Bioanalytical development and validation of liquid chromatographic–tandem mass spectrometric methods for the quantification of total and free cefazolin in human plasma and cord blood

AbstractObjectivesCefazolin is a commonly prescribed β-lactam antibiotic for prophylaxis against skin infections following surgery, including caesarean sections. Assessment of maternal and neonatal exposure is important for correlating drug concentrations to clinical outcomes. Thus, bioanalytical methods for the quantification of both total and free cefazolin in maternal plasma and cord blood can assist in the comprehensive evaluation of cefazolin exposure.Design and methodsSpecimen preparation for the measurement of total cefazolin was performed via protein precipitation with acetonitrile containing the internal standard cloxacillin. Ultrafiltration was used to isolate free cefazolin. Processed samples were analyzed on a Prelude SPLC system coupled to a TSQ triple quadrupole Vantage mass spectrometer. Methods were validated following FDA bioanalytical guidelines.ResultsThe analytical measuring ranges of these methods were 0.48–480µg/mL and 0.048–48µg/mL for total and free drug, respectively. Calibration curves were generated using 1/x2 weighted linear regression analysis. Total cefazolin demonstrated inter- and intra-assay precision of ≤20% at the LLOQ and ≤11.2% at other levels. Free cefazolin demonstrated inter- and intra-assay precision of ≤18.5% at the LLOQ and ≤12.6% at other levels, respectively. Accuracy (%DEV), carryover, matrix effects, recovery and stability studies were also acceptable based on FDA recommendations. Furthermore, it was demonstrated that samples prepared in cord blood can be accurately quantified from an adult plasma calibration curve, with recoveries ≤9.1% DIF and ≤11.9% DIF for total and free cefazolin, respectively.ConclusionsThe described LC–MS/MS methods allow for the measurement of total and free cefazolin in both plasma and cord blood

Many Roads to Synchrony: Natural Time Scales and Their Algorithms

We consider two important time scales---the Markov and cryptic orders---that monitor how an observer synchronizes to a finitary stochastic process. We show how to compute these orders exactly and that they are most efficiently calculated from the epsilon-machine, a process's minimal unifilar model. Surprisingly, though the Markov order is a basic concept from stochastic process theory, it is not a probabilistic property of a process. Rather, it is a topological property and, moreover, it is not computable from any finite-state model other than the epsilon-machine. Via an exhaustive survey, we close by demonstrating that infinite Markov and infinite cryptic orders are a dominant feature in the space of finite-memory processes. We draw out the roles played in statistical mechanical spin systems by these two complementary length scales.Comment: 17 pages, 16 figures: http://cse.ucdavis.edu/~cmg/compmech/pubs/kro.htm. Santa Fe Institute Working Paper 10-11-02

Red Blood Cell Distribution Width (RDW) Predicts COVID-19 Severity: A Prospective, Observational Study from the Cincinnati SARS-CoV-2 Emergency Department Cohort

Since previous evidence has demonstrated that red blood cell distribution width (RDW) may be a useful prognostic parameter in many critical illnesses and infectious diseases, we investigated the utility of RDW for monitoring patients with coronavirus disease 2019 (COVID-19). The study population consisted of 49 COVID-19 patients, including 16 (32.6%) with severe illness, 12 (24.5%) with severe acute kidney injury (AKI), and 8 (16.3%) requiring renal replacement therapy (RRT). The predictive value of blood tests, performed during emergency department evaluation, was then addressed. A progressive increase of RDW was observed with advancing COVID-19 severity. The area under the curve (AUC) of RDW was 0.73 for predicting severe illness, 0.80 for severe AKI, and 0.83 for RRT, respectively. In multivariate analysis, elevated RDW was associated with 9-fold and 16-fold increased odds of severe COVID-19 and AKI, respectively. The results of this study suggest that RDW should be part of routine laboratory assessment and monitoring of COVID-19

Systematic Assessment of the Quality and Comprehensibility of YouTube Content on Ulnar Collateral Ligament Injury and Management

