Search

Background: Blood loss during burn excisional surgery remains an important factor as it is associated with significant comorbidity, mortality and longer length of stay. Blood loss is, among others, influenced by length of surgery, burn size, excision size and age. Most literature available is aimed at large burns and little research is available for small burns. Therefore, the goal of this study is to investigate blood loss and develop a prediction model to identify patient at risk for blood loss during burn excisional surgery ≤ 10% body surface area. Study design and methods: This retrospective study included adult patients who underwent burn excisional surgery of ≤ 10% body surface area in the period 2013–2018. Duplicates, patients with missing data and delayed surgeries were excluded. Primary outcome was blood loss. A prediction model for per-operative blood loss (>250 ml) was built using a multivariable logistic regression analysis with stepwise backward elimination. Discriminative ability was assessed by the area under the ROC-curve in conjunction with optimism and calibration. Results: In total 269 patients were included for analysis. Median blood loss was 50 ml (0−150) / % body surface area (BSA) excised and 0.28 (0–0.81) ml / cm2. Median burn size was 4% BSA and median excision size was 2% BSA. Blood loss of> 250 ml was present in 39% of patients. The model can predict blood loss> 250 ml based on %BSA excised, length of surgery and ASA-score with an AUC of 0.922 (95% CI 0.883 – 0.949) and an AUC after optimism correction of 0.915. The calibration curve showed an intercept of 0.0 (95% CI −0.36 to 0.36) with a slope of 1.0 (95% CI 0.78–1.22). Conclusion: Median blood loss during burn excisional surgery of ≤ 10% BSA is 50 ml / % BSA excised and 0.28 ml / cm2 excised. However, a substantial part of patients is at risk for higher blood loss. The prediction model can predict P(blood loss>250 ml) with an AUC of 0.922, based on expected length of surgery, ASA-score and size of excision. The model can be used to identify patients at risk for significant blood loss (>250 ml).

In supersonic-combustion ramjets (scramjets), fuel is injected, which should mix rapidly with the supersonic crossflow to minimize the length of the scramjet. Tandem dual-jet injection has shown improved mixing performance over single-jet injection. However, experiments on tandem dual-jet injection have not addressed the jet shear layer, in which the mixing occurs, yet. The present study investigates the jet shear layer, as well as the bow shocks in front of the jets, in a continuous air-indraft supersonic wind tunnel at Mach number 1.55. A schlieren setup has been used for visualizing the flow features. A largely automated algorithm for processing schlieren images has been developed to determine the location of the upper boundary of the jet shear layer. The penetration of the jet is studied as a function of 1) J, the ratio of the momentum of the jet and that of the crossflow, and 2) the dimensionless distance S between the dual-jets. An empirical similarity relation has been established for the time-averaged location of the jet upper shear layer as function of J and S, covering the investigated conditions (J ∈ 2.8;3.8;4.8, S ∈ 0∶9.87). This empirical similarity relation provides Sopt, the spacing for maximal penetration of the jets as function of J.

Patients with extensive and complex wounds due to Necrotizing Soft-Tissue Infections (NSTI) may be referred to hospitals with a burn centre. This study describes the characteristics, outcomes, as well as diagnostic challenges of these patients. Patients admitted to three burn centres for the treatment of NSTI in a 5-year period were included. Eighty patients (median age 54 years, 60% male) were identified, of whom 30 (38%) were referred by other centres, usually after survival of the initial septic phase. Those referred from other centres, compared to those primarily admitted to the study hospital, were more likely to have group A streptococcal involvement (62% versus 35%, p=0.02), larger wounds (median 7% versus 2% total body surface area, p

Abstract The experimental identification of the transition region and the different flow structures inside the boundary layer is still a challenge. For the first time, this research uses the remote microphone probe technique to experimentally evaluate the boundary layer development, the transition process, and the type of flow structures. The remote microphone probe technique is an effective and accurate experimental method to measure wall-pressure fluctuations. The development of the boundary layer was evaluated under natural and forced transition for different inflow velocities and angles of attack. Results of the wall-pressure spectrum, spanwise coherence at different chord positions, and the spanwise correlation length close to the trailing edge are presented. Furthermore, boundary layer and far-field noise measurements at several conditions are also shown. This paper shows the growth of the turbulent structures that contain most of the turbulent energy along the airfoil chord. Further, it is demonstrated that the spanwise correlation length increases with the inflow velocity. Results for the no forced transition cases form a complete database to determine the different transition stages, which were linked with different components of the wall-pressure spectra. The primary and secondary instability mechanisms leading the transition process appear in the wall-pressure spectrum as peaks and a hump, respectively. The two- and three-dimensional nature of the boundary layer structures is also discussed by analyzing the spanwise coherence. Finally, it is shown that when two-dimensional structures reach the airfoil trailing edge, a feedback loop between the acoustic waves at the airfoil trailing edge and a point upstream in the airfoil surface is generated. This feedback loop influences the wall-pressure fluctuations along the entire airfoil chord. Graphical abstract

Schistosomes can survive in mammalian hosts for many years, and this is facilitated by released parasite products that modulate the host’s immune system. Many of these products are glycosylated and interact with host cells via C-type lectin receptors (CLRs). We previously reported on specific fucose-containing glycans present on extracellular vesicles (EVs) released by schistosomula, the early juvenile life stage of the schistosome, and the interaction of these EVs with the C-type lectin receptor Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN or CD209). EVs are membrane vesicles with a size range between 30–1,000 nm that play a role in intercellular and interspecies communication. Here, we studied the glycosylation of EVs released by the adult schistosome worms. Mass spectrometric analysis showed that GalNAcβ1–4GlcNAc (LacDiNAc or LDN) containing N-glycans were the dominant glycan type present on adult worm EVs. Using glycan-specific antibodies, we confirmed that EVs from adult worms were predominantly associated with LDN, while schistosomula EVs displayed a highly fucosylated glycan profile. In contrast to schistosomula EV that bind to DC-SIGN, adult worm EVs are recognized by macrophage galactose-type lectin (MGL or CD301), and not by DC-SIGN, on CLR expressing cell lines. The different glycosylation profiles of adult worm- and schistosomula-derived EVs match with the characteristic glycan profiles of the corresponding life stages and support their distinct roles in schistosome life-stage specific interactions with the host.

BackgroundThe WHO 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production. Here we focus on defined schistosome glycan antigens.MethodsTarget identification was performed by assessing antibody responses in well characterized cross-sectional and cohort sample sets (n=366 individuals) on tailor-made antigen microarrays. IgM and IgG binding to candidate diagnostic targets was measured for serum/plasma samples from: controlled human schistosome infection model (CSI), schistosome infected travellers, soil-transmitted helminth infected and non-infected individuals.FindingsWe found that antibodies to circulating anodic antigen (CAA) identify schistosome infection with high sensitivity (IgM≥100%, IgG≥97%) and specificity (IgM≥93%, IgG≥97%) in the test samples. Infection dose affected timing of anti-CAA antibody isotype switch. Furthermore, we demonstrate the presence of shared and non-specific glycan epitopes in crude schistosome cercarial and egg antigen preparations. Many non-specific glycan epitopes contained in crude antigen mixes are responsible for a large proportion of false schistosomiