Background Multiple authors have reported that “general anesthesia”(GA), as a generic and uncharacterized therapy, is contraindicated for patients undergoing endovascular management of acute ischemic stroke(EMAIS). The recent AHA update cautiously suggests that it might be reasonable to favor conscious sedation over GA during EMAIS. We are concerned that such recommendations will result in patients undergoing endovascular treatment without consideration of the effects of specific anesthetic agents, anesthetic dose, nor appropriate critical consideration of the individual patient's issues. We hypothesized that significant variation in anesthetic practice comprises GA and that outcome differences among types of GA would arise. Methods With IRB approval we examined records of patients who underwent anterior circulation EMAIS at UPenn from 2010 to 2015. Patients were managed by different anesthesiologists with no specific protocol. We analyzed ASA status, NIHSS, type of stroke, procedure, different types of anesthetic, blood pressure control, and outcome metrics. Modified Rankin Scales(mRS) were determined from medical records. Results GA was used in 91% of patients. Several types of GA were employed: intravenous(TIVA), volatile, and intravenous/volatile(combined). mRS scores ≤2 at discharge were observed in 42.8% of our patients receiving volatile anesthesia and were better in patients receiving only volatile agents after induction of anesthesia (P<0.05). Conclusion Our data support the notion that anesthetic techniques and associated physiology used in EMAIS are not homogenous, making any statements about the effects of generic “GA” in stroke ambiguous. Moreover, our data suggest that the type of GA may affect outcome after EMAIS.

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_03_15_CJASNPodcast_18_4_M.mp3.

Background: Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture. Methods: Using private health insurance claims data from Optum’s de-identified Clinformatics Data Mart database from January 1, 2000, to September 30, 2015, we identified adults with a single long-bone fracture or commonly paired long-bone fractures who had 1 year of available follow-up data. Using multivariable logistic regression models, we examined associations between NSAID, COX-2-inhibitor, or opioid prescription fills after the fracture and the risk of nonunion within 1 year, defined as a nonunion diagnosis with a procedure to treat the nonunion. Results: A nonunion diagnosis with a procedure to treat the nonunion was identified after 2,996 (0.9%) of the 339,864 fracture episodes, with rates varying by fracture site. The risk of that outcome was greater in patients who had filled COX-2-inhibitor prescriptions (adjusted odds ratio = 1.84 [95% confidence interval = 1.38 to 2.46]) or opioid prescriptions (1.69 [1.53 to 1.86]), but not in patients who had filled nonselective-NSAID prescriptions (1.07 [0.93 to 1.23]) after the fracture. Results were similar when the outcome definition was changed to just a nonunion diagnosis. Conclusions: COX-2 inhibitors, but not nonselective NSAIDs, were associated with a greater risk of nonunion after fracture. Opioids were also associated with nonunion risk, although patients filling prescriptions for opioids may have had more severe fractures. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Tacrolimus exhibits unpredictable pharmacokinetics after lung transplant, partly explained by CYP-enzyme polymorphisms. However, whether exposure variability during the immediate postoperative period affects outcomes is unknown, and pharmacogenetic dosing may be limited by residual pharmacokinetic variability. We estimated adjusted associations between early postoperative tacrolimus concentrations and acute kidney injury (AKI) and acute cellular rejection (ACR), and identified clinical and pharmacogenetic factors that explain post-operative tacrolimus concentration variability in 484 lung transplant patients. Increasing tacrolimus concentration was associated with higher AKI risk: HR 1.54, (95%CI 1.20-1.96) per 5-mg/dL; and increasing AKI

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.

There is significant variability in the serum concentrations of tacrolimus attained early post-transplant due to drug interactions and genomic variation. We evaluated whether tacrolimus concentrations early post-transplant correlate with incidence of acute graft-versus-host disease in 120 consecutive patients allografted with a uniform reduced-intensity conditioning regimen. All patients received standard prophylaxis with oral tacrolimus and intravenous methotrexate. The primary variable of interest was mean weekly tacrolimus concentrations in the initial 4 weeks post-transplant. In multivariate analysis, week 1 tacrolimus concentration was an independent predictor of acute grade 2 – 4 graft-versus-host disease (HR, .90; 95% CI, .84 to .97; P < .01). This association was driven by a lower risk of acute grade 2 – 4 graft-versus-host disease in patients with week 1 tacrolimus concentrations >12 ng/mL (HR .47; 95% CI, .25 – .88; P = .02). Week 1 tacrolimus concentrations were not associated with chronic graft-versus-host disease, relapse, or overall survival. Lower tacrolimus concentrations at weeks 2, 3, and 4 were not associated with a higher incidence of graft-versus-host disease. In summary, we found that higher tacrolimus concentrations during the first week after allografting with a reduced-intensity conditioning regimen were associated with significantly reduced risk of acute grade 2 – 4 graft-versus-host disease without increasing risk of relapse.

Purpose: Although dozens of studies have associated vancomycin + piperacillin-tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion. Methods:We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin-tazobactam or vancomycin + cefepime. Kidney function biomarkers [creatinine, cystatin C, and blood urea nitrogen (BUN)] were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates.Results: The study included 739 patients (vancomycin + piperacillin-tazobactam n = 297, vancomycin + cefepime n = 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin-tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatininedefined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin-tazobactam was not associated with change in alternative biomarkers: cystatin C:

The microbiological similarities of rapidly growing mycobacteria and corynebacteria impose potential for misidentification in the laboratory. This report describes a fatal case of infectious endocarditis caused by Mycobacterium abscessus, initially identified and treated as Corynebacterium spp. Acid-fast staining should be performed routinely when multiple blood cultures grow Corynebacterium spp.