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BackgroundThe COVID-19 pandemic has resulted in shortages of diagnostic tests, personal protective equipment, hospital beds, and other critical resources. ObjectiveWe sought to improve the management of scarce resources by leveraging electronic health record (EHR) functionality, computerized provider order entry, clinical decision support (CDS), and data analytics. MethodsDue to the complex eligibility criteria for COVID-19 tests and the EHR implementation–related challenges of ordering these tests, care providers have faced obstacles in selecting the appropriate test modality. As test choice is dependent upon specific patient criteria, we built a decision tree within the EHR to automate the test selection process by using a branching series of questions that linked clinical criteria to the appropriate SARS-CoV-2 test and triggered an EHR flag for patients who met our institutional persons under investigation criteria. ResultsThe percentage of tests that had to be canceled and reordered due to errors in selecting the correct testing modality was 3.8% (23/608) before CDS implementation and 1% (262/26,643) after CDS implementation (P

Kun-Chun Chiang,1 Sheng-Teng Huang,2 Ren-Chin Wu,3 Shih-Chiang Huang,3 Ta-Sen Yeh,4 Ming-Huang Chen,5 Jun-Te Hsu,4 Li-Wei Chen,6 Sheng-Fong Kuo,7 Ho-Yen Chueh,8 Horng-Heng Juang,9 Shuen-Iu Hung,10 Chun-Nan Yeh,4 Jong-Hwei S Pang11,12 1General Surgery Department, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, ROC; 2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan, ROC; 3Department of Anatomic Pathology, Chang Gung Memorial Hospital, Kwei-Shan, Chang Gung University, Taoyuan, Taiwan, ROC; 4General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Chang Gung University, Taoyuan, Taiwan, ROC; 5Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; 6Department of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, ROC; 7Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, ROC; 8Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; 9Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan, ROC; 10Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; 11Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan, ROC; 12Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkow, Taoyuan City, Taiwan, ROC Objective: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA.Materials and methods: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied.Results: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial–mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients.Conclusion: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment. Keywords: IFI27, cholangiocarcinoma, oncogene, angiogenesis, VEGF-A, metastasis, tumor growth, cell cycle

Patient satisfaction measures and the opioid epidemic have highlighted the need for effective perioperative pain management. Multimodal analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs), have been shown to maximize pain relief and reduce opioid consumption, but are also associated with potential perioperative bleeding risks.A multidisciplinary panel conducted a clinical appraisal of bleeding risks associated with perioperative NSAID use. The appraisal consisted of review and assessment of the current published evidence related to the statement "In procedures with high bleeding risk, NSAIDs should always be avoided perioperatively." We report the presented literature and proceedings of the subsequent panel discussion and national pilot survey results. The authors' assessment of the statement based on current evidence was compared to the attempted national survey data, which revealed a wide range of opinions reflecting the ongoing debate around this issue in a small number of respondents.The appraisal concluded that caution is warranted with respect to perioperative use of NSAIDs. However, summarily excluding NSAIDs from perioperative use based on potential bleeding risks would be imprudent. It is recommended that NSAID use be guided by known patient- and procedure-specific factors to minimize bleeding risks while providing effective pain relief.

Context Diabetes is a global health concern, and diet is a contributing factor to diabetes. Findings regarding the connection between nitrate, nitrite, and nitrosamine and diabetes risk are inconsistent. Objective The aim was to examine the effects of these dietary compounds on diabetes risk. Data Sources The data were sourced from PubMed, EMBASE, Scopus, and Web of Science until February 28, 2023. Studies that reported individual-level consumption of these compounds were included. Review articles or ecological studies were excluded. Data Extraction The number of events and total observations were recorded. Data Analysis The pooled odds ratio (OR) was calculated and displayed in a forest plot. Subgroup and sensitivity analyses were predefined. A dose–response meta-analysis was conducted to determine the exposure intervals that may increase the risk of disease. Six observational reports that met the inclusion criteria were included, involving 108 615 individuals. Participants in the highest quantile of nitrite intake had a greater risk of diabetes compared with those in the lowest quantile (OR, 1.61; 95% confidence interval [CI], 1.08–2.39; I2 = 74%, P = 0.02). Higher nitrosamine consumption tended to increase diabetes risk (OR, 1.52; 95% CI, 0.76–3.04; I2 = 76%; P = 0.24). The relationship was stronger for type 1 (OR, 1.79; 95% CI, 1.20–2.67; I2 = 58%; P < 0.01) than for type 2 diabetes (OR, 1.42; 95% CI, 0.86–2.37; I2 = 71%; P = 0.17). Additionally, nitrite consumption had a dose-dependent association with both phenotypes. No association was found between diabetes risk and high nitrate intake (OR, 1.01; 95% CI, 0.87–1.18; I2 = 28%; P = 0.87). Conclusion Attention should be paid to the consumption of nitrite-containing foods. Systematic Review Registration PROSPERO registration no. CRD42023394462 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394462). [ABSTRACT FROM AUTHOR]

