Mechanisms behind protein-protein interactions in a ß-lg-legumin co-precipitate.

Interactions between pea protein and whey protein isolates in co-precipitates and blends consist of a combination of disulphide bonds, hydrophobic and electrostatic interactions. The present study aims to clarify if the two proteins with free thiols, ß-lactoglobulin (ß-lg) and legumin, played a significant role for these interactions. This study used different reagents to modify the conditions of interactions: N-ethylmaleimide (NEM) was used to block reactive thiols, while NaCl and SDS were used to prevent electrostatic or hydrophobic interactions, respectively. The effects of treatments were studied on protein solubility, structure and stability. SDS had no effect, while NEM and NaCl both had great effect, especially in combination. The results showed that interactions of ß-lg and legumin in both co-precipitates and blends are a synergism of electrostatic interactions and disulphide bonds. Thus, ß-lg and legumin are the main proteins responsible for previously observed interactions in protein isolates of whey and pea.

Health-related quality of life, functional decline, and long-term mortality in older patients following hospitalisation due to COVID-19.

BACKGROUND: Older people are particularly vulnerable to severe COVID-19. Little is known about long-term consequences of COVID-19 on health-related quality of life (HR-QoL) and functional status in older people, and the impact of age in this context. We aimed to study age-related change in health-related quality of life, functional decline and mortality among older patients 6 months following hospitalisation due to COVID-19. METHODS: This was a cohort study including patients aged 60 years and older admitted to four general hospitals in South-Eastern Norway due to COVID-19, from March 1 up until July 1, 2020. Patients who were still alive were invited to attend a six-month follow-up. Change in HR-QoL and functional status compared to before the COVID-19 hospitalisation were assessed using the EuroQol 5-dimensional-5 levels questionnaire (EQ. 5D-5L). A change in visual analogue scale (VAS) score of 7 or more was considered clinically relevant. RESULTS: Out of 216 patients aged 60 years and older that were admitted to hospital due to COVID-19 during the study period, 171 were still alive 180 days after hospital admission, and 106 patients (62%) attended the six-month follow-up. Mean age was 74.3 years, 27 patients (26%) had experienced severe COVID-19. Fifty-seven participants (54%) reported a decrease in the EQ. 5D-5L VAS score after 6 months, with no significant difference between persons aged 75 years and older compared to younger. Seventy participants (66%) reported a negative change in any of the dimensions of the EQ. 5D-5L, with impaired ability to perform activities of daily life (35%), reduced mobility (33%) and having more pain or discomfort (33%) being the most commonly reported changes. Forty-six participants (43%) reported a negative change in cognitive function compared to before the COVID-19 hospitalisation. Six-month mortality was 21%, and increased with increasing age. CONCLUSIONS: More than half of the patients reported a negative change in HR-QoL 6 months following hospitalisation due to COVID-19, and one out of three experienced a persistently impaired mobility and ability to carry out activities of daily living. The results suggest awareness of long-term functional decline in older COVID-19 patients.

Morphological and molecular characterization of Cystoisospora laidlawi oocysts (Apicomplexa: Eimeriidae) in farmed American mink (Neovison vison) in Denmark.

From a longitudinal survey conducted on 30 Danish mink farms in 2016, 11.0% of faecal samples (456/4140) were positive for Cystoisospora laidlawi oocysts by microscopy, with 60% (189/315) of mink being positive at least once during the study period. Morphological analysis of sporulated oocysts identified Cystoisospora oocysts measuring 34.3 × 29.5 µm with an oocyst length/width (L/W) ratio of 1.2. The morphological features of the oocysts were identical to Isospora laidlawi previously morphological identified in farmed mink from Denmark and elsewhere. Phylogenetic analysis of 18S rDNA sequences (1221 bp) from three positive mink indicated that Cystoisospora from mink shared the highest genetic similarity to C. canis from a Canadian dog (99.6%). The phylogenetic analysis placed Cystoisospora from mink in a clade with other Cystoisospora isolates.

Health assessment of harbour porpoises (PHOCOENA PHOCOENA) from Baltic area of Denmark, Germany, Poland and Latvia.

