Efficacy of Zidovudine-Amikacin Combination Therapy In Vitro and in a Rat Tissue Cage Infection Model against Amikacin-Resistant, Multidrug-Resistant Enterobacteriales.

Multidrug-resistant (MDR) Enterobacteriales infections have become an urgent global threat to public health. The aim of this study was to evaluate the efficacy of zidovudine-amikacin combination therapy in vitro and in vivo. Molecular characteristics and antibiotic resistance profiles of 53 amikacin-resistant MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR) clinical isolates were examined via PCR and susceptibility testing. Checkerboard assays were performed for these 53 isolates to assess in vitro synergistic effects of the zidovudine-amikacin combination, and static time-kill experiments were performed for four XDR or PDR Enterobacteriales isolates. A Galleria mellonella model and a rat tissue cage infection model were established to assess in vivo synergistic effects. The aac(6')-Ib gene was detected in 25 (47.2%) isolates, followed by armA in 5 (9.4%) isolates, rmtB in 27 (50.9%) isolates, and rmtC in 3 (5.8%) isolates. Checkerboard assays showed the synergy of this combination against 38 (71.7%) isolates. The time-kill assays further confirmed that zidovudine strongly synergized with amikacin against four XDR or PDR Enterobacteriales isolates. The Galleria mellonella model study showed that the survival benefit of zidovudine-amikacin combination therapy was significantly better than that of monotherapy for those four Enterobacteriales isolates. Furthermore, the rat tissue cage infection model study showed that zidovudine-amikacin combination therapy displayed more potent bactericidal activity than monotherapy after 3 and 7 days of treatment for the above four isolates. Our data support the idea that the zidovudine-amikacin combination could be a plausible alternative therapy against infections with amikacin-resistant MDR Enterobacteriales, especially with XDR and PDR Enterobacteriales. IMPORTANCE Our study revealed for the first time that the zidovudine-amikacin combination shows a significant bactericidal effect against amikacin-resistant MDR, XDR, and PDR Enterobacteriales. Second, using in vitro and in vivo approaches, our study showed that zidovudine strongly synergized with amikacin against amikacin-resistant MDR Enterobacteriales isolates. Most importantly, with regard to survival benefit, pharmacokinetics, and bactericidal effects, our in vivo experiment demonstrated the effectiveness of zidovudine-amikacin.

[Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/ß-catenin/PPARγ pathway in arrhythmic rats].

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/ß-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/ß-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and ß-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and ß-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/ß-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.

Association between delta anion gap and hospital mortality for patients in cardiothoracic surgery recovery unit: a retrospective cohort study.

BACKGROUNDS: High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax - AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). METHODS: In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid-base variables. Cox regression model and Kaplan Meier curve were applied to predict patients' 90-day overall survival (OS). RESULTS: A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11-1.39, p < 0.001). The area under curve (AUC) values of ΔAG suggested a good diagnostic accuracy (AUC = 0.769). We established the following formula to estimate patients' hospital mortality: Logit(P) = - 15.69 + 0.21ΔAG + 0.13age-0.21BE + 2.69AKF. After calculating Youden index, patients with ΔAG ≥ 7 was considered at high risk (OR = 4.23, 95% CI: 1.22-14.63, p = 0.023). Kaplan Meier curve demonstrated that patients with ΔAG ≥ 7 had a poorer 90-day OS (Adjusted HR = 3.20, 95% CI: 1.81-5.65, p < 0.001). CONCLUSION: ΔAG is a prognostic factor of hospital mortality and 90-day OS. More prospective studies are needed to verify and update our findings.

Surgical Apgar score could predict complications after esophagectomy: a systematic review and meta-analysis.

OBJECTIVES: Esophagectomy is the most effective treatment for oesophageal cancer, although the incidence of postoperative complications remains high. Severe major complications, such as intrathoracic anastomotic leakage, are costly and life-threatening to patients. Therefore, early identification of postoperative complications is essential. The surgical Apgar score (SAS) was introduced by Gawande and colleagues to predict major complications after oesophagectomy. Several studies were carried out with inconsistent results. METHODS: PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library were searched for studies regarding SAS and oesophagectomy. Forest plots were generated using a random-effects model to investigate the actual predictive value of SAS in identifying major complications after oesophagectomy. RESULTS: Nine retrospective cohort studies were finally identified from selected electronic databases. The meta-analysis demonstrated that SAS could forecast the incidence of postoperative complications (odds ratio = 1.82, 95% confidence interval: 1.43-2.33, P < 0.001). Subgroup analysis validated the predictive value of SAS whether as continuous or discrete variables. In addition, a meta-analysis of 4 studies demonstrated that SAS could predict the incidence of pulmonary complications (odds ratio = 2.32, 95% confidence interval: 1.61-3.36, P < 0.001). Significant heterogeneity but no publication bias was found. CONCLUSIONS: Lower SAS scores could predict the incidence of major morbidities and pulmonary complications after oesophagectomy. Significant heterogeneity limits the reliability of the results, even if publication bias is not observed. More high-quality prospective research should be conducted to verify the findings. PROSPERO registration ID: CRD42020209004.

