FIB-4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC-IV database.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them. METHODS: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups. RESULTS: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]. CONCLUSION: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.

Simvastatin ameliorates synaptic plasticity impairment in chronic mild stress-induced depressed mice by modulating hippocampal NMDA receptor.

BACKGROUND: In our previous study, we showed simvastatin exerts an antidepressant effect and inhibits neuroinflammation. Given the role of synaptic impairment in depression development, we investigate the effect of simvastatin on synaptic plasticity in depression and the related mechanisms. METHODS: Electrophysiological analysis, Golgi staining, and transmission electron microscope were performed to analyze the effect of simvastatin on synaptic impairment in depression. In addition, the localization and reactivity of N-methyl-D-aspartate receptor (NMDAR) subunits and the downstream signaling were investigated to explore the mechanism of simvastatin's effect on synaptic plasticity. RESULTS: Simvastatin ameliorated the reduction of the magnitude of long-term potentiation (LTP) in Schaffer collateral-CA1, restored hippocampal dendritic spine density loss, improved the number of spine synapses, reversed the reduction in BrdU-positive cells in chronic mild stress (CMS)-induced depressed mice, and ameliorated NMDA-induced neurotoxicity in hippocampal neurons. Dysfunction of NMDAR activity in the hippocampus is associated with depression. Simvastatin treatment reversed the surface expression and phosphorylation changes of NMDAR subunits in NMDA-treated hippocampal neurons and depressed mice. In addition, simvastatin further increased the levels of mature BDNF, activating TrkB-Akt-mTOR signaling, which is critical for synaptic plasticity. CONCLUSIONS: These findings suggest that simvastatin can improve the dysfunction of NMDAR and ameliorate hippocampal synaptic plasticity impairment in depressed mice.

DECREASE IN THE PLATELET-TO-LYMPHOCYTE RATIO IN DAYS AFTER ADMISSION FOR SEPSIS CORRELATES WITH IN-HOSPITAL MORTALITY.

ABSTRACT: Background: A previous study has linked an increase in platelet-to-lymphocyte ratio (PLR) to a poor prognosis; however, the relationship between early change in PLR and outcomes in sepsis patients is unclear. Methods : The Medical Information Mart for Intensive Care IV database was for this retrospective cohort analysis on patients meeting the Sepsis-3 criteria. All the patients meet the Sepsis-3 criteria. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count. We collected all PLR measurements that were available within 3 days of admission for analysis of longitudinal changes over time. Multivariable logistic regression analysis was used to determine the relationship between the baseline PLR and in-hospital mortality. After correcting for possible confounders, the generalized additive mixed model was used to examine the trends in PLR over time among survivors and nonsurvivors. Results: Finally, 3,303 patients were enrolled, and both low and high PLR levels were significantly associated with higher in-hospital mortality in the multiple logistic regression analysis (tertile 1: odds ratio, 1.240; 95% confidence interval, 0.981-1.568 and tertile 3: odds ratio, 1.410; 95% confidence interval, 1.120-1.776, respectively). The generalized additive mixed model results revealed that the PLR of the nonsurvival group declined faster than that of the survival group within 3 days after intensive care unit admission. After controlling for confounders, the difference between the two groups steadily decreased and increased by an average of 37.38 daily. Conclusions : There was a U-shaped relationship between the baseline PLR and in-hospital mortality of sepsis patients, and there was a significant difference between the nonsurvival and survival groups in the change in PLR over time. The early decrease in PLR was related to an increase in in-hospital mortality.

Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy.

Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28-6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1-1.5 million IU/day, given in 2-3 doses, could attain PTA > 90% for MICs ≤ 0.5 µg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 µg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 µg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 µg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.