Background: Ulnar collateral ligament (UCL) reconstruction has received a unique level of attention in the press and social media. There has also been an increasing use of the internet by patients to seek medical information. Concern exists regarding the quality and comprehensibility of online information when used for patient education. Purpose: To evaluate the quality and comprehensibility of the most-viewed YouTube videos related to the diagnosis and management of UCL injuries. Based on our new evidence-based scoring rubrics, we hypothesized that the quality and comprehensibility of these videos would be poor. Study Design: Cross-sectional study. Methods: The YouTube platform was searched on September 7, 2021, with the terms “UCL injury,” “ulnar collateral ligament injury,” “UCL surgery,” “ulnar collateral ligament surgery,” and “Tommy John surgery,” and the 50 most-viewed videos from each search were compiled, yielding 250 videos. After removal of duplicates and application of exclusion criteria, the 100 most-viewed videos remained. Basic attributes, including duration of video and number of views, were recorded. Each video was then analyzed by 2 independent reviewers and evaluated for 4 key parameters (quality of diagnostic content [QAR-D], quality of treatment content [QAR-T], presence of inaccurate information, and comprehensibility) and graded on a novel scale from 1 to 4 (4 being the most appropriate for patient education). Results: The mean QAR-D was 4.83 ± 3.41 (fair quality), and the mean QAR-T was 2.76 ± 3.26 (poor quality). Physician-led educational videos had both the highest mean QAR-D (6.37) and the highest mean QAR-T (4.34). No correlation was observed between video quality and views/likes. A total of 12 videos included ≥1 inaccuracy. The mean comprehensibility score was 2.66 ± 1.12, with 39 videos falling below the acceptable comprehensibility threshold (score \u3c3). Conclusion: The overall quality of UCL injury–related YouTube content was low. In addition, the absence of correlation between video quality and views/likes suggests that patients are not preferentially utilizing the limited high-quality content that does exist on the YouTube platform. In addition, inaccurate videos were prevalent (12%), and almost half of all videos were deemed inappropriate for patient education in terms of comprehensibility, as defined by our comprehensibility parameter

Yeast cells can access distinct quiescent states

We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G0 state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity

Operative Time Less Than 1.5 Hours, Male Sex, Dependent Functional Status, Presence of Dyspnea, and Reoperations Within 30 days Are Independent Risk Factors for Readmission After ACLR

PURPOSE: The purposes of this study are to use a large, patient-centered database to describe the 30-day readmission rate and to identify predictive risk factors for readmission after elective isolated ACLR. METHODS: The National Surgical Quality Improvement Program Database was retrospectively queried for isolated ACLR procedures between 2011 and 2017. Current Procedural Terminology (CPT) codes were used to identify isolated ACLR patients. Those undergoing additional procedures such as meniscectomy or multi-ligamentous reconstruction were excluded. Readmissions were analyzed against demographic variables with bivariate analysis. Multivariate logistic regression was used to find independent risk factors for 30-day readmissions after ACLR. RESULTS: A total of 11,060 patients (37.2% female) were included with an average age of 32.2 ± 10.6 years and mean body mass index (BMI) of 27.9 ± 6.5 kg/m(2) (29.2% were \u3e30). The overall readmission rate was 0.59%. The most reported reason for readmission was infection 0.22 (24 out of 11,060). The following variables were associated with significantly higher readmission rates: male sex (P = .001), history of severe chronic obstructive pulmonary disease (COPD) (P = .025), cardiac comorbidity (P = .034), operative time \u3e1.5 hours (P \u3c.001), partially dependent functional health status (P = .002), high preoperative creatinine (P = .009), normal preoperative albumin (P = .020), hypertension (P = .034), and reoperations (P \u3c .001). Operative time \u3e1.5 hours, male sex, dependent functional status, the presence of dyspnea, and undergoing a reoperation were identified as independent risk factors for 30-day readmissions (P \u3c .05 for all). CONCLUSIONS: Isolated ACLR is associated with low 30-day readmission rates. Operative time \u3e1.5 hours, male sex, dependent functional status, the presence of dyspnea, and 30-day reoperations are independent risk factors for readmission that should be considered in patient selection and addressed with preoperative counseling. LEVEL OF EVIDENCE: Level III, retrospective cohort study