Harbour porpoise (Phocoena phocoena), the only resident cetacean species of the Baltic Sea is formed of two subpopulations populations, occurring in the western Baltic, Belt Seas and Kattegat and the Baltic Proper, respectively. Harbour porpoises throughout these areas are exposed to a large number of human activities causing direct and indirect effects on individuals, that might also harm this species on a population level. From Latvia, Poland, Germany and Denmark 385 out of 1769 collected dead harbour porpoises were suitable for extensive necropsy. The animals were collected between 1990 and 2015 and were either by-caught or found dead on the coastline. Following necropsies, histopathological, microbiological, virological and parasitological investigations were conducted. Females and males were equally distributed among the 385 animals. Most animals from the different countries were juveniles between 3 months and 3 years old (varying between 46.5 and 100% of 385 animals per country). The respiratory tract had the highest number of morphological lesions, including lungworms in 25 to 58% and pneumonia in 21 to 58% of the investigated animals. Of those with pneumonia 8 to 33% were moderate or severe. The alimentary, hearing, and haematopoietic systems had inflammatory lesions and parasitic infections with limited health impact. 45.5 to 100% of the animals from the different countries were known by-caught individuals, of which 20 to 100% varying between countries had netmarks. Inflammatory lesions, especially in the respiratory tract were found in higher numbers when compared to control populations in areas with less human activities such as arctic waters. The high number of morphological changes in the respiratory tract and of bycatches especially among immature animals before reaching sexual maturity is of serious concern, as well as the low number of adult animals among the material. Data on health status and the causes of death are valuable for management. A next step in this regard will combine data from health and genetic investigations in order to detect differences between the two populations of the Baltic.

Responsiveness of different dynamic contrast-enhanced magnetic resonance imaging approaches: a post-hoc analysis of a randomized controlled trial of certolizumab pegol in rheumatoid arthritis.

Objective: The aim was to explore dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early marker of therapeutic response in patients with rheumatoid arthritis (RA) starting treatment with certolizumab pegol (CZP).Method: In 40 RA patients initiating CZP (27 patients) or 2 weeks of placebo (PCB) followed by CZP (13 patients), DCE-MRI of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was performed at weeks 0, 1, 2, 4, 8, and 16. Using semi-automated software, three methods for drawing volume regions of interest (ROIs) in MCP2-5 and PIP2-5 were applied: 'Standard' (slices: all; joints: MCP2-5 together and PIP2-5 together), 'Detailed' (slices: slices with high-quality visualization; joints: as Standard), and 'Single-joint' (slices: as Detailed; joints: each joint separately). The number of enhancing voxels (Nvoxel), initial rate of enhancement (IRE), and maximum enhancement (ME) were extracted and analysed for each method.Results: Nvoxel in MCP2-5, and IRE and ME in PIP2-5 decreased statistically significantly (Wilcoxon rank-sum test, p < 0.02-0.03) after 16 weeks of treatment for the Standard method. Nvoxel and ME decreased significantly more in the CZP group than in the PCB group after 1 week of treatment, but not at later time-points. There were no significant changes for DCE-MRI parameters for the Detailed and Single-joint methods.Conclusions: Certain DCE-MRI parameters detected decreased inflammation during CZP treatment in RA patients. Using specific criteria for ROIs, as in the Detailed and Single-joint methods, decreased the statistical power and could not show any changes over time.

Characterisation of footpad lesions in organic and conventional broilers.

Recent data suggest that organic broilers often score worse on footpad lesions than conventional broilers but also that the current scoring of organic broiler feet may be misleading. In order to characterise footpad lesions in organic broilers, this study assessed and compared footpad lesions in a sample of 2987 conventional and 3578 organic broiler feet obtained from a large Danish abattoir during summer and winter. The feet were scored according to two scoring systems: the modified Danish surveillance scoring system and a histopathology-based new scoring system specifically developed to target the ability to differentiate between broiler feet with hyperkeratosis and ulcers. For both systems, all broiler feet with visible lesions were cross-sectionally incised. Significant differences between the two production systems were found for both scoring systems (χ2 = 710; P < 0.001 and χ2 = 247; P < 0.001 for the new and the surveillance systems, respectively), showing that a larger proportion of the organic feet compared to conventional feet - summer and winter - exhibited signs of hyperkeratosis. In addition, a smaller fraction of the organic feet than of the conventional feet were given the outermost scores, that is, normal or ulcerated; 13.4% v. 25.3% broiler feet were given score 0 for organic v. conventional production systems, respectively (χ2 = 152; P < 0.001), and 18.4% v. 23.8% feet were given score 4 for organic v. conventional production systems, respectively (χ2 = 308; P < 0.001). Thus, the results suggest that surveillance scoring systems such as the one used in Denmark are useful for the examination of footpad lesions in broilers from both types of production systems. However, the results have also raised attention to a typical characteristic of the feet of organic broilers, that is, profound hyperkeratosis, which may underlie potential misclassifications in surveillance scoring systems like the one used in Denmark. Among the possible solutions to this challenge to the correctness and fairness of the scoring system are improved procedures (such as mandatory incision), training of technicians and calibration of results (especially for the organic footpads).

