Crystal Growth of Quaternary AkRE2Si2S8 (Ak = Ca and Sr; RE = La-Tb) Thiosilicates Using Flux-Assisted Boron Chalcogen Mixture Method: Exploring X-ray Scintillation, Luminescence, and Magnetic Properties.

We report on the detailed structural analysis of a series of 11 new quaternary rare earths containing thiosilicates, AkRE2Si2S8 (Ak = Ca and Sr; RE = La, Ce, Pr, Nd, Sm, Gd, and Tb), synthesized using the flux-assisted boron chalcogen mixture method. High quality crystals were grown and used to determine their crystal structures by single crystal X-ray diffraction. All members of the AkRE2Si2S8 series crystallize in the trigonal crystal system with space group R3̅c (space group no. 167). Polycrystalline powders were used for physical property measurements, including magnetic susceptibility, diffuse reflectance in the UV-visible range, and scintillation. Magnetic measurements indicated that CaRE2Si2S8 (RE = Nd and Tb) exhibits paramagnetic behavior with a slightly negative Weiss constant. The band gaps of the materials were determined from diffuse reflectance data, and optical band gaps were estimated to be 2.5(1) and 2.9(1) eV for CaCe2Si2S8 and CaGd2Si2S8, respectively. CaCe2Si2S8, CaTb2Si2S8, and SrCe2Si2S8 exhibited intense green luminescence upon irradiation with 375 nm ultraviolet light and, furthermore, scintillated when exposed to X-rays. Radioluminescence measurements of CaCe2Si2S8 powder revealed green emission with an intensity approximately 14% of that emitted by bismuth germanium oxide powder.

Prospective assessment of humoral and cellular immune responses to a 3rd COVID-19 mRNA vaccine dose among immunocompromised individuals.

BACKGROUND: Improved COVID-19 prevention is needed for immunocompromised individuals. METHODS: Prospective study of healthcare workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccines and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFNγ/TNFα T-cell responses were assessed in a subset. RESULTS: 536 participants were included: 492 immunocompromised [(206 solid organ transplant (SOT), 128 autoimmune, 80 hematologic malignancy (HM), 48 solid tumor, 25 HIV], 44 HCW. D3 significantly increased Spike IgG levels among all, but SOT and HM participants had the lowest median antibody levels post-D3 (increase from 0.09 to 0.83 and 0.27 to 1.92, respectively), versus HCW and persons with HIV, autoimmune conditions, and solid tumors (increases from 4.44 to 19.79, 2.9 to 15.75, 3.82 to 16.32, and 4.1 to 25.54, respectively). Seropositivity post-D3 was lowest for SOT (49.0%) and HM (57.8%), versus others (>90% seropositive). Neutralization post-D3 was lowest among SOT and HM. Predictors of lower antibody levels included low baseline levels and shorter intervals between vaccines. T-cell responses against Spike increased significantly among HCW and non-significantly among immunocompromised individuals. CONCLUSIONS: D3 significantly improves serological but not T-cell responses among immunocompromised individuals. SOT and HM patients have suboptimal responses to D3.

Boron Chalcogen Mixture Method-Assisted Alkali Halide Flux Crystal Growth of an Extensive Family of Quaternary Rare Earth Transition-Metal Thiosilicates: Investigation of Their Structures and Magnetic Properties.

A series of transition-metal-containing rare earth thiosilicates, RE3TM0.5SiS7 (RE = Gd-Yb; TM = Fe, Co, Ni), was obtained via flux crystal growth utilizing the boron chalcogen mixture (BCM) method. The series includes the first reported ytterbium-containing thiosilicates crystallizing in this structure type. The thiosilicates crystallize in the hexagonal crystal system in space group P63. The use of the BCM method to synthesize phase-pure samples of the title compounds for magnetic measurements is discussed, highlighting how the approach avoids some of the difficulties that plague typical chalcogenide syntheses. Magnetic measurements demonstrate that some of the compounds order antiferromagnetically and exhibit transition temperatures below 15 K.

Crystal Structures and Property Measurements of Rare Earth Magnesium Thiosilicates Synthesized via Flux Crystal Growth Utilizing the Boron Chalcogen Mixture (BCM) Method.

Nine new rare earth magnesium-containing thiosilicates of the formula RE3Mg0.5SiS7 (Ln = Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er) were synthesized in an alkali halide flux using the boron chalcogen mixture (BCM) method. Crystals of high quality were produced, and their structures were determined by single-crystal X-ray diffraction. The compounds crystallize in the hexagonal crystal system in the P63 space group. Phase pure powders of the compounds were used for magnetic susceptibility measurements and for second-harmonic generation (SHG) measurements. Magnetic measurements indicate that Ce3Mg0.5SiS7, Sm3Mg0.5SiS7, and Dy3Mg0.5SiS7 exhibit paramagnetic behavior with a negative Weiss temperature over the 2-300 K temperature range. SHG measurements of La3Mg0.5SiS7 demonstrated SHG activity with an efficiency of 0.16 times the standard potassium dihydrogen phosphate (KDP).

Investigation of the pharmacokinetics and metabolic fate of Fasiglifam (TAK-875) in male and female rats following oral and intravenous administration.

The metabolism and pharmacokinetics of fasiglifam (TAK-875, 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid), a selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist, were studied following intravenous (5 mg/kg) and oral administration (10 and 50 mg/kg) to male and female Sprague Dawley rats.Following intravenous dosing at 5 mg/kg, peak observed plasma concentrations of 8.8/9.2 µg/ml were seen in male and female rats respectively.Following oral dosing, peak plasma concentrations at 1 h of ca. 12.4/12.9 µg/ml for 10 mg/kg and 76.2/83.7 µg/ml for 50 mg/kg doses were obtained for male and female rats respectively. Drug concentrations then declined in the plasma of both sexes with t1/2's of 12.4 (male) and 11.2 h (female). Oral bioavailability was estimated to be 85-120% in males and females at both dose levels.Urinary excretion was low, but in a significant sex-related difference, female rats eliminated ca. 10-fold more drug-related material by this route.Fasiglifam was the principal drug-related compound in plasma, with 15 metabolites, including the acyl glucuronide, also detected. In addition to previously identified metabolites, a novel biotransformation, that produced a side-chain shortened metabolite via elimination of CH2 from the acetyl side chain was noted with implications for drug toxicity.

A general semiparametric Bayesian discrete-time recurrent events model.

Event time variables are often recorded in a discrete fashion, especially in the case of patient-reported outcomes. This work is motivated by a study of illicit drug users, in which time to drug use cessation has been recorded as a number of whole months. Existing approaches for handling such discrete data include treating the survival times as continuous (with adjustments for inevitable tied outcomes), or using discrete models that omit important features like random effects. We provide a general Bayesian discrete-time proportional hazards model, incorporating a number of features popular in continuous-time models such as competing risks and frailties. Our model also provides flexible baseline hazards for time effects, as well as generalized additive models style semiparametric incorporation of other time-varying covariates. Our specific modeling choices enable efficient Markov chain Monte Carlo inference algorithms, which we provide to the user in the form of a freely available R package called $\texttt{brea}$. We demonstrate that our model performs better on our motivating substance abuse application than existing approaches. We also present a reproducible application of the $\texttt{brea}$ software to a freely available data set from a clinical trial of anesthesia administration methods.

There is detectable variation in the lipidomic profile between stable and progressive patients with idiopathic pulmonary fibrosis (IPF).

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. The pathophysiological pathways involved in IPF are not well understood. Abnormal lipid metabolism has been described in various other chronic lung diseases including asthma and chronic obstructive pulmonary disease (COPD). However, its potential role in IPF pathogenesis remains unclear. METHODS: In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to characterize lipid changes in plasma derived from IPF patients with stable and progressive disease. We further applied a data-independent acquisition (DIA) technique called SONAR, to improve the specificity of lipid identification. RESULTS: Statistical modelling showed variable discrimination between the stable and progressive subjects, revealing differences in the detection of triglycerides (TG) and phosphatidylcholines (PC) between progressors and stable IPF groups, which was further confirmed by mass spectrometry imaging (MSI) in IPF tissue. CONCLUSION: This is the first study to characterise lipid metabolism between stable and progressive IPF, with results suggesting disparities in the circulating lipidome with disease progression.

Rapid determination of the pharmacokinetics and metabolic fate of gefitinib in the mouse using a combination of UPLC/MS/MS, UPLC/QToF/MS, and ion mobility (IM)-enabled UPLC/QToF/MS.

The metabolism and pharmacokinetics of gefitinib (Iressa®, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholino-propoxy)quinazolin-4-amine), a selective thymidylate kinase inhibitor for the epidermal growth factor receptor (EGFR), was studied after IV and PO administration to male C57BL6 mice at 10 and 50 mg/kg respectively.The pharmacokinetics and metabolism of gefitinib were investigated using a range of rapid UHPLC-MS and UHPLC-IM-HRMS methods, using both reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC), to rapidly determine the drugs pharmacokinetics and metabolic fate.Rapid oral absorption resulted in peak plasma concentrations at 1 h of ca. 7 µg/mL, that declined with a half-life of 3.8 h (2.6 h for the IV route), and providing an estimated oral bioavailability of 53%. Gefitinib itself was the major circulating drug-related compound in plasma extracts, with a total of 11 metabolites identified.The urinary profiles determined using both HILIC and RP-UPLC-IM-MS detected gefitinib and 10 metabolites or 15 metabolites respectively including the detection of a number of novel glucuronide conjugates.Despite rapid, sub 5 min, LC profiling methods being employed metabolite coverage was shown to be high and compared well with that of previous studies.

Toy story: A cross-sectional survey of toy populations in tertiary neonatal units.

Thousands of babies are given toys for their zeroth birthday … But what happens if that baby is admitted to neonatal intensive care? In a global first, we describe the population of toys found in incubators on neonatal intensive care unit.

Golden retriever pigmentary uveitis: Challenges of diagnosis and treatment.

Pigmentary uveitis (PU), also known as Golden Retriever Pigmentary Uveitis (GRPU), is a common ocular condition of Golden Retrievers that has severe, vision-threatening ocular complications and can require surgical intervention. In order to ensure consistency in the diagnosis of GRPU between examiners, a specified set of diagnostic criteria must be applied. This is critical to ensure owners, breeders, and veterinary ophthalmologists maintain confidence in the ocular certification process. Therefore, current and former members of the American College of Veterinary Ophthalmologists' Genetics Committee came together to draft this Viewpoint Article on the challenges of diagnosis and treatment of Golden Retriever Pigmentary Uveitis for veterinary ophthalmologists, Golden Retriever owners, and Golden Retriever breeders.

Recovery Trajectory of Postural Control Impairments Following a Concussion: A Case Study.

CONTEXT: Altered postural control represents one of the most common motor consequences following a concussion and there is a paucity of data monitoring the recovery trajectory that identifies the persistent changes of postural control. OBJECTIVE: To determine whether the recovery trajectory of postural control was consistent across different measures of postural stability and whether increased postural challenge (ie, sloped surface) revealed subtle postural impairments. DESIGN: A single-subject case study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: One concussed individual with a cohort of healthy controls (n = 10) used for comparison. MAIN OUTCOME MEASURES: Center of pressure variability (linear-SD and nonlinear-multiscale entropy) was used to index postural sway preinjury and at periodic intervals following the concussion. RESULTS: The concussed individuals displayed reduced amounts of sway during the initial recovery phase that failed to returned to preinjury levels but reached the level of healthy controls at 1-month postinjury. The multiscale entropy analysis revealed increased center of pressure irregularity throughout recovery that persisted up to 1-month post injury. CONCLUSIONS: The findings identified subtle, persistent postural control impairments revealed through the nonlinear analysis of center of pressure and supports the notion that the consequences of a concussion (ie, impaired postural control) need to be considered beyond the resolution of behavioral symptoms.

Application of a Novel Mass Spectral Data Acquisition Approach to Lipidomic Analysis of Liver Extracts from Sitaxentan-Treated Liver-Humanized PXB Mice.

