Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Background: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. Methods: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. Results: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. Conclusion: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

[Retracted] MicroRNA­539 inhibits the proliferation and invasion of bladder cancer cells by regulating IGF­1R.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 2C on p. 4921 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at a different research institute. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a  reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 4917­4924, 2018; DOI: 10.3892/mmr.2018.8497].

Effect of preservation fluid contamination and associated possible donor-derived infections on early postoperative prognosis in kidney transplant recipients.

BACKGROUND: The study aims to analyze the epidemiology of preservation fluid (PF) contamination and investigate the impact of PF contamination and possible donor-derived infections(p-DDI) on early postoperative prognosis in kidney transplant (KT) recipients. METHODS: A total of 256 PF samples were collected for microbiological evaluation from all KT recipients who received deceased donor donations in our hospital from June 2018 to August 2022. Data on the baseline and clinical characteristics of these PF corresponding to recipients and donors were extracted from the electronic medical record. It mainly included the early postoperative complications and prognosis of KT recipients. RESULTS: From June 2018 to August 2022, 597 kidney transplants were performed in our center, with 260 recipients receiving kidney transplantation from donation after citizens' death. A total of 256 samples of PF were collected, of which 64.5% (165/256) were culture positive, and 24.6% (63/165) of the culture-positive PF were polymicrobial contamination. A total of 238 strains were isolated, of which coagulase-negative staphylococci (CoNS) had the highest proportion of 34.0% (81/238), followed by Klebsiella pneumoniae with 20.6% (49/238) and Escherichia coli with 8.8% (21/238). Recipients with culture-positive PF had a significantly higher incidence of postoperative infection (55.8% vs. 20.9%, P < 0.001) and DGF (38.2% vs. 24.2%, P = 0.023). In addition, the incidence of p-DDI was 12.9% (33/256). CRKP was the most common pathogen causing p-DDI. The recipients who developed p-DDI had a higher rate of graft loss (9.1% vs. 0.4%, P < 0.001), mortality (12.1% vs. 3.1%, P = 0.018), and longer postoperative hospital stay (30 days (19.5-73.5) vs. (22 days (18-32), P < 0.05) compared with recipients who did not develop p-DDI. CONCLUSIONS: Culture-positive PF is potentially significant for KT recipients, and p-DDI may increase the risk of poor prognosis for recipients. Prophylactic anti-infective treatment should be actively performed for highly virulent or multidrug-resistant (MDR) pathogens (especially Carbapenem-resistant Klebsiella pneumoniae, CRKP) in PF to avoid the occurrence of p-DDI.

Point-of-care detection of glycated hemoglobin using a novel dry chemistry-based electrochemiluminescence device.

As a good biomarker to reflect the average level of blood glucose, glycated hemoglobin (HbA1c) is mainly used for long-term glycemic monitoring and risk assessment of complications in diabetic patients. Previous analysis methods for HbA1c usually require complex pretreatment processes and large-scale biochemical analyzers, which makes it difficult to realize the point-of-care testing (POCT) of HbA1c. In this work, we have proposed a three-electrode dry chemistry-based electrochemiluminescence (ECL) biosensor and its self-contained automatic ECL analyzer. In this enzymatic biosensor, fructosyl amino-caid oxidase (FAOD) reacts with the hydrolysis product of HbA1c, and the produced hydrogen peroxide further reacts with luminol under the appropriate driving voltage, generating photons to realize the quantitative detection of HbA1c. Under optimized conditions, the biosensors have a good linear response to different concentrations of fructosyl valine (FV) ranging from 0.05 to 2 mM, with a limit of detection of 2 µM. The within-batch variation is less than 15%, and the biosensors still have 78% of the initial response after the accelerated aging test of 36 h at 37 °C. Furthermore, the recoveries for different concentrations of samples in whole blood were within 92.3-99.7%. These results illustrate that the proposed method has the potential for use in POCT of HbA1c.

A dry chemistry-based electrochemiluminescence device for point-of-care testing of alanine transaminase.

