Search

A review with 93 references describing various 3D printing approaches that have been used to create microfluidic devices containing electrodes for electrochemical detection. The use of 3D printing to fabricate microfluidic devices is a rapidly growing area. One significant research area is how to detect analytes in the devices for quantitation purposes. This review article is focused on methods used to integrate electrodes into the devices for electrochemical detection. The review is organized in terms of the methodology for integrating the electrode within the device. This includes (1) external coupling of traditional electrode materials with 3D printed devices; (2) printing conductive electrode materials as part of device printing; and (3) integrating traditional electrodes into the device as part of the print process. Example applications are given and some future directions are also outlined.

Aims: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, β-adrenoceptor (β-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant β 2 -AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD)., Methods: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, β 2 -AR agonist clenbuterol (20-160 μg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a β-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral β 2 -AR responses., Results: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 μg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 μg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of β 2 -agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol., Conclusions: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful β 2 -AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF., (© 2024 British Pharmacological Society.)

Abstract: The prior articles in this series have focused on measuring cost and quality in acute care surgery. This third article in the series explains the current ways of defining value in acute care surgery, based on different stakeholders in the health care system-the patient, the health care organization, the payer and society. The heterogenous valuations of the different stakeholders require that the framework for determining high-value care in acute care surgery incorporates all viewpoints., Level of Evidence: Expert Opinion; Level V., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This work presents a heuristic for the selection of a time delay based on optimizing the global maximum of mutual information in orthonormal coordinates for embedding a dynamical system. This criterion is demonstrated to be more robust compared to methods that utilize a local minimum, as the global maximum is guaranteed to exist in the proposed coordinate system for any dynamical system. By contrast, methods using local minima can be ill-posed as a local minimum can be difficult to identify in the presence of noise or may simply not exist. The performance of the global maximum and local minimum methods are compared in the context of causality detection using convergent cross mapping using both a noisy Lorenz system and experimental data from an oscillating plasma source. The proposed heuristic for time lag selection is shown to be more consistent in the presence of noise and closer to an optimal uniform time lag selection.

This paper describes the use of PolyJet 3D printing to fabricate microchip electrophoresis devices with integrated microwire electrodes for amperometric detection. The fabrication process involves 3D printing of two separate pieces, a channel layer and an electrode layer. The channel layer is created by 3D printing on a pre-fabricated mold with a T-intersection. For the electrode layer, a stencil design is printed directly on the printing tray and covered with a piece of transparent glass. Microwire electrodes are adhered over the glass piece (guided by underlaying stencil) and a CAD design of the electrode layer is then printed on top of the microwire electrode. After delamination from the glass after printing, the microwire is embedded in the printed piece, with the stencil design ensuring that alignment and positioning of the electrode is reproducible for each print. After a thermal bonding step between the channel layer and electrode layer, a complete electrophoresis device with integrated microelectrodes for amperometric detection results. It is shown that this approach enables different microwire electrodes (gold or platinum) and sizes (100 or 50 µm) to be integrated in an end-channel configuration with no gap between the electrode and the separation channel. These devices were used to separate a mixture of catecholamines and the effect of separation voltage on the potential voltage applied on the working electrode was also investigated. In addition, the effect of electrode size on the number of theoretical plates and limit of detection was studied. Finally, a device that contains different channel heights and a detection electrode was 3D-printed to integrate continuous flow sampling with microchip electrophoresis and amperometric detection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from 6 cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA), fascicle length, etc. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in 7 and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle's moment arm, PCSA, and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibers (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion., Competing Interests: Competing interests The authors declare no competing interests.

Abstract: Acute care surgery (ACS) patients are frequently faced with significant long-term recovery and financial implications that extend far beyond their hospitalization. While major injury and emergency general surgery (EGS) emergencies are often viewed solely as acute moments of crisis, the impact on patients can be lifelong. Financial outcomes after major injury or emergency surgery have only begun to be understood. The Healthcare Economics Committee from the American Association for the Surgery of Trauma previously published a conceptual overview of financial toxicity in ACS, highlighting the association between financial outcomes and long-term physical recovery. The aims of second-phase financial toxicity review by the Healthcare Economics Committee of the American Association for the Surgery of Trauma are to (1) understand the unique impact of financial toxicity on ACS patients; (2) delineate the current limitations surrounding measurement domains of financial toxicity in ACS; (3) explore the "when, what and how" of optimally capturing financial outcomes in ACS; and (4) delineate next steps for integration of these financial metrics in our long-term patient outcomes. As acute care surgeons, our patients' recovery is often contingent on equal parts physical, emotional, and financial recovery. The ACS community has an opportunity to impact long-term patient outcomes and well-being far beyond clinical recovery., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current data on tranexamic acid (TXA) supports early administration for severe hemorrhagic shock. Administration by EMS has been facilitated by developing protocols and standing orders informed by these data. In this study, patterns of TXA use by EMS agencies serving a large level 1 trauma center were examined. We hypothesized that current widespread TXA use often includes administration outside of data-driven indications., Methods: The trauma registry at a level 1 trauma center was queried for patients who received TXA. To determine the practice patterns and appropriateness of administration of TXA, patients' physiologic state in the prehospital environment based on EMS records, physiologic state on arrival to hospital, and interventions performed in both settings were examined. Over 20 separately managed EMS systems that administer TXA transport patients to this trauma center, allowing for a broad survey of practices., Results: From 2016 to 2021 1089 patients received TXA, 406 (37.3%) having treatment initiated by EMS services. Of these, the average prehospital systolic blood pressure (SBP) was 108.2 mmHg and initial ED SBP was 107.8 mmHg. Only 58.4% of these patients received blood transfusion after arrival to this trauma center. Compliance with standard indications was low with only 14.6% of administrations meeting any data-driven SBP indication. Similar levels of compliance were seen across high volume EMS services., Discussion: Tranexamic acid use has become common in trauma and has been adopted by many EMS systems. These results indicate TXA in the prehospital setting is over-used as administration is not being limited to indications that have shown benefit in prior data., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population., Methods: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days., Results: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups., Conclusion: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 American Association for the Surgery of Trauma.)