The application of a data-independent acquisition (DIA) method ("SONAR") that employs a rapidly scanning quadrupole is described for the lipidomic analysis of complex biological extracts. Using this approach, the MS acquisition window can be varied between 1 and 25 Da, enabling the isolation of ions prior to their entering the collision cell. By rapidly scanning the resolving quadrupole window over a specified mass range, co-eluting precursor ions are transmitted sequentially into the collision cell, where collision energies are cycled between low and elevated levels to induce fragmentation. This method of data generation provides both precursor and fragment ion information at high specificity, allowing for greater accuracy of compound identification, whether using a database, spectral libraries, or comparison to authentic standards. The value of the approach in simplifying and "de-cluttering" the spectra of co-eluting lipids is shown with examples from lipidomic profiles obtained in investigations of the composition of organic extracts of livers obtained from SCID and chimeric liver-humanized mice administered under various experimental conditions.

Development of a rapid profiling method for the analysis of polar analytes in urine using HILIC-MS and ion mobility enabled HILIC-MS.

INTRODUCTION: As large scale metabolic phenotyping is increasingly employed in preclinical studies and in the investigation of human health and disease the current LC-MS/MS profiling methodologies adopted for large sample sets can result in lengthy analysis times, putting strain on available resources. As a result of these pressures rapid methods of untargeted analysis may have value where large numbers of samples require screening. OBJECTIVES: To develop, characterise and evaluate a rapid UHP-HILIC-MS-based method for the analysis of polar metabolites in rat urine and then extend the capabilities of this approach by the addition of IMS to the system. METHODS: A rapid untargeted HILIC LC-MS/MS profiling method for the analysis of small polar molecules has been developed. The 3.3 min separation used a Waters BEH amide (1 mm ID) analytical column on a Waters Synapt G2-Si Q-Tof enabled with ion mobility spectrometry (IMS). The methodology, was applied to the metabolic profiling of a series of rodent urine samples from vehicle-treated control rats and animals administered tienilic acid. The same separation was subsequently linked to IMS and MS to evaluate the benefits that IMS might provide for metabolome characterisation. RESULTS: The rapid HILIC-MS method was successfully applied to rapid analysis of rat urine and found, based on the data generated from the data acquired for the pooled quality control samples analysed at regular intervals throughout the analysis, to be robust. Peak area and retention times for the compounds detected in these samples showed good reproducibility across the batch. When used to profile the urine samples obtained from vehicle-dosed control and those administered tienilic acid the HILIC-MS method detected 3007 mass/retention time features. Analysis of the same samples using HILIC-IMS-MS enabled the detection of 6711 features. Provisional metabolite identification for a number of compounds was performed using the high collision energy MS/MS information compared against the Metlin MS/MS database and, in addition, both calculated and measured CCS values from an experimentally derived CCS database. CONCLUSION: A rapid metabolic profiling method for the analysis of polar metabolites has been developed. The method has the advantages of speed and both reducing sample and solvent consumption compared to conventional profiling methods. The addition of IMS added an additional dimension for feature detection and the identification of metabolites.

An enhanced recovery program in colorectal surgery is associated with decreased organ level rates of complications: a difference-in-differences analysis.

BACKGROUND: Perioperative care has lacked coordination and standardization. Enhanced recovery programs (ERPs) have been shown to decrease aggregate complications across surgical specialties. We hypothesize that the sustained implementation of an ERP will be associated with a decrease in a broad range of complications at the organ system level. STUDY DESIGN: Adult patients undergoing elective colorectal procedures between 1/2011 and 10/2016 were included. Patients were stratified based on exposure to a sustained ERP (7/2014-10/2016) after an 18-month wash-in period in a pre-post analysis. The primary outcome was 30-day complication rate by organ category as collected by National Surgical Quality Improvement Program (NSQIP) abstractors. Demographic and other patient level data were collected. Complication rates were compared using multivariable regression employing a differences-in-differences (DiD) approach using the national NSQIP PUF file to account for secular trends. RESULTS: A total of 1182 patients were included in this study, with 47% treated in an ERP. The two groups were similar in age, gender, race, BMI, comorbidity index, and procedure type. In a multivariable DiD analysis, significant reductions were seen in surgical site infection (OR 0.30; 95% CI 0.20-0.43), postoperative pulmonary complications (OR 0.46; 95% CI 0.24-0.90), transfusion (OR 0.27; 95% CI 0.15-0.51), urinary tract infections (OR 0.34; 95% CI 0.18-0.66), sepsis (OR 0.35; 95% CI 0.20-0.61), and cardiac complications (OR 0.10; 95% CI 0.01-0.84). A reduction in return to the operating room and 30-day readmission was also observed. Median length of stay (LOS) decreased from 5.2 to 3.5 days (p < 0.001). No significant changes occurred for acute kidney injury and hematologic complications. CONCLUSION: An ERP was associated with reduced complication rates across a wide range of organ categories and > 1.5-day reduction in LOS in a colorectal surgery population.