Liver disease causes serious public health problems because of its high prevalence, particularly affecting low- and middle-income countries. Alanine transaminase (ALT) is considered to be one of the most sensitive indicators for diagnosing liver disease. Although many strategies have been reported for ALT detection, few of them have solved the problem of automatic detection. In this work, for the first time, a dry chemistry-based electrochemiluminescence (DC-ECL) device is developed for point-of-care testing (POCT) of ALT, achieving real sample-to-answer detection. The proposed DC-ECL device consists of the following two components: (a) a DC-ECL chip consisting of the outer shell (including the top cap and pedestal) and detection layer (including the baseplate, electrode pad and carrier pad) and (b) an automatic ECL analyzer mainly including the data processing and instrument control unit, imaging detection unit, electrochemical reaction excitation unit, open detection window unit and rechargeable power supply. Under optimized conditions, the device had a wide detection range (0-1000 U/L), the ECL intensity linearly increased with ALT concentration (5-50 U/L) and logarithmic ALT concentration (50-1000 U/L), and the limit of detection was calculated to be 1.702 U/L. In addition, the DC-ECL device had the ability to measure ALT levels in human serum samples and showed acceptable selectivity, stability and repeatability. These results reveal that the DC-ECL device can overcome the disadvantages of traditional methods for ALT detection (such as high cost and requirement of professional technicians) and potentially opens the door to the development of similar POCT analyzers.

Effects of preservative fluid associated possible donor-derived carbapenem-resistant Klebsiella Pneumoniae infection on kidney transplantation recipients.

BACKGROUND: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study aimed to investigate the preservation fluid (PF) samples from deceased donors and report the impacts of possible donor-derived carbapenem-resistant Klebsiella pneumoniae (pdd-CRKP) infections on KT recipients. METHODS: A retrospective study was performed that included all recipients who received kidney transplantation from deceased donors in our hospital between December 2018 and December 2020. A total of 212 patients received kidney transplantation from deceased donors, a total of 206 PF samples were collected, and 20 recipients had a CRKP-positive culture. Both donors and recipients with CRKP-positive PF cultures were divided into two groups, and continuous variables between the two groups were compared using independent-sample t tests and Mann-Whitney tests. Categorical variables were compared using the chi-square test or Fisher's exact test. The significance level of p values was set at 0.05. RESULTS: A total of 337 recipients underwent kidney transplantation, including 212 recipients of organs from deceased donors and 110 corresponding deceased donors. A total of 206 PF samples were collected, and 20 recipients had CRKP-positive PF cultures. The donors' length of ICU stay was a potential risk factor for CRKP positivity in the PF culture (P < 0.05). Fifteen recipients were infected with pdd-CRKP, and the incidence of pdd-CRKP infection was 7.3% (15/206). The use of antibiotics, including ceftazidime-avibactam (CAZ-AVI), was a potential protective factor against death and graft loss in recipients with a CRKP-positive PF culture (P < 0.05). CONCLUSIONS: This study shows that the incidence of pdd-CRKP is high in our centre, recipients with pdd-CRKP infection can still achieve a good prognosis with the use of antimicrobial agents including CAZ-AVI.

A Statistical Prediction Model for Survival After Kidney Transplantation from Deceased Donors.

BACKGROUND In an environment of limited kidney donation resources, patient recovery and survival after kidney transplantation (KT) are highly important. We used pre-operative data of kidney recipients to build a statistical model for predicting survivability after kidney transplantation. MATERIAL AND METHODS A dataset was constructed from a pool of patients who received a first KT in our hospital. For allogeneic transplantation, all donated kidneys were collected from deceased donors. Logistic regression analysis was used to change continuous variables into dichotomous ones through the creation of appropriate cut-off values. A regression model based on the least absolute shrinkage and selection operator (LASSO) algorithm was used for dimensionality reduction, feature selection, and survivability prediction. We used receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis (DCA) to evaluate the performance and clinical impact of the proposed model. Finally, a 10-fold cross-validation scheme was implemented to verify the model robustness. RESULTS We identified 22 potential variables from which 30 features were selected as survivability predictors. The model established based on the LASSO regression algorithm had shown discrimination with an area under curve (AUC) value of 0.690 (95% confidence interval: 0.557-0.823) and good calibration result. DCA demonstrated clinical applicability of the prognostic model when the intervention progressed to the possibility threshold of 2%. An average AUC value of 0.691 was obtained on the validation data. CONCLUSIONS Our results suggest that the proposed model can predict the mortality risk for patients after kidney transplants and could help kidney specialists choose kidney recipients with better prognosis.

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation.