ObjectiveOpioids represent an important analgesic option for physicians managing acute pain in surgical patients. Opioid management is not without its drawbacks, however, and current trends suggest that opioids might be overused in the United States. An expert panel was convened to conduct a clinical appraisal regarding the use of opioids in the perioperative setting.MethodsThe clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the statement "Opioids are not overused in the United States, even though opioid adjunct therapy achieves greater pain control with less risk." The authors' evaluation of this statement was also compared with the results of a national survey of surgeons and anesthesiologists in the United States.ResultsWe report the presented literature and proceedings of the panel discussion. The national survey revealed a wide range of opinions regarding opioid overuse in the United States. Current published evidence provides support for the efficacy of opioid therapy in surgical patients; however, it is not sufficient to conclude unequivocally that opioids are-or are not-overused in the management of acute surgical pain in the United States.ConclusionsOpioids remain a key component of multimodal perioperative analgesia, and strategic opioid use based on clinical considerations and patient-specific needs represents an opportunity to support improved postoperative outcomes and satisfaction. Future studies should focus on identifying optimal procedure-specific and patient-centered approaches to multimodal perioperative analgesia.

This report describes a preliminary study that investigated the potential implications of using reclaimed rubberized asphalt pavement (R-RAP) materials as partial binder and aggregate replacement in new conventional dense-graded asphalt concrete mixes, and using reclaimed conventional asphalt pavement (RAP) materials as partial binder and aggregate replacement in new gap-graded asphalt rubber mixes. The use of rubberized hot mix asphalt (RHMA) in pavements in California has been increasing since the early 1990s. As these RHMA layers reach the end of their design lives they are being milled off and replaced with new hot mix asphalt (HMA) or new RHMA. The millings are being added to RAP stockpiles, which in turn are reused in new conventional HMA. There is no published information or experience documenting whether the use of R-RAP influences mix performance. Although Caltrans currently does not permit the use of any RAP in asphalt rubber mixes, there is increasing interest in allowing it as binder replacement in gap-graded mixes in order to reduce the amount of virgin binder required. Laboratory test results indicate that adding R-RAP to dense-graded HMA could potentially yield some improvement in overall rutting performance, but it could also have a potentially overall negative effect on fatigue and low-temperature cracking performance. These findings are consistent with those from tests where conventional RAP was used. The degree of change in rutting and cracking resistance in the HMA mixes was dependent on the R-RAP source, with mixes containing millings only from RHMA layers performing slightly better than mixes containing both R-RAP and RAP. Based on these findings, there appears to be no reason or justification for separating R-RAP and RAP millings or maintaining separate stockpiles at asphalt plants. Test results from the gap-graded RHMA mixes containing RAP indicated that rutting performance is likely to improve, but that adding RAP could have a potentially overall negative effect on fatigue and low-temperature cracking performance, which would negate the benefits of selecting RHMA-G as an overlay to retard the rate of reflection cracking. Since only limited testing on asphalt rubber mixes containing RAP was undertaken in this study, further laboratory testing, followed by full-scale field testing in pilot projects or accelerated wheel load testing should be considered on a wider range of virgin binder, virgin aggregate, and RAP material sources to confirm the findings before any changes to current practice are considered.

* Context.--Biomedical terminologies such as Logical Observation Identifiers, Names, and Codes (LOINC) were developed to enable interoperability of health care data between disparate health information systems to improve patient outcomes, public health, and research activities. Objective.--To ascertain the utilization rate and accuracy of LOINC terminology mapping to 10 commonly ordered tests by participants of the College of American Pathologists (CAP) Proficiency Testing program. Design.--Questionnaires were sent to 1916 US and Canadian laboratories participating in the 2018 CAP coagulation (CGL) and/or cardiac markers (CRT) surveys requesting information on practice setting, instrument(s) and test method(s), and LOINC code selection and usage in the laboratory and electronic health records. Results.--Ninety of 1916 CGL and/or CRT participants (4.7%) responded to the questionnaire. Of the 275 LOINC codes reported, 54 (19.6%) were incorrect: 2 codes (59342 and 12345-1) (0.7%) did not exist in the LOINC database and the highest error rates were observed in the property (27 of 275, 9.8%), system (27 of 275, 9.8%), and component (22 of 275, 8.0%) LOINC axes. Errors in LOINC code selection included selection of the incorrect component (eg, activated clotting time instead of activated partial thromboplastin time); selection of panels that can never be used to obtain an individual analyte (eg, prothrombin time panel instead of international normalized ratio); and selection of an incorrect specimen type. Conclusions.--These findings of real-world LOINC code implementation across a spectrum of laboratory settings should raise concern about the reliability and utility of using LOINC for clinical research or to aggregate data. (Arch Pathol Lab Med. 2020;144:586-596; doi: 10.5858/arpa.2019-0276-OA), Few things are more essential to the practice of modern medicine than the contribution of laboratory testing. A total of 234 756 laboratories in the United States, as of 2014, [...]