Clinical and echocardiographic predictors of embolism in infective endocarditis: systematic review and meta-analysis.

OBJECTIVES: Prediction of embolic events (EEs) in infective endocarditis (IE) could inform clinical decisions, such as surgical timing. We conducted a systematic review to more precisely define associations between risk factors and EEs. METHODS: We searched two bibliographic databases (1994-2018) for observational studies that reported EEs in IE patients and considered clinical, microbiological or echocardiographic risk factors. Studies that did not use Duke criteria or only investigated a subset of IE patients were excluded. Study quality was assessed using the Newcastle-Ottawa scale. A pooled risk ratio (RR) for each risk factor was estimated using random-effects models; statistical heterogeneity was estimated using I2. RESULTS: Of 3862 unique citations, 47 cohort studies (11 215 IE cases) were included; 54 risk factors were analysed in at least two studies, with nine studies reporting other individual factors. Most studies were of high methodological quality. Major predictors of EEs were intravenous drug use (RR 1.69, 95% CI 1.32-2.17; I2 = 46%), Staphylococcus aureus infection (RR 1.64, 95% CI 1.45-1.86, I2 = 32%), mitral valve vegetation (RR 1.24, 95% CI 1.11-1.37, I2 = 30%), and vegetation size >10 mm (RR 1.87, 95% CI 1.57-2.21, I2 = 48%). EE risk was also higher with human immunodeficiency virus, chronic liver disease, elevated C-reactive protein, Staphylococcus spp. infection, vegetation presence, and multiple, mobile or prosthetic mechanical valve vegetation, and lower with Streptococcus spp. infection. Most findings were unchanged in sensitivity analyses that removed studies with pulmonary EEs from the outcome. CONCLUSIONS: Given the serious consequences of embolism, surgical evaluation may be considered in patients with these risk factors.

Morphological and molecular characterisation of Eimeria vison-like oocysts (Apicomplexa:Eimeriidae) in farmed mink (Neovison vison) in Denmark.

A survey was conducted on 30 Danish mink farms from April to October 2016 to determine the prevalence and species of Eimeria in Danish farmed mink. In total, 2.6% of mink faecal samples (108/4140) were positive for Eimeria vison-like oocysts by microscopy, with 24.8% (78/315) of mink being positive at least once during the study period. Morphological analysis of sporulated oocysts (n = 20) identified Eimeria vison-like oocysts measuring 21.0 × 13.8 µm with a length/width (L/W) ratio of 1.5. Phylogenetic analysis of 18S rRNA sequences (1221 bp) from three positive mink indicated that Eimeria vison-like shared the highest genetic similarity to Eimeria sp. ex Apodemus agrarius from a Striped field mouse (A. agrarius) from the Czech Republic (99.6%). Analysis of a shorter region of 18S (531 bp) revealed that the E. vison-like genotype sequences grouped in the same clade and shared 97.7% similarity with E. furonis. At the cytochrome c oxidase subunit I (COI) locus, mink-derived sequences were not available from GenBank and phylogenetic analysis placed the novel E. vison-like in a clade with E. cf. ictidea (99.4% similarity) from a black footed ferret (Mustela nigripes) from Canada.

Genetic and biological characterization of a Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) causing significant clinical disease in the field.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the cause of severe reproductive and respiratory disease in swine worldwide. In Denmark, both PRRSV-1 and PRRSV-2 are circulating and approximately 35% of pig herds are seropositive for PRRSV. In November 2010, a pig herd in the Northern part of Denmark experienced an infection with PRRSV-2 with clinical signs that were much more severe than normally reported from current Danish PRRSV-2 affected herds. Due to the clinical observations of reproductive failure in sows and high mortality in piglets, it was speculated that a new, more pathogenic or vaccine evading PRRSV strain had emerged in Denmark. The overall aim of the present study was to perform a genetic and biological characterization of the virus isolated from the diseased herd. Complete genome sequencing of isolates from this herd revealed that although the case strain had some unique genetic features including a deduced 3 amino acid deletion, it was in overall very similar to the other PRRS-2 viruses circulating in Denmark. In an experimental trial in growing pigs, no overt clinical signs or pathology were observed following intranasal inoculation with the new virus isolate. Virus shedding, acute phase protein responses and serological responses were comparable to those seen after experimental challenge with a Danish PRRSV-2 reference strain isolated in 1997. Vaccination with a commercial modified live PRRSV-2 vaccine had a clear reducing effect on virus shedding, magnitude, and duration of viremia and viral load in the lungs. Overall, the results indicate that the severe disease observed in the field was contributed by additional factors in combination with the PRRS virus infection.

Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis.

OBJECTIVE: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated. RESULTS: The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions. CONCLUSIONS: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice.

Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage.

OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.

Quantification of bovine milk protein composition and coagulation properties using infrared spectroscopy and chemometrics: A result of collinearity among reference variables.

Predicting protein fractions and coagulation properties in bovine milk using Fourier transform infrared (FT-IR) measurements is desirable. However, such predictions may rely on correlations with total protein content. The aim of this study was to show how correlations between total protein content, protein fractions, and coagulation properties are responsible for the successful prediction of protein fractions and rennet-induced coagulation properties in milk samples. This study comprised 832 bovine milk samples from 2 breeds (426 Holstein and 406 Jersey). Holstein samples were collected from 20 Danish dairy herds from October to December 2009; Jersey samples were collected from 22 Danish dairy herds from February to April 2010. All samples were from conventional herds and taken while cows were housed. The results showed that κ-CN, αS1-CN, αS1-CN with 8 phosphorylated groups attached (αS1-CN 8P), and curd firming rate could be predicted from FT-IR measurements of the milk samples (with coefficients of determination between 0.66 and 0.71). However, the success of these FT-IR-based predictions was based on indirect relationships with total protein content. Hence, the FT-IR predictions relied on covariance structures with total protein content rather than absorption bands directly associated with the protein fractions and coagulation properties. If covariance structures between the protein fractions, coagulation properties, and total protein content used to calibrate partial least squares models were not conserved in future samples, these samples would show incorrect predictions of the protein fractions and coagulation properties. We demonstrated this using samples from 1 breed to calibrate and samples from the other breed to validate partial least squares models for ß-CN. The 2 breeds had different covariance structures between ß-CN and total protein content, and the validation samples yielded incorrect predictions. This finding may limit the usefulness of FT-IR-based predictions of protein fractions in milk recording, because indirect covariance structures in the calibration set must be valid for future samples, or future samples will show incorrect predictions.

Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Perioperative pain treatment often consist of combinations of non-opioid and opioid analgesics, 'multimodal analgesia', in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment. METHODS: Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24-h opioid consumption and incidence of serious adverse events (SAE). RESULTS: One hundred and thirty-two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24-h opioid consumption of 3.1 mg [0.5, 5.6] [corrected]. In the analysis of gabapentin as add-on analgesic to another non-opioid analgesic regimen found a mean reduction in 24-h morphine consumption of 1.2 mg [-0.3, 2.6; TSA-adjusted CI: -0.3, 2.6] in trials with low risk of bias. [corrected]. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 [0.91; 2.86; TSA-adjusted CI: 0.57, 4.57]. CONCLUSION: Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.

Post-operative serious adverse events in a mixed surgical population - a retrospective register study.

BACKGROUND: The number of surgical procedures is increasing, and knowledge of surgical risk factors, post-operative mortality and serious adverse events (SAE) is essential. The aim with our study was to determine the risk of a composite outcome of post-operative: death; myocardial infarction; pulmonary embolism; stroke; gastrointestinal bleeding; dialysis or reoperation. METHODS: Data of surgical procedures in the period from January 1, 2012 to June 30, 2012 were retrieved from the Danish Anaesthesia Database (DAD). Follow-up of all patients undergoing hip or knee replacement, abdominal or gynaecological surgery was conducted retrieving data from The Danish Civil Registration System and the National Patient Register. Total observation time was from January 1, 2012 to June 6, 2013. RESULTS: A total7449 adult patients were included in the final analysis. The risk of the composite outcome during a follow-up until 342 days after inclusion of the last patient was estimated to 8.3%, 95% Confidence Intervals (CI) (7.8-9.0), with a median observation time of 437 days (IQR 387-485, range 0-522). The risk of the composite outcome within 90- and 180-day follow-up of each patient was 4.8% (4.4-5.3) and 5.9% (5.4-6.5), respectively. Mortality within longest follow-up as well as 90 and 180 days post-operatively was 3.6% (3.1-4.0), 1.7% (1.4-2.0), and 2.2% (1.9-2.6), respectively. CONCLUSION: We found a risk of one or more events in the composite outcome within 342 days after inclusion of the last patients of 8.3% (7.8-9.0). The results are applicable in estimations of adequate sample sizes in future clinical trials investigating effects of interventions on SAEs.