PURPOSE: The clinical efficacy of ceftazidime-avibactam (CAZ-AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP)-infected recipients after kidney transplantation (KT) has not been well evaluated. We aimed to assess its efficacy in a single-center cohort of KT recipients infected with CRKP. MATERIALS AND METHODS: We retrospectively observed KT recipients diagnosed with CRKP infection from June 2019 to July 2021. The primary outcome was 30-day mortality and secondary outcomes were 14-day clinical cure and 14-day microbiological cure. Logistic regression analysis was used to evaluate the relationship between CAZ-AVI treatment and prognosis. RESULTS: A total of 54 CRKP-infected KT recipients were recorded in this study. Twenty-two recipients received CAZ-AVI and 32 received other antibiotic regimens. Recipients in both groups had similar baseline characteristics, with the most common site of infection being surgical site infections (n=27; 50.0%) and bloodstream infections (n=23; 42.6%). Recipients treated with CAZ-AVI had significantly lower 30-day mortality (3/22 vs 14/32, P=0.019), significantly higher 14-day clinical cure (18/22 vs 17/32, P=0.030) and 14-day microbiological cure (19/22 vs 15/32, P=0.003) compared with recipients receiving other treatment regimens. Kaplan-Meier survival curves for 30-day mortality confirmed the findings (log-rank=0.014). In a multivariate logistic regression model, receiving CAZ-AVI was found to be an independent protective factor for 30-day mortality (odds ratio=0.148, 95% confidence interval, 0.027-0.800; P=0.026). No significant side effects were recorded. CONCLUSION: CAZ-AVI may be more valuable than other antibiotic regimens for the treatment of CRKP infection after kidney transplantation, and further large randomized controlled trials are needed to assess its efficacy.

Analysis of Risk Factors for Carbapenem-Resistant Klebsiella pneumoniae Infection and Its Effect on the Outcome of Early Infection After Kidney Transplantation.

Background: Infections remain a major cause of morbidity and mortality in kidney transplant (KT) recipients. This study was performed to identify the overall prevalence of early infections, prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after KT, one-year postoperative mortality in patients with early infections and risk factors for CRKP infections. Methods: We conducted a retrospective study of all patients who received KT in our hospital between January 2017 and December 2019. We evaluated the demographic, clinical, infection characteristics and the one-year postoperative outcomes. Results: Among the 419 patients who received KT between January 2017 and December 2019, 150 patients had at least one infection within 90 days after KT. The total prevalence of early infections was 36.1% (150/415), the prevalence of early CRKP infections was 10.4% (43/415), and the one-year postoperative mortality was 15.3% (23/150) in patients with early infections. The risk factors independently related to one-year postoperative mortality were mechanical ventilation (MV) > 48 h (Odds ratio (OR)= 13.879, 95%Confidence interval (CI): 2.265~85.035; P=0.004) and CRKP infection (OR=6.751, 95% CI: 1.051~43.369; P =0.044). MV> 48 h was independently related to CRKP infection (OR=3.719, 95% CI: 1.024~13.504; P=0.046). Kaplan-Meier survival curves showed that the one-year survival rate of patients infected with CRKP in the early postoperative stage was significantly lower than that of uninfected patients. Conclusions: In general, the prevalence of early infections after KT is high, and CRKP infection is closely correlated with poor prognosis. The effective prevention and treatment of CRKP infection is an important way to improve the one-year survival rate after KT.

MicroRNA­539 inhibits the proliferation and invasion of bladder cancer cells by regulating IGF­1R.

Bladder cancer is the most frequent malignancy of the urinary tract and the seventh most common cancer worldwide. The abnormal expression of microRNAs has been frequently observed in various types of human cancers, including bladder cancer. In addition, an increasing body of evidence has demonstrated that microRNAs are potential targets for cancer diagnosis, treatments and prognosis. The aim of the present study was to investigate the expression patterns and potential roles of microRNA­539 (miR­539) in bladder cancer and its underlying mechanism. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect miR­539 expression in the bladder cancer tissues and cell lines. Following transfection, MTT and cell invasion assays were used to investigate the effects of miR­539 overexpression or IGF1R underexpression on bladder cancer cell proliferation and invasion. Bioinformatics analysis, a luciferase reporter assay, RT­qPCR and western blot analysis were utilized to determine the potential targets of miR­539 in bladder cancer. The results revealed that miR­539 levels were relatively decreased in bladder cancer tissues and cell lines when compared with those observed in the matched adjacent normal bladder tissues and normal bladder epithelial cell line. miR­539 expression was associated with the tumor stage and lymph node metastasis of patients with bladder cancer. In addition, the expression of miR­539 suppressed bladder cancer cell proliferation and invasion. Insulin like growth factor 1 receptor (IGF­1R) was identified as a direct target of miR­539, and miR­539 was also observed to regulate the protein kinase B and extracellular signal­regulated kinases signaling pathways. IGF­1R was markedly upregulated in bladder cancer tissues and negatively associated with miR­539 expression levels. Furthermore, IGF­1R knockdown in bladder cancer cells significantly inhibited cell proliferation and invasion. To the best of our knowledge, these results demonstrated for the first time that miR­539 may act as a tumor suppressor and serve important roles in tumorigenesis and progression of bladder cancer. Thus, miR­539/IGF­1R may be a potential therapeutic target for the treatment of bladder cancer.