Association of FIB-4 index and clinical outcomes in critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and clinical outcomes in patients with acute kidney injury (AKI) is unclear. We aimed to investigate the association between FIB-4 index and all-cause mortality in critically ill patients with AKI. METHODS: We used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). The FIB-4 score was calculated using the existing formulas. logistic regression model, and Cox proportional hazards model were used to assessed the relationship between the FIB-4 index and in-hospital,28-day and 90-day mortality, respectively. RESULTS: A total of 3592 patients with AKI included in the data analysis. 395 (10.99%) patients died during hospitalization and 458 (12.74%) patients died in 28-day. During the 90-day follow-up, 893 (22.54%) patients were dead. An elevated FIB-4 value was significantly associated with increased in-hospital mortality when used as a continuous variable (odds ratio [OR] 1.183, 95% confidence interval [CI] 1.072-1.305, P = 0.002) and as a quartile variable (OR of Q2 to Q4 1.216-1.744, with Q1 as reference). FIB-4 was positively associated with 28-day mortality of AKI patients with hazard ratio (HR) of 1.097 (95% CI 1.008, 1.194) and 1.098 (95% 1.032, 1.167) for 90-day mortality, respectively. CONCLUSION: This study demonstrated the FIB-4 index is associated with clinical outcomes in critically ill patients with acute kidney injury.

Model Based Identification of Linezolid Exposure-toxicity Thresholds in Hospitalized Patients.

Evidence supports linezolid therapeutic drug monitoring as the exposure-response relationship has been identified for toxicity among patients receiving linezolid, but the data to establish the upper limit are limited and the published toxicity thresholds range widely. The purpose of this study was to determine the linezolid exposure-toxicity thresholds to improve the safety of linezolid. This is a multicenter retrospective study of adult patients treated with linezolid from 2018 to 2019. The population pharmacokinetic model of linezolid was established based on 270 plasma concentrations in 152 patients, which showed creatinine clearance and white cell count are covariates affecting the clearance of linezolid, and serum albumin is the covariate affecting the volume of distribution. Classification and regression tree analysis was used to determine the linezolid exposure thresholds associated with an increased probability of toxicity. Among 141 patients included for toxicity analysis, the rate of occurring toxicity was significantly higher among patients with an AUC0-24, d1 ≥163 mg h/L, AUC0-24, d2 ≥207 mg h/L, AUC0-24, ss ≥210 mg h/L, and Cmin,d2 ≥6.9 mg/L, Cmin,ss ≥6.9 mg/L, while no threshold was discovered for Cmin, d1. Those exposure thresholds and duration of linezolid treatment were independently associated with linezolid-related toxicity in the logistic regression analyses. In addition, the predictive performance of the AUC0-24 and Cmin thresholds at day 2 and steady state were close. Considering that the AUC estimation is cumbersome, Cmin threshold at 48 h and steady state with a value of ≥6.9 mg/L is recommended to improve safety, especially for patients with renal insufficiency and patients with low serum albumin.

Accurate prediction of acute pancreatitis severity with integrative blood molecular measurements.

BACKGROUND: Early diagnosis of severe acute pancreatitis (SAP) is essential to minimize its mortality and improve prognosis. We aimed to develop an accurate and applicable machine learning predictive model based on routine clinical testing results for stratifying acute pancreatitis (AP) severity. RESULTS: We identified 11 markers predictive of AP severity and trained an AP stratification model called APSAVE, which classified AP cases within 24 hours at an average area under the curve (AUC) of 0.74 +/- 0.04. It was further validated in 568 validation cases, achieving an AUC of 0.73, which is similar to that of Ranson's criteria (AUC = 0.74) and higher than APACHE II and BISAP (AUC = 0.69 and 0.66, respectively). CONCLUSIONS: We developed and validated a venous blood marker-based AP severity stratification model with higher accuracy and broader applicability, which holds promises for reducing SAP mortality and improving its clinical outcomes. MATERIALS AND METHODS: Nine hundred and forty-five AP patients were enrolled into this study. Clinical venous blood tests covering 65 biomarkers were performed on AP patients within 24 hours of admission. An SAP prediction model was built with statistical learning to select biomarkers that are most predictive for AP severity.

Anatomical and Pathological Observation and Analysis of SARS and COVID-19: Microthrombosis Is the Main Cause of Death.