Associations between psychological variables and pain in experimental pain models. A systematic review.

BACKGROUND: The association between pain and psychological characteristics has been widely debated. Thus, it remains unclear whether an individual's psychological profile influences a particular pain experience, or if previous pain experience contributes to a certain psychological profile. Translational studies performed in healthy volunteers may provide knowledge concerning psychological factors in healthy individuals as well as basic pain physiology. The aim of this review was to investigate whether psychological vulnerability or specific psychological variables in healthy volunteers are predictive of the level of pain following experimental pain models. METHODS: A systematic search on the databases, PubMed, Embase, Cochcrane library, and Clinicaltrials.gov was performed during September 2014. All trials investigating the association between psychological variables and experimental pain in healthy volunteers were considered for inclusion. RESULTS: Twenty-nine trials met the inclusion criteria, with a total of 2637 healthy volunteers. The included trials investigated a total of 45 different psychological tests and 27 different types of pain models. The retrieved trials did not present a sufficiently homogenous group to perform meta-analysis. The collected results were diverse. A total of 16 trials suggested that psychological factors may predict the level of pain, seven studies found divergent results, and six studies found no significant association between psychological variables and experimental pain. CONCLUSION: Psychological factors may have predictive value when investigating experimental pain. However, due to substantial heterogeneity and methodological shortcomings of the published literature, firm conclusions are not possible.

Parallel transmit excitation at 1.5 T based on the minimization of a driving function for device heating.

PURPOSE: To provide a rapid method to reduce the radiofrequency (RF) E-field coupling and consequent heating in long conductors in an interventional MRI (iMRI) setup. METHODS: A driving function for device heating (W) was defined as the integration of the E-field along the direction of the wire and calculated through a quasistatic approximation. Based on this function, the phases of four independently controlled transmit channels were dynamically changed in a 1.5 T MRI scanner. During the different excitation configurations, the RF induced heating in a nitinol wire immersed in a saline phantom was measured by fiber-optic temperature sensing. Additionally, a minimization of W as a function of phase and amplitude values of the different channels and constrained by the homogeneity of the RF excitation field (B1) over a region of interest was proposed and its results tested on the benchtop. To analyze the validity of the proposed method, using a model of the array and phantom setup tested in the scanner, RF fields and SAR maps were calculated through finite-difference time-domain (FDTD) simulations. In addition to phantom experiments, RF induced heating of an active guidewire inserted in a swine was also evaluated. RESULTS: In the phantom experiment, heating at the tip of the device was reduced by 92% when replacing the body coil by an optimized parallel transmit excitation with same nominal flip angle. In the benchtop, up to 90% heating reduction was measured when implementing the constrained minimization algorithm with the additional degree of freedom given by independent amplitude control. The computation of the optimum phase and amplitude values was executed in just 12 s using a standard CPU. The results of the FDTD simulations showed similar trend of the local SAR at the tip of the wire and measured temperature as well as to a quadratic function of W, confirming the validity of the quasistatic approach for the presented problem at 64 MHz. Imaging and heating reduction of the guidewire were successfully performed in vivo with the proposed hardware and phase control. CONCLUSIONS: Phantom and in vivo data demonstrated that additional degrees of freedom in a parallel transmission system can be used to control RF induced heating in long conductors. A novel constrained optimization approach to reduce device heating was also presented that can be run in just few seconds and therefore could be added to an iMRI protocol to improve RF safety.

Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.

Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.

The analgesic effect of wound infiltration with local anaesthetics after breast surgery: a qualitative systematic review.

BACKGROUND: Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post-operative pain after breast surgery. METHODS: A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery. The analgesic effect was evaluated in a qualitative analysis by assessment of significant difference between groups (P < 0.05) in pain scores and supplemental analgesic consumption. RESULTS: Ten trials including 699 patients were included in the final analysis. Three trials investigated mastectomy, four trials partial or segmental mastectomy, and three trials breast reduction, excision of benign lump and unspecified breast surgery, respectively. Six trials demonstrated a small and short-lasting, but statistically significant reduction of post-operative pain scores, and four trials observed a statistically significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. CONCLUSION: Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild to moderate, and other non-invasive analgesic methods may be preferable in this surgical population.