure and function.

RESULTSNGS and Sanger sequencing have detected a c.550delT mutation in exon 5 of the BCKDHB gene in the mother and a c.1046G>A mutation in exon 10 of the BCKDHB gene in the father, while no mutation was found with BCKDHA, DBT and DLD genes. Among these, the c.550delT is a novel mutation. Bioinformatic analysis suggested that the two mutations both located in a highly conserved region and may decrease the activity of branched-chain α-ketoacid dehydrogenase complex through alternation of its structure.

CONCLUSIONThe compound heterozygous mutations c.550delT and c.1046G>A of the BCKDHB gene probably underlie the clinical manifestations of the patient with classic MSUD.

Objective To study the therapeutic effect of rheum(Chinese herbal medicine) preparation made by using ultrasonic technique on pro-inflammatory cytokines and sepsis in rats.In order to offer novel measure for the treatment of critically ill patients.Methods Firstly, rheum sterile solution was prepared through ultrasonic technique.Secondly, fifty healthy male SD rats were randomly(random number) divided to CLP group and rheum group.Moderate degree of sepsis model was established by using cecal ligation and puncture(CLP).Rats in group rheum received the liquid rheumpreparation via intragastric administration, while rats in group CLP received saline instead.The 7-day survival rate was recorded and was compared between two groups.In addition, another fifty-four rats were randomly(random number) divided to sham group, CLP group and rheum group(n=18 in each group).CLP was performed to induce sepsis in CLP group and rheum group.Then rats in rheum group received rheum sterile solution via intragastric administration, while rats in CLP group received saline instead.At 12 hours, 24 hours and 48 hours after modeling, six rats in each group were randomly sacrificed.Serum TNF-α and HMGB1 levels were detected by ELISA method.Levels of RAGE, HMGB1 and NF-κB P65 in small intestine were detected by Western Blot.Results Level of anthraquinones extracted from rheum by ultrasonic technique was higher than that by conwentional decoction method.The 7-day survival rate of rats in rheum group(76%) was higher than that in CLP group(48%)(P<0.05).Compared with sham group, serum TNF-αand HMGB1 levels in CLP group and rheum group were significantly increased(P<0.05).TNF-α was significantly lower in rheum group than that in CLP group at each interval(P<0.05).At 12 hours after modeling, there was no significant difference in serum HMGB1 level between CLP group and rheum group(P>0.05).At 24 hours and 48 hours after modeling, serum HMGB1 levels were significantly lower in rheum group than those in CLP group(P<0.05).Compared with sham group, protein levels of HMGB1, RAGE and NF-κB in small intestine were elevated in CLP group and rheum group at 48 hours after modeling(P<0.01), while protein levels of above biomarker were higher in CLP group than those in rheum group(P<0.05).Conclusions Rheum sterile solution could down-regulate the level of pro-inflammatory cytokines, modulate the inflammatory response, and improve the survival rate in rats with sepsis.