The spread of the coronavirus (SARS-CoV-2, COVID-19 for short) has caused a large number of deaths around the world. We summarized the data reported in the past few months and emphasized that the main causes of death of COVID-19 patients are DAD (Diffuse Alveolar Damage) and DIC (Disseminated intravascular coagulation). Microthrombosis is a prominent clinical feature of COVID-19, and 91.3% of dead patients had microthrombosis.Endothelial damage caused by SARS-CoV-2 cell invasion and subsequent host response disorders involving inflammation and coagulation pathways play a key role in the progression of severe COVID-19. Microvascular thrombosis may lead to microcirculation disorders and multiple organ failure lead to death.The characteristic pathological changes of DAD include alveolar epithelial and vascular endothelial injury, increased alveolar membrane permeability, large numbers of neutrophil infiltration, alveolar hyaline membrane formation, and hypoxemia and respiratory distress as the main clinical manifestations. DAD leads to ARDS in COVID-19 patients. DIC is a syndrome characterized by the activation of systemic intravascular coagulation, which leads to extensive fibrin deposition in the blood. Its occurrence and development begin with the expression of tissue factor and interact with physiological anticoagulation pathways. The down-regulation of fibrin and the impaired fibrinolysis together lead to extensive fibrin deposition.DIC is described as a decrease in the number of platelets and an increase in fibrin degradation products, such as D-dimer and low fibrinogen. The formation of microthrombus leads to the disturbance of microcirculation, which in turn leads to the death of the patient. However, the best prevention and treatment of COVID-19 microthrombosis is still uncertain.This review discusses the latest findings of basic and clinical research on COVID-19-related microthrombosis, and then we proposed the theory of microcirculation perfusion bundle therapy to explore effective methods for preventing and treating COVID-19-related microthrombosis. Further research is urgently needed to clarify how SARS-CoV-2 infection causes thrombotic complications, and how it affects the course and severity of the disease. To cultivate a more comprehensive understanding of the underlying mechanism of this disease. Raise awareness of the importance of preventing and treating microthrombosis in patients with COVID-19.

Population pharmacokinetic and optimization of polymyxin B dosing in adult patients with various renal functions.

AIMS: Current FDA-approved label recommends that the dosage of polymyxin B should be adjusted according to renal function. However, the correlation between polymyxin B pharmacokinetics (PK) and creatinine clearance (CrCL) is poor. This study aimed to develop a population PK model of polymyxin B in adult patients with various renal functions and to identify a dosing strategy. METHODS: A retrospective PK study was performed in 32 adult patients with various renal function. Nonlinear mixed effects modelling was applied to build a population PK model of polymyxin B followed by Monte Carlo simulations which designed polymyxin B dosing regimens across various renal function. RESULTS: Polymyxin B PK analyses included 112 polymyxin B concentrations at steady state from 32 adult patients, in which 71.9% of them were critically ill. In the final PK model, CrCL was the significant covariate on CL (typical value 1.59 L/h; between-subject variability 13%). The mean (SD) individual empirical Bayesian estimate of CL was 1.75 (0.43) L/h. In addition, a new dosing strategy combining the PK/pharmacodynamic (PD) targets and Monte Carlo simulation indicated that the reduction of polymyxin B dose in patients with renal insufficiency improved the probability of achieving optimal exposure. For severe infections caused by organisms with minimum inhibitory concentration (MIC) ≥ 2 mg/L, a high daily dose of polymyxin B might be possible for bacterial eradication, but the risk of nephrotoxicity is increased. CONCLUSIONS: Renal function plays a significant role in polymyxin B PK, and the dose of polymyxin B should be adjusted according to CrCL in patients with renal insufficiency.

Clinical Characteristics and Outcomes of Severe and Critical Patients With 2019 Novel Coronavirus Disease (COVID-19) in Wenzhou: A Retrospective Study.