Evidence Review Conducted for the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology for Bariatric Surgery.

Enhanced recovery after surgery protocols for bariatric surgery are increasingly being implemented, and reports suggest that they may be associated with superior outcomes, reduced length of hospital stay, and cost savings. The Agency for Healthcare Research and Quality, in partnership with the American College of Surgeons and the Johns Hopkins Medicine Armstrong Institute for Patient Safety and Quality, has developed the Safety Program for Improving Surgical Care and Recovery. We have conducted an evidence review to select anesthetic interventions that positively influence outcomes and facilitate recovery after bariatric surgery. A literature search was performed for each intervention, and the highest levels of available evidence were considered. Anesthesiology-related interventions for pre- (carbohydrate loading/fasting, multimodal preanesthetic medications), intra- (standardized intraoperative pathway, regional anesthesia, opioid minimization and multimodal analgesia, protective ventilation strategy, fluid minimization), and postoperative (multimodal analgesia with opioid minimization) phases of care are included. We have summarized the best available evidence to recommend the anesthetic components of care for enhanced recovery after surgery for bariatric surgery. There is evidence in the literature, and from society guidelines, to support the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery goals for bariatric surgery.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Opioid Minimization in Opioid-Naïve Patients.

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

Segment Coordination Variability During Double Leg Bodyweight Squats at Different Tempos.

The aims of this study were twofold: 1) to examine lower extremity coordination during bodyweight squats performed at two different tempos, and 2) to establish a reliable measure of segment coordination variability. Eighteen subjects (10 F, 8 M) completed bodyweight squats at preferred (self-paced) and non-preferred (metronome-paced) tempos. A modified vector coding approach used kinematic data to compute absolute couplings patterns and coordination variability for three couplings (foot-shank, shank-thigh, thigh-trunk) in three planes of motion for the descent and ascent phases of a squat cycle. A coordination variability reliability equation was used to determine the number of squats needed for a reliable index of movement variability relative to total variability over 20 squats. Tempo did not significantly alter the absolute coordination patterns of any couplings. The reliability equation revealed that 5-9 squats were needed for a reliable coordination variability measure. Nine squats provided a reliable measure of coordination that is comparable to using 20 double leg squats in the calculation. Using nine squats ensures reliable calculations in the frontal, sagittal and transverse planes at preferred and non-preferred speeds. These results can be used to guide clinical evaluation of acceptable levels of movement variability during rehabilitation.

Ketorolac Use and Anastomotic Leak in Elective Colorectal Surgery: A Detailed Analysis.