Purpose: Pulse Decomposition Analysis (PDA) uses integration of the systolic area of a distally transmitted aortic pulse as well as arterial stiffness estimates to compute cardiac output. We sought to assess agreement of cardiac output (CO) estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CCO) and a wireless, wearable noninvasive device, (Vitalstream, Caretaker Medical, Charlottesville, VA), that utilizes the Pulse Decomposition Analysis (CO-PDA) method in postoperative cardiac surgery patients in the intensive care unit., Methods: CO-CCO measurements were compared with post processed CO-PDA measurements in prospectively enrolled adult cardiac surgical intensive care unit patients. Uncalibrated CO-PDA values were compared for accuracy with CO-CCO via a Bland-Altman analysis considering repeated measurements and a concordance analysis with a 10% exclusion zone., Results: 259.7 h of monitoring data from 41 patients matching 15,583 data points were analyzed. Mean CO-CCO was 5.55 L/min, while mean values for the CO-PDA were 5.73 L/min (mean of differences +- SD 0.79 ± 1.11 L/min; limits of agreement - 1.43 to 3.01 L/min), with a percentage error of 37.5%. CO-CCO correlation with CO-PDA was moderate (0.54) and concordance was 0.83., Conclusion: Compared with the CO-CCO Swan-Ganz, cardiac output measurements obtained using the CO-PDA were not interchangeable when using a 30% threshold. These preliminary results were within the 45% limits for minimally invasive devices, and pending further robust trials, the CO-PDA offers a noninvasive, wireless solution to complement and extend hemodynamic monitoring within and outside the ICU., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Noradrenergic signaling declines in Parkinson's disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that β-acting drugs slow PD progression., Objective: The primary objective was to compare the safety and effects of 3 β-adrenoceptor (β-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of β-AR acting drugs in HVs and PD-patients., Methods: In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20μg on Day 1, 40μg on Day 2, 80μg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests., Results: Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral β2-AR effects were observed with clenbuterol., Conclusions: This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS.