Information about severe cases of 2019 novel coronavirus disease (COVID-19) infection is scarce. The aim of this study was to report the clinical characteristics and outcomes of severe and critical patients with confirmed COVID-19 infection in Wenzhou city. In this single-centered, retrospective cohort study, we consecutively enrolled 37 RT-PCR confirmed positive severe or critical patients from January 28 to February 16, 2020 in a tertiary hospital. Outcomes were followed up until 28-day mortality. Fifteen severe and 22 critical adult patients with the COVID-19 infection were included. Twenty-six (68.4%) were men. Echocardiography data results suggest that normal or increased cardiac output and diastolic dysfunction are the most common manifestations. Compared with severe patients, critical patients were older, more likely to exhibit low platelet counts and high blood urea nitrogen, and were in hospital for longer. Most patients had organ dysfunction during hospitalization, including 11 (29.7%) with ARDS, 8 (21.6%) with acute kidney injury, 17 (45.9%) with acute cardiac injury, and 33 (89.2%) with acute liver dysfunction. Eighteen (48.6%) patients were treated with high-flow ventilation, 9 (13.8%) with non-invasive ventilation, 10 (15.4%) with invasive mechanical ventilation, 7 (18.9%) with prone position ventilation, 6 (16.2%) with extracorporeal membrane oxygenation (ECMO), and 3 (8.1%) with renal replacement therapy. Only 1 (2.7%) patient had died in the 28-day follow up in our study. All patients had bilateral infiltrates on their chest CT scan. Twenty-one (32.3%) patients presented ground glass opacity (GGO) with critical patients more localized in the periphery and the center. The mortality of critical patients with the COVID-19 infection is low in our study. Cardiac function was enhanced in the early stage and less likely to develop into acute cardiac injury, but most patients suffered with acute liver injury. The CT imaging presentations of COVID-19 in critical patients were more likely with consolidation and bilateral lung involvement.

A narrative review of driving pressure as a monitoring indicator during mechanical ventilation with spontaneous breathing.

The mortality of acute respiratory distress syndrome (ARDS) remains high, and mechanical ventilation (MV) is an essential means of treatment. During MV, people realize the benefits of spontaneous breathing and the disadvantages of uncontrolled spontaneous breathing. Current methods of monitoring spontaneous breathing include oesophageal manometry, P0.1, and diaphragm function monitoring. However, these methods have limitations and deficiencies. The driving pressure is a new indicator that reflects the strain of the lung, which indicates the volumetric injury of the lung and is independently associated with mortality in ARDS patients. Moreover, in recent studies, driving pressure monitoring has been shown to be feasible in assisted support ventilation. This review summarizes the current state of spontaneous breathing and examines whether it is convenient to monitor driving pressure during spontaneous breathing to achieve lung protection ventilation.

Red blood cell distribution width is associated with mortality risk in patients with acute respiratory distress syndrome based on the Berlin definition: A propensity score matched cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder of the lungs and is associated with oxidative damage. However, red blood cell distribution width (RDW), as an indicator of body response to inflammation and oxidative stress, has not been studied for its relationship with ARDS as diagnosed by the Berlin definition. OBJECTIVES: To examine the value of RDW in predicting the prognosis of in patients with ARDS. METHODS: This is a retrospective study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Berlin-defined ARDS patients using mechanical ventilation for more than 48 hours were selected using structured query language. The primary statistical methods were propensity score matching and sensitivity analysis, including an inverse probability weighting model to ensure the robustness of our findings. RESULTS: A total of 529 intensive care unit (ICU) patients with ARDS according to the Berlin definition were enrolled in the study. The adjusted OR showed an adverse effect between the higher RDW group and 30-day mortality [OR 2.33, 95% CI (1.15-4.75), P=0.019]. However, we found that length of ICU stay was not related to RDW (P=0.167), and in the anaemia group, RDW was poorly predictive of 30-day mortality (P=0.307). CONCLUSION: In unselected ARDS patients, higher RDW was associated with higher 30-day mortality rate. Further investigation is required to validate this relationship with prospectively collected data.

The association of coagulation indicators with in-hospital mortality and 1-year mortality of patients with sepsis at ICU admissions: A retrospective cohort study.