BACKGROUND: Recent population-level analyses have linked ketorolac use to adverse outcomes. However, its use is also associated with decreased opioids and faster return of bowel function. OBJECTIVE: This study aims to assess the association between ketorolac and anastomotic leak. We hypothesize that receiving at least 1 dose of ketorolac will not be associated with anastomotic leak in elective colorectal surgery. DESIGN: This is a retrospective, observational cohort study of a prospectively collected data base. Anastomotic leak rates and other patient outcomes were adjusted for patient-level factors and then compared via a multivariable logistic regression. A secondary analysis assessed a dose-response association with anastomotic leak. SETTING: This study was conducted at a tertiary care colorectal surgery service. PATIENTS: Consecutive patients undergoing elective colorectal surgery with a nondiverted anastomosis were identified from 2012 to 2016. INTERVENTION: Exposure was defined as any administration of ketorolac during the perioperative time period. MAIN OUTCOME MEASURES: The primary outcome measured was anastomotic leak. RESULTS: A total of 877 patients met inclusion criteria. Of these, 479 (54.6%) were women, and the median age was 55 years. Overall, 566 (64.5%) patients were exposed to ketorolac. In the cohort, 27 (3.1%) patients experienced an anastomotic leak. In an unadjusted analysis, there was no association between ketorolac exposure and anastomotic leak (ketorolac: 3.1% vs no ketorolac: 3.3%; p = 0.84). This persisted in a multivariable model (OR, 0.98; 95% CI, 0.38-2.57; p = 0.98). Neither AKI (OR, 3.24; 95% CI, 0.51-20.6; p = 0.21), return to the operating room (OR, 1.07; 95% CI, 0.40-2.85; p = 0.88), nor readmission (OR, 1.03; 95% CI, 0.59-1.80; p = 0.93) was associated with ketorolac use. In a secondary analysis of patients receiving ketorolac, there was no association between total ketorolac dosing and anastomotic leak (OR, 0.99; 95% CI, 0.99-1.00; p = 0.20). LIMITATIONS: This study was a retrospective review, and there was a low incidence of anastomotic leak. CONCLUSION: Ketorolac exposure was associated with neither anastomotic leak nor other important postoperative outcomes. See Video Abstract at http://links.lww.com/DCR/A784.

Intensive Care Unit Enhanced Recovery Pathway for Patients Undergoing Orthotopic Liver Transplants Recipients: A Prospective, Observational Study.

BACKGROUND: Liver transplant recipients continue to have high perioperative resource utilization and prolonged length of stay despite improvements in perioperative care. Enhanced recovery pathways have been shown in other surgical populations to produce reductions in hospital resource utilization. METHODS: A prospective, observational study was performed to examine the effect of an enhanced recovery pathway for postoperative care after liver transplantation. Outcomes from patients undergoing liver transplantation from November 1, 2013, to October 31, 2014, managed by the pathway were compared to transplant recipients from the year before pathway implementation. Multivariable regression analysis was used to assess the association of the clinical pathway on clinical outcomes. RESULTS: The intervention and control groups included 141 and 106 patients, respectively. There were no demographic differences between the control and intervention group including no differences between the length of surgery and cold ischemic time. Median intensive care unit length of stay was reduced from 4.4 to 2.6 days (P < .001). The intervention group had a higher likelihood of earlier discharge (hazard ratio [95% CI], 2.01 [1.55-2.62]; P < .001), and a 69% and 65% lower odds of receiving a plasma (P < .001) or packed red blood cell (P < .001) transfusion. There was no significant effect on hospital mortality (P = .40), intensive care unit readmission rates (P = .75), or postoperative infections (urinary traction infections: P = .09; pneumonia: P = .27). CONCLUSIONS: An enhanced recovery pathway focused on milestone-based elements of intensive care unit management and predetermined management triggers including hemodynamic goals, fluid therapy, perioperative antibiotics, glycemic control, and standardized transfusion triggers led to reductions in intensive care unit length of stay without an increase in perioperative complications.

High-Speed Quantitative UPLC-MS Analysis of Multiple Amines in Human Plasma and Serum via Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate: Application to Acetaminophen-Induced Liver Failure.

A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 µL of sample, provides the reproducible and robust separation of 66 analytes in 7.5 min, including baseline resolution of isomers such as leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2 to 20 and 800 µM. Intra- and interday accuracy of between 0.05 and 15.6 and 0.78-13.7% and precision between 0.91 and 16.9% and 2.12-15.9% were obtained. A further 33 biogenic amines can be monitored in samples for relative changes in concentration rather than quantification. Application of the assay to samples derived from healthy controls and patients suffering from acetaminophen (APAP, paracetamol)-induced acute liver failure (ALF) showed significant differences in the amounts of aromatic and branched chain amino acids between the groups as well as a number of other analytes, including the novel observation of increased concentrations of sarcosine in ALF patients. The properties of the developed assay, including short analysis time, make it suitable for high-throughput targeted UPLC-ESI-MS/MS metabonomic analysis in clinical and epidemiological environments.