Distinguishing optimal esophagectomy candidates in elderly patients: A nomogram based on propensity score matching.

BACKGROUND: A survival benefit from esophagectomy was observed in elderly patients. But it's unclear how to identify specific patients who can benefit. Thus, we aimed to establish a predictive model to identify optimal candidates for esophagectomy. METHODS: Patients (age ≥75 years) with esophageal cancer in Surveillance, Epidemiology and End Results (SEER) database were used to establish the predictive model. Propensity-score matching (PSM) was applied to eliminate the imbalance between esophagectomy group and non-esophagectomy group. We hypothesized that elderly patients could benefit from esophagectomy with longer cancer specific survival (CSS) time than those who did not receive esophagectomy. Patients received surgery were divided into beneficial group and non-beneficial group according to the median CSS time of non-esophagectomy group. Prognostic factors affecting patients' long-term survival were identified. Among esophagectomy group, a logistic regression model based on these factors was established to build a nomogram. RESULTS: A total of 7,025 eligible patients were extracted from the SEER database, with 831 patients received esophagectomy. Surgery was independently associated with better long-term survival (median CSS time in the matched population: 35 vs. 8 months, p < 0.001). As a result, 361 (68.6%) patients were divided into beneficial group (CSS >8 months). Factors including age, tumor site, histology, differentiation grade, TNM stage, and tumor size were used to formulate the nomogram, which was named as esophagectomy candidates screening score (ECSS). The validation from two aspects showed the model a useful and stable one. CONCLUSION: A predictive model was established to distinguish optimal candidates for esophagectomy among elderly patients with EC.

Predictive value of postoperative C-reactive protein-to-albumin ratio in anastomotic leakage after esophagectomy.

INTRODUCTION: Among the many possible postoperative complications, anastomotic leakage (AL) is the most common and serious. Therefore, the purpose of this study was to explore the ability of various inflammatory and nutritional markers to predict postoperative AL in patients after esophagectomy. METHODS: A total of 273 patients were retrospectively evaluated and enrolled into this study. Perioperative, surgery-related, tumor-related and laboratory tests data were extracted and analyzed. The discriminatory ability and optimal cut-off value was evaluated according to the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were performed to access the potential risk factors for AL. RESULTS: The overall incidence of AL was 12.5% (34/273). C-reactive protein-to-albumin ratio (CRP/ALB ratio) [AUC 0.943 (95% confidence interval (CI) = 0.911-0.976, p <  0.001)] and operation time [AUC 0.747 (95% CI = 0.679-0.815, p <  0.001)] had the greatest discrimination on AL prediction. Multivariate analysis demonstrated that CRP/ALB ratio and operation time were two independent risk factors for AL, and CRP/ALB ratio (OR = 102.909, p <  0.001) had an advantage over operation time (OR = 9.363, p = 0.020; Table 3). CONCLUSION: Operation time and postoperative CRP/ALB ratio were two independent predictive indexes for AL. Postoperative CRP/ALB ratio greater than 3.00 indicated a high risk of AL. For patients with abnormal postoperative CRP/ALB ratio, early non-operative treatment or surgical intervention are needed to reduce the serious sequelae of AL.

The ratio of gastric tube length to thorax length: a vital factor affecting leak after esophageal cervical anastomosis.

BACKGROUND: Esophagogastric anastomotic leak (AL) is a severe complication following esophageal resection. This study aims to explore preliminarily whether the ratio of the gastric conduit length to the thorax length can be regarded as a potential prognostic variable for AL, and if so, a cut-off value can be found to divide the patients into distinct risk groups. METHODS: We retrospectively reviewed the clinical data of 273 patients who underwent esophagectomy. The gastric conduit length, the thorax length, and other covariates were collected. Logistic regression was first conducted to probe the rationality of the ratio as a risk indicator of AL. Then the dichotomizing analysis was applied to find the optimal cut-off value. RESULTS: The incidence of AL was 12.5% (34/273). The coefficient of the ratio in the logistic regression equation was -7.901 with P<0.001, which indicated that the larger the ratio, the smaller the risk of AL. Further smoothed scatter plots revealed that a potential step function of the ratio of AL incidence exists, of which the steep part ranges from 1.74 to 1.90. Results of the accurate cut-off value search through a minimum P value approach give the optimal dichotomization point of 1.79. CONCLUSIONS: The ratio of the gastric conduit length to the thorax length can reflect the tension in the anastomosis. The research proposes that surgeons can control the length of the gastric conduit during reconstruction to reduce the tension in the anastomosis and thus lead to a decrease in the incidence of AL.

The prognostic value of modified NUTRIC score for patients in cardiothoracic surgery recovery unit: A retrospective cohort study.

BACKGROUND: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. METHODS: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. RESULTS: The optimal cut-off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32-4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan-Meier curve indicated that patients at high nutritional risk have poorer 365-days [hazard ratio (HR) = 1.76, 95% CI = 1.30-2.37, p < 0.001] and 1000-days (HR = 2.30, 95% CI = 1.87-2.83, p < 0.001) overall survival. CONCLUSIONS: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long-term survival in CSRU patients. More well-designed clinical trials are needed to verify and update our findings.

Comparison of short-term clinical outcomes between robot-assisted minimally invasive esophagectomy and video-assisted minimally invasive esophagectomy: a systematic review and meta-analysis.

BACKGROUND: Though robot-assisted minimally invasive esophagectomy (RAMIE) is demonstrated to offer a better visualization and provide a fine dissection of the mediastinal structures to facilitate the complex thoracoscopic operation, the superiorities of RAMIE over MIE have not been well verified. The aim of this study was to explore the actual superiorities through comparing short-term results of RAMIE with that of MIE. METHODS: PubMed, EMBASE and web of science databases were systematically searched up to September 1, 2020 for case-controlled studies that compared RAMIE with TLMIE. RESULTS: Fourteen studies were identified, with a total of 2,887 patients diagnosed with esophageal cancer, including 1,435 patients subjected to RAMIE group and 1,452 patients subjected to MIE group. The operative time in RAMIE was still significantly longer than that in MIE group (OR =0.785; 95% CI, 0.618-0.952; P<0.001). The incidence of pneumonia was significantly lower in RAMIE group compared with MIE group (OR =0.677; 95% CI, 0.468-0.979; P=0.038). CONCLUSIONS: RAMIE has the superiorities over MIE in short-term outcomes in terms of pneumonia and vocal cord palsy. Therefore, RAMIE could be considered as a standard treatment for patients with esophageal cancer.

Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China.

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.

Enteral immunonutrition versus enteral nutrition for patients undergoing esophagectomy: a randomized controlled trial.

BACKGROUND: In recent years, immunonutrition has been introduced and proposed to have a positive modulatory effect on inflammatory and immune responses and gut function for surgical patients, especially for patients undergoing gastrointestinal cancer resection. We conducted this parallel-group, randomized and double-blind clinical controlled trial to investigate the efficacy of perioperative enteral immunonutrition (EIN) on clinical and immunological outcomes of patients undergoing esophageal resection. METHODS: A randomized, parallel-group, double-blind, clinical trial was conducted between December 1, 2017 and March 1, 2018. This study enrolled 120 patients with esophageal cancer. And 112 patients were divided into two groups randomly: EIN group and enteral nutrition (EN) group. The EIN contained extra immunonutritional substrates, including a consistent combination of arginine, RNA and the omega-3 fatty acids compared with EN. Immune indicators were measured at preoperative day 7, postoperative day (POD) 1, 3, 7 and post-discharge day (PDD) 30. RESULTS: There were 56 participants randomized to each group. Finally, 53 patients in EIN and 50 patients in EN were analyzed. Immune indicator was the primary outcome in this study. EIN yielded a significantly lower rate of CD8/CD3 (%) at POD 3 compared with EN group (P=0.005). The rate of CD4/CD8 (%) in EIN group was higher than that in EN group at POD3 (P=0.004). The serum levels of IgM at POD 3 and 7 were significantly higher in EN group compared with EIN group (P=0.025 and P=0.009, respectively). The rate of NK (%) and the serum level of IgA were significantly higher in EIN group compared with EN group at PDD 30 (P=0.022 and P=0.041, respectively). No significant differences were found in 2-year progressionfree survival and overall survival. CONCLUSIONS: Immunonutrition is a safe and feasible nutritional treatment, which has a positive modulatory impact on immune responses after esophagectomy. Although no significant difference was found in clinical and survival outcomes between EIN and EN groups, immunonutrition could still have a positive effect on immunological function of patients undergoing esophagectomy.

Clinical efficacy of robot-assisted thoracoscopic surgery for posterior mediastinal neurogenic tumors.

BACKGROUND: Robot-assisted thoracic surgery (RATS) has an increasing usage throughout the world. This retrospective cohort study aimed to objectively compare the surgical results between video-assisted thoracic surgery (VATS) and RATS in posterior mediastinal neurogenic tumors (PMNT). METHODS: We retrospectively reviewed the clinical data of 130 patients diagnosed with posterior mediastinal neurogenic tumor between 2015 and 2018. Magnetic resonance imaging (MRI) or enhanced computed tomography scan (CT-scan) was used to locate the tumor and investigate the Adamkiewicz's artery preoperatively. The individual surgical approach was determined by both tumor size and patient's willings. RESULTS: The surgical time in RATS (43.2±12.6 min) was tended to be less than that in VATS (47.4±11.9 min) (P=0.054). Meanwhile, the estimated blood loss in RATS group (85.8±22.6 mL) was significantly less than that in VATS group (95.3±28.4 mL) (P=0.040). However, the duration of chest tube (days) and volume of drainage (mL) had no significant difference between two groups (P=0.12 and P=0.68, respectively). The postoperative hospital stay (days) of patients in RATS group (2.2±0.4 days) was significantly shorter than that in VATS group (2.4±0.6 days) (P=0.031). There were no significant differences between two groups in the incidence of the postoperative complications and adverse reactions. CONCLUSIONS: RATS has the superiorities in terms of surgical blood loss and postoperative hospital stay over VATS for posterior mediastinal neurogenic tumor. In conclusion, RATS could be a feasible and safe way for resecting posterior mediastinal neurogenic tumor.