BACKGROUND: Coagulation activation is the host's response to pathogens during sepsis and is considered to be one of the reasons for tissue damage and multiple organ failure. This study is designed to evaluate whether the alterations of coagulation indicators are related to in-hospital mortality and 1-year mortality of patients with sepsis. METHOD: Data of all 2258 patients were extracted from the database Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). The relationship between the in-hospital mortality of patients with sepsis and coagulation indicators was analyzed with a receiver operating characteristic (ROC) curve analysis and logistic regression model. Effects of coagulation indicators on patients' 1-year mortality were determined by using a Cox hazard regression model, and clinical experience or quintiles were used to classify the activated partial thromboplastin time (APTT) to determine the cutoff values to explore segmentation effects. RESULT: International normalized ratio (INR) was positively associated with hospital mortality of patients with sepsis after adjusting confounders with an odds ratio (OR) of 1.86 [95% confidence interval (CI), 1.37-2.52], and a hazard ratio (HR) of 1.465[95%CI(1.24-1.74)] for 1-year mortality, respectively. 1-year mortality of patients with sepsis demonstrated a U-shaped relationship with APTT, ranging from 25 to 37, indicating the lowest risk. The adjusted HR (95% CI) values for 1-year mortality of septic patients with risk values <25 and >37 were 1.493 (1.02, 2.19) and 1.379 (1.06, 1.79), respectively. CONCLUSION: Increased INR in critically ill septic patients is related to greater in-hospital mortality and 1-year mortality. A U-shaped relationship was found between APTT and 1-year mortality of patients with sepsis.

Nomogram for predicting diabetes mellitus after the first attack of acute pancreatitis.

BACKGROUND: Diabetes mellitus can occur after acute pancreatitis (AP), but there are currently no tools for evaluating the risk of developing diabetes after an attack of AP. The aim of the study was to develop a nomogram for prediction of new-onset diabetes mellitus after the first attack of AP. PATIENTS AND METHODS: We enrolled 616 patients with first-attack AP. We collected and statistically analyzed demographic data (age, BMI, and duration of hospitalization) and laboratory data (glucose, low-density lipoprotein cholesterol, triglyceride, and cholesterol). RESULTS: Univariate analysis suggested duration of hospitalization (P=0.0003), BMI (P=0.0059), cholesterol (P=0.0005), triglyceride (P=0.0005), hemoglobin (P=0.0229), and glucose (P<0.001) at admission were significantly associated with newly developed diabetes after the first-attack AP. Multivariate analysis showed that age [odds ratio (OR)=1.01; 95% confidence interval (CI): 1.00-1.03; P=0.045], BMI (OR=1.06; 95% CI: 1.01-1.12; P=0.018), glucose (OR=1.07; 95% CI: 1.02-1.12; P=0.008), triglyceride (OR=1.03; 95% CI: 1.00-1.06; P=0.035), and low-density lipoprotein-cholesterol (OR=1.18; 95% CI: 1.00-1.38; P=0.044) at admission were important predictors. CONCLUSION: The nomogram is a potentially clinically useful tool for predicting new-onset diabetes, which is currently clinically unprecedented. This finding is not confined to the patients with severe AP but is also for patients who have recovered from mild AP. The nomogram must to be validated externally.

Prognostic value of platelet-to-lymphocyte ratios among critically ill patients with acute kidney injury.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute kidney injury (AKI). However, evidence regarding the prognostic effect of the platelet-to-lymphocyte ratio (PLR), a novel systemic inflammation marker, among patients with AKI is scarce. In this study, we investigated the value of the PLR in predicting the outcomes of critically ill patients with AKI. METHODS: Patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.3. PLR cutoff values were determined using smooth curve fitting or quintiles and were used to categorize the subjects into groups. The clinical outcomes were 30-day and 90-day mortality in the intensive care unit (ICU). Cox proportional hazards models were used to evaluate the association between the PLR and survival. RESULTS: A total of 10,859 ICU patients with AKI were enrolled. A total of 2277 thirty-day and 3112 ninety-day deaths occurred. A U-shaped relationship was observed between the PLR and both 90-day and 30-day mortality, with the lowest risk being at values ranging from 90 to 311. The adjusted HR (95% CI) values for 90-day mortality given risk values < 90 and > 311 were 1.25 (1.12-1.39) and 1.19 (1.08-1.31), respectively. Similar trends were observed for 30-day mortality or when quintiles were used to group patients according to the PLR. Statistically significant interactions were found between the PLR and both age and heart rate. Younger patients (aged < 65 years) and those with more rapid heart rates (≥89.4 beats per minute) tended to have poorer prognoses only when the PLR was < 90, whereas older patients (aged ≥ 65 years) and those with slower heart rates (<89.4 beats per minute) had higher risk only when the PLR was > 311 (P < 0.001 for age and P < 0.001 for heart rate). CONCLUSIONS: The preoperative PLR was associated in a U-shaped pattern with survival among patients with AKI. The PLR appears to be a novel, independent prognostic marker of outcomes in critically ill patients with AKI.

High prevalence of plasmid-mediated 16S rRNA methylase gene rmtB among Escherichia coli clinical isolates from a Chinese teaching hospital.

BACKGROUND: Recently, production of 16S rRNA methylases by Gram-negative bacilli has emerged as a novel mechanism for high-level resistance to aminoglycosides by these organisms in a variety of geographic locations. Therefore, the spread of high-level aminoglycoside resistance determinants has become a great concern. METHODS: Between January 2006 and July 2008, 680 distinct Escherichia coli clinical isolates were collected from a teaching hospital in Wenzhou, China. PCR and DNA sequencing were used to identify 16S rRNA methylase and extended-spectrum beta-lactamase (ESBL) genes, including armA and rmtB, and in situ hybridization was performed to determine the location of 16S rRNA methylase genes. Conjugation experiments were subsequently performed to determine whether aminoglycoside resistance was transferable from the E. coli isolates via 16S rRNA methylase-bearing plasmids. Homology of the isolates harboring 16S rRNA methylase genes was determined using pulse-field gel electrophoresis (PFGE). RESULTS: Among the 680 E. coli isolates, 357 (52.5%), 346 (50.9%) and 44 (6.5%) isolates were resistant to gentamicin, tobramycin and amikacin, respectively. Thirty-seven of 44 amikacin-resistant isolates harbored 16S rRNA methylase genes, with 36 of 37 harboring the rmtB gene and only one harboring armA. The positive rates of 16S rRNA methylase genes among all isolates and amikacin-resistant isolates were 5.4% (37/680) and 84.1% (37/44), respectively. Thirty-one isolates harboring 16S rRNA methylase genes also produced ESBLs. In addition, high-level aminoglycoside resistance could be transferred by conjugation from four rmtB-positive donors. The plasmids of incompatibility groups IncF, IncK and IncN were detected in 34, 3 and 3 isolates, respectively. Upstream regions of the armA gene contained ISCR1 and tnpU, the latter a putative transposase gene,. Another putative transposase gene, tnpD, was located within a region downstream of armA. Moreover, a transposon, Tn3, was located upstream of the rmtB. Nineteen clonal patterns were obtained by PFGE, with type H representing the prevailing pattern. CONCLUSION: A high prevalence of plasmid-mediated rmtB gene was found among clinical E. coli isolates from a Chinese teaching hospital. Both horizontal gene transfer and clonal spread were responsible for the dissemination of the rmtB gene.

Acupressure therapy inhibits the development of diabetic complications in Chinese patients with type 2 diabetes.

OBJECTIVES: The objectives of this study were to investigate the effects of acupressure therapy (AT) on the development and progression of diabetic complications in Chinese patients with type 2 diabetes (T2D). DESIGN AND METHODS: A total of 80 patients with T2D were recruited for a randomized clinical study of the effect of AT on the progression and development of diabetic complications, and 64 patients were followed up for 3 years. All patients with T2D were treated with regular medicines and participated in diet and exercise programs for the control of hyperglycemia and hypertension. The patients in the AT group received additional treatment of a 90-minute AT 4-6 times per week for 3 consecutive years. Their blood lipids, fasting glucose levels, and heart and kidney functions and nerve conduction velocity (NCV) were longitudinally monitored before and every 12 months after AT. RESULTS: Following AT therapy for 3 years, significantly lower levels of total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and higher levels of high-density lipoprotein-cholesterol (HDL-C) were observed and no significantly increased levels of serum creatinine and urine protein were detected in the AT group, as compared with that in controls. Furthermore, the mean values of NCV in the AT group at 2 years post-treatment were significantly greater than those of controls and were further elevated at the end of this study. Therefore, AT inhibited the progression of hyperlipidemia and improved diabetes-associated kidney function and neuropathy in Chinese patients with T2D. CONCLUSIONS: AT may be an effective nonpharmacological adjunctive strategy for alleviating the development and progression of T2D-related complications.