Adrenoceptors (ARs) throughout the brain are stimulated by noradrenaline originating mostly from neurons of the locus coeruleus, a brainstem nucleus that is ostensibly the earliest to show detectable pathology in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The α 1 -AR, α 2 -AR, and β-AR subtypes expressed in target brain regions and on a range of cell populations define the physiological responses to noradrenaline, which includes activation of cognitive function in addition to modulation of neurometabolism, cerebral blood flow, and neuroinflammation. As these heterocellular functions are critical for maintaining brain homeostasis and neuronal health, combating the loss of noradrenergic tone from locus coeruleus degeneration may therefore be an effective treatment for both cognitive symptoms and disease modification in neurodegenerative indications. Two pharmacologic approaches are receiving attention in recent clinical studies: preserving noradrenaline levels (e.g., via reuptake inhibition) and direct activation of target adrenoceptors. Here, we review the expression and role of adrenoceptors in the brain, the preclinical studies which demonstrate that adrenergic stimulation can support cognitive function and cerebral health by reversing the effects of noradrenaline depletion, and the human data provided by pharmacoepidemiologic analyses and clinical trials which together identify adrenoceptors as promising targets for the treatment of neurodegenerative disease., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Abstract: Gains in inpatient survival over the last five decades have shifted the burden of major injuries and surgical emergencies from the acute phase to their long-term sequelae. More attention has been placed on evaluation and optimization of long-term physical and mental health; however, the impact of major injuries and surgical emergencies on long-term financial well-being remains a critical blind spot for clinicians and researchers. The concept of financial toxicity encompasses both the objective financial consequences of illness and medical care as well as patients' subjective financial concerns. In this review, representatives of the Healthcare Economics Committee from the American Association for the Surgery of Trauma (1) provide a conceptual overview of financial toxicity after trauma or emergency surgery, (2) outline what is known regarding long-term economic outcomes among trauma and emergency surgery patients, (3) explore the bidirectional relationship between financial toxicity and long-term physical and mental health outcomes, (4) highlight policies and programs that may mitigate financial toxicity, and (5) identify the current knowledge gaps and critical next steps for clinicians and researchers engaged in this work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cirrhosis in trauma patients is an indicator of poor prognosis, but current trauma injury grading systems do not take into account liver dysfunction as a risk factor. Our objective was to construct a simple clinical mortality prediction model in cirrhotic trauma patients: Cirrhosis Outcomes Score in Trauma (COST)., Methods: Trauma patients with pre-existing cirrhosis or liver dysfunction who were admitted to our ACS Level I trauma center between 2013 and 2021 were reviewed. Patients with significant acute liver trauma (AAST Grade ≥ 3) or those that developed acute liver dysfunction while admitted were excluded. Demographics as well as ISS, MELD, complications, and mortality were evaluated. COST was defined as the sum of age, ISS, and MELD. Univariate and multivariable analysis was used to determine independent predictors of mortality. The area under the receiver operating curve (AUROC) was calculated to assess the ability of COST to predict mortality., Results: A total of 318 patients were analyzed of which the majority were males 214 (67.3%) who suffered blunt trauma 305 (95.9%). Mortality at 30-days, 60-days, and 90-days was 20.4%, 23.6%, and 25.5%, respectively. COST was associated with inpatient, 30-day, and 90-day mortality on regression analyses and the AUROC for COST predicting mortality at these respective time points was 0.810, 0.801, and 0.813., Conclusion: Current trauma injury grading systems do not take into account liver dysfunction as a risk factor. COST is highly predictive of mortality in cirrhotic trauma patients. The simplicity of the score makes it useful in guiding clinical care and in optimizing goals of care discussions. Future studies to validate this prediction model are required prior to clinical use., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to report., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold., Methods: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery., Conclusions: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients., Funding: The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK)., Trial Registration: EudraCT number: 2021-002816-30., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

We sought to assess agreement of cardiac output estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CTD) and a novel pulse wave analysis (PWA) method that performs an analysis of multiple beats of the arterial blood pressure waveform (CO-MBA) in post-operative cardiac surgery patients. PAC obtained CO-CTD measurements were compared with CO-MBA measurements from the Argos monitor (Retia Medical; Valhalla, NY, USA), in prospectively enrolled adult cardiac surgical intensive care unit patients. Agreement was assessed via Bland-Altman analysis. Subgroup analysis was performed on data segments identified as arrhythmia, or with low CO (less than 5 L/min). 927 hours of monitoring data from 79 patients was analyzed, of which 26 had arrhythmia. Mean CO-CTD was 5.29 ± 1.14 L/min (bias ± precision), whereas mean CO-MBA was 5.36 ± 1.33 L/min, (4.95 ± 0.80 L/min and 5.04 ± 1.07 L/min in the arrhythmia subgroup). Mean of differences was 0.04 ± 1.04 L/min with an error of 38.2%. In the arrhythmia subgroup, mean of differences was 0.14 ± 0.90 L/min with an error of 35.4%. In the low CO subgroup, mean of differences was 0.26 ± 0.89 L/min with an error of 40.4%. In adult patients after cardiac surgery, including those with low cardiac output and arrhythmia CO-MBA is not interchangeable with the continuous thermodilution method via a PAC, when using a 30% error threshold., (© 2022. The Author(s).)

Introduction: Blunt cerebrovascular injury (BCVI) is an increasingly detected pattern in trauma with significant morbidity, putting patients at risk for subsequent stoke. Complex screening protocols exist to determine who should undergo CT angiography of the neck (CTAN) to evaluate for BCVI. Once identified, stroke incidence may be reduced with appropriate treatment across grades. We hypothesize that an expanded and simplified method for identifying patients with clinical suspicion for BCVI based upon injury above the clavicle (ATC) will illustrate a previously undiagnosed cohort of patients., Methods: A single-institution retrospective review of adult (age ≥18 years) blunt trauma patients with BCVI from January 1, 2010 to December 31, 2019 was conducted at a tertiary academic medical center. Patients undergoing CTAN were divided into 2 groups based upon qualification by either the expanded Denver criteria or clinical evidence of any injury ATC., Results: A total of 219 patients were diagnosed with BCVI (25 566 blunt trauma admissions, .9% incidence). Seventeen patients (8%) who did not satisfy expanded Denver were diagnosed with BCVI by ATC, most commonly undergoing CTAN due to facial trauma (n = 8). There were no differences in distribution of carotid artery injuries (CAI) and vertebral artery injuries (VAI) in the expanded Denver criteria group compared to the ATC group., Conclusions: CTAN for blunt trauma with any injury ATC is an easy-to-use screening tool and may be seamlessly included with initial whole-body imaging.