ABSTRACT
BACKGROUND: Higher outdoor temperature may be related to an increase in antibiotic resistant bacteria. We investigated the association between local outdoor air temperature and the incidence of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) correcting for known drivers of antibiotic resistance. METHODS: We performed a time-series regression study using prospectively collected weekly surveillance data on all ESBL-PE isolated from in- and outpatients of the University Hospital Basel, a tertiary care center in Switzerland, between 01/2008-12/2017. Temperature was measured hourly at the meteorological institute of the University Basel next to our institution over this time period. A time-series approach using a Poisson regression model and different lag terms for delayed exposure effects was performed to assess associations between minimal, mean and maximal weekly temperature and the number of ESBL-PE recovered. RESULTS: Over 10 years, recovery of ESBL-PE increased (annual incidence rate ratio [IRR] 1.14, 95%CI 1.13-1.16), while mean weekly temperature measures remained stable. In multivariable analyses, increasing temperature was associated with higher recovery rates of ESBL-PE after three to four weeks, correcting for potential confounders, such as the number of admissions, proportion of long-term nursing facility- and ICU-admissions, age, Charlson comorbidity index and consumption of antimicrobials (IRRs per 10 °C ranging from 1.14 to 1.22, 95%CIs 1.07-1.33). These trends remained when analyzing correlations between temperature with the proportion of extended spectrum cephalosporin resistance of all recovered Enterobacteriaceae. CONCLUSIONS: Higher outdoor temperature may be associated with an increase of ESBL-PE-incidence, independent of important confounders, such as antimicrobial consumption and thus should be considered for future resistance-trajectories.
Subject(s)
Enterobacteriaceae , beta-Lactamases , Anti-Bacterial Agents/pharmacology , Enterobacteriaceae/drug effects , Humans , Risk Factors , TemperatureABSTRACT
BACKGROUND: We aimed to directly compare preoperative high-sensitivity cardiac troponin (hs-cTn) I and T concentration for the prediction of major cardiac complications after non-cardiac surgery. METHODS: We measured hs-cTnI and hs-cTnT preoperatively in a blinded fashion in 1022 patients undergoing non-cardiac surgery. The primary endpoint was a composite of major cardiac complications including cardiac death, cardiac arrest, myocardial infarction, clinically relevant arrhythmias, and acute heart failure within 30 days. We hypothesized that the type of surgery may impact on the predictive accuracy of hs-cTnI/T and stratified all analyses according to the type of surgery. RESULTS: Major cardiac complications occurred in 108 (11%) patients, 58/243 (24%) patients undergoing vascular surgery and 50/779 (6%, Pâ¯<â¯.001) patients undergoing non-vascular surgery. Using regulatory-approved 99th percentile cut-off concentrations, preoperative hs-cTnI elevations were less than one-fifth as common as preoperative hs-cTnT elevations (Pâ¯<â¯.001). Among patients undergoing vascular surgery, preoperative hs-cTnI concentrations, but not hs-cTnT, was an independent predictor of cardiac complications (adjusted odds ratio (aOR) 1.5, 95% confidence interval (95% CI) 1.0-2.1). The area under the receiver-operating characteristics curve (AUC) was 0.67 (95% CI, 0.59-0.75) for hs-cTnI versus 0.59 (95% CI 0.51-0.67, Pâ¯=â¯.012) for hs-cTnT. In contrast, among patients undergoing non-vascular surgery both preoperative hs-cTnI and hs-cTnT were independent predictors of the primary endpoint (aOR 1.6, 95% CI 1.3-2.0, and aOR 3.0, 95% CI 2.0-4.6, respectively) and showed higher predictive accuracy (AUC 0.77, 95% CI, 0.71-0.83, and 0.79, 95% CI 0.73-0.85, Pâ¯=â¯ns). CONCLUSIONS: Preoperative hs-cTnI and hs-cTnT concentrations predict major cardiac complications after non-vascular surgery, while, in patients undergoing vascular surgery, hs-cTnI may have better accuracy.
Subject(s)
Myocardial Infarction/blood , Postoperative Complications/blood , Surgical Procedures, Operative/adverse effects , Troponin I/blood , Troponin T/blood , Aged , Biomarkers/blood , Brazil/epidemiology , Coronary Angiography , Echocardiography , Electrocardiography , Female , Follow-Up Studies , Humans , Immunoassay , Incidence , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Perfusion Imaging , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Predictive Value of Tests , ROC Curve , Retrospective Studies , Survival Rate/trends , Switzerland/epidemiology , Time FactorsABSTRACT
Amino acid (AA) uniporter Lat4 (Slc43a2) mediates facilitated diffusion of branched-chain AAs, methionine and phenylalanine, although its physiological role and subcellular localization are not known. We report that Slc43a2 knockout mice were born at expected Mendelian frequency but displayed an â¼10% intrauterine growth retardation and low amniotic fluid AAs, suggesting defective transplacental transport. Postnatal growth was strongly reduced, with premature death occurring within 9 days such that further investigations were made within 3 days of birth. Lat4 immunofluorescence showed a strong basolateral signal in the small intestine, kidney proximal tubule and thick ascending limb epithelial cells of wild-type but not Slc43a2 null littermates and no signal in liver and skeletal muscle. Experiments using Xenopus laevis oocytes demonstrated that Lat4 functioned as a symmetrical low affinity uniporter with a K0.5 of â¼5 mm for both in- and efflux. Plasma AA concentration was decreased in Slc43a2 null pups, in particular that of non-essential AAs alanine, serine, histidine and proline. Together with an increased level of plasma long chain acylcarnitines and a strong alteration of liver gene expression, this indicates malnutrition. Attempts to rescue pups by decreasing the litter size or by nutrients injected i.p. did not succeed. Radioactively labelled leucine but not lysine given per os accumulated in the small intestine of Slc43a2null pups, suggesting the defective transcellular transport of Lat4 substrates. In summary, Lat4 is a symmetrical uniporter for neutral essential AAs localizing at the basolateral side of (re)absorbing epithelia and is necessary for early nutrition and development.