In the United States, the Superpave Asphalt Binder Performance Grading (PG) system proposed by the Strategic Highway Research Program (SHRP) is the most common method used to characterize the performance-related properties of conventional and polymer-modified asphalt binders. Dynamic modulus (G*) and phase angle (δ) are the two main binder properties and they are measured using a dynamic shear rheometer (DSR) with parallel plate geometry and either a 1 mm or 2 mm gap between the plates. Since these Superpave parameters were developed for binders that do not contain additives or particulates, the California Department of Transportation (Caltrans) does not use them as asphalt rubber binder specification criteria. Instead, penetration and viscosity are used as acceptance of quality control; however, these parameters do not necessarily provide a satisfactory link between the measured binder properties and potential performance in the field over a range of operating temperatures. In California, current specifications require that crumb rubber particles used to produce asphalt rubber binder in the “wet process” must be smaller than 2.36 mm (i.e., 100 percent passing the #8 sieve), and typically these particles vary in size between 1 mm and 2 mm. As a consequence, when the parallel plate geometry is used to test this type of binder, the larger rubber particles can contact the plates; if this occurs, the rubber particle rheology can potentially dominate the results, which in turn may not be representative of the modified binder as a whole. To address this problem, a potentially more appropriate DSR testing protocol using concentric cylinder geometry was investigated in this study to explore an alternative means of determining the performance properties of asphalt rubber binders. In the first phase of the study, documented in this technical memorandum, a series of tests were undertaken to compare the two geometries and to assess which binder properties influence the results from the testing approaches. The interim results indicate that there is no significant difference between the concentric cylinder and parallel plate geometries in terms of the G*/sinδ after testing on a range of different binders and asphalt rubber binders with finer crumb rubber particle sizes (i.e.

As a first step toward the elucidation of the systems biology of the model organism Escherichia coli, it was our goal to mathematically model a metabolic system of intermediate complexity, namely the well studied end product-regulated pathways for the biosynthesis of the branched chain amino acids L-isoleucine, L-valine, and L-leucine. This has been accomplished with the use of kMech (Yang, C.-R., Shapiro, B. E., Mjolsness, E. D., and Hatfield, G. W. (2005) Bioinformatics 21, in press), a Cellerator (Shapiro, B. E., Levchenko, A., Meyerowitz, E. M., Wold, B. J., and Mjolsness, E. D. (2003) Bioinformatics 19, 677-678) language extension that describes a suite of enzyme reaction mechanisms. Each enzyme mechanism is parsed by kMech into a set of fundamental association-dissociation reactions that are translated by Cellerator into ordinary differential equations. These ordinary differential equations are numerically solved by Mathematica (TM). Any metabolic pathway can be simulated by stringing together appropriate kMech models and providing the physical and kinetic parameters for each enzyme in the pathway. Writing differential equations is not required. The mathematical model of branched chain amino acid biosynthesis in E. coli K12 presented here incorporates all of the forward and reverse enzyme reactions and regulatory circuits of the branched chain amino acid biosynthetic pathways, including single and multiple substrate (Ping Pong and Bi Bi) enzyme kinetic reactions, feedback inhibition ( allosteric, competitive, and non-competitive) mechanisms, the channeling of metabolic flow through isozymes, the channeling of metabolic flow via transamination reactions, and active transport mechanisms. This model simulates the results of experimental measurements.

Much evidence supports the view that hypoxic/ischemic injury is largely due to increased intracellular Ca concentration ([Ca](i)) resulting from 1) decreased intracellular pH (pH(i)), 2) stimulated Na/H exchange that increases Na uptake and thus intracellular Na (Na(i)), and 3) decreased Na gradient that decreases or reverses net Ca transport via Na/Ca exchange. The Na/H exchanger (NHE) is also stimulated by hypertonic solutions; however, hypertonic media may inhibit NHE's response to changes in pH(i) (Cala PM and Maldonado HM. J Gen Physiol 103: 1035-1054, 1994). Thus we tested the hypothesis that hypertonic perfusion attenuates acid-induced increases in Na(i) in myocardium and, thereby, decreases Ca(i) accumulation during hypoxia. Rabbit hearts were Langendorff perfused with HEPES-buffered Krebs-Henseleit solution equilibrated with 100% O(2) or 100% N(2). Hypertonic perfusion began 5 min before hypoxia or normoxic acidification (NH(4)Cl washout). Na(i), [Ca](i), pH(i), and high-energy phosphates were measured by NMR. Control solutions were 295 mosM, and hypertonic solutions were adjusted to 305, 325, or 345 mosM by addition of NaCl or sucrose. During 60 min of hypoxia (295 mosM), Na(i) rose from 22+/-1 to 100+/-10 meq/kg dry wt while [Ca](i) rose from 347+/-11 to 1,306+/-89 nM. During hypertonic hypoxic perfusion (325 mosM), increases in Na(i) and [Ca](i) were reduced by 65 and 60%, respectively (P

BackgroundLiver dysfunction may be an early event or the end result of multiple organ dysfunction (MOD) in necrotizing pancreatitis. This study measured the early changes in hepatocellular ions and energetics associated with such conditions.MethodsTwenty-five rats, prepared with a 23Na and 31P double-tuned nuclear magnetic resonance surface coil secured over the dome of the liver, were randomized into 5 groups: control, 10 and 20 minutes of total inflow ischemia, pancreatitis induced by deoxycholic acid (DCA), and sham-DCA (saline injection). Dysprosium-TTHA3- solution was used to separate the intracellular and extracellular sodium peaks.ResultsIn rat liver, 20 minutes of total inflow occlusion caused irreversible depletion of high-energy phosphates. Changes at 2 hours after the onset of DCA-pancreatitis are compared with changes after 20 minutes of ischemia (mean +/- SEM). Although the DCA-pancreatitis animals did not become hypotensive until 1 hour after the induction of pancreatitis, the changes in hepatic intracellular ions and energetics began soon after such an insult. At 2 hours after the onset of pancreatitis, hepatocellular pHi and [NA+]i were 6.99 +/- 0.16 and 78.4 +/- mmol/L, respectively (P < .01, compared with sham animals). A similar pattern of changes in hepatic bioenergetics also occurred. After the onset of pancreatitis, the hepatic cytostolic phosphorylation potential decreased with time (y = 0.654 - 0.004t, where t is time in minutes and r2 = 0.967 and the rate of hepatic hydrolysis of adenosine triphosphate increased progressively (y = 0.702t + 91.363, where t is time in minutes and r2 = 0.969. These changes correlated well with the accumulated [Na]i.ConclusionsUnresuscitated necrotizing pancreatitis caused severe hepatocellular acidosis, profound sodium accumulation, and bioenergy depletion early in its course. These effects were as severe as those induced by total liver ischemia. Liver dysfunction may be an early, not terminal, event of MOD in necrotizing pancreatitis.

Background and Objectives: Providing red blood cell (RBC) transfusion to paediatric patients with a haemoglobin (Hb) level of <7 g/dL is the current best practice, but it is often difficult to ensure appropriateness of RBC transfusion on a health system level. Electronic health record (EHR) clinical decision support systems have been shown to be effective in encouraging providers to transfuse at appropriate Hb thresholds. We present our experience with an interruptive best practice alert (BPA) at a paediatric healthcare system. Materials and Methods: An interruptive BPA requiring physician response was implemented in our EHR (Epic Systems Corp., Verona, WI, USA) in 2018 based on Hb thresholds for inpatients. The threshold was initially <8 g/dL and later changed to <7 g/dL in 2019. We assessed total activations, number of RBC transfusions and hospital metrics through 2022 compared to the 2 years prior to implementation. Results: The BPA activated 6956 times over 4 years, slightly less than 5/day, and the success rate, with no RBC transfusions within 24 h of order attempt, was 14.5% (1012/6956). There was a downward trend in the number of total RBC transfusions and RBC transfusions per admission after implementation, non‐significant (p = 0.41 and p = >0.99). The annual case mix index was similar over the years evaluated. The estimated cost savings based on acquisition costs for RBC units were 213,822 USD or about $51,891 per year. Conclusion: BPA implementation led to sustained change in RBC transfusion towards best practice, and there were long‐term savings in RBC expenditure. [ABSTRACT FROM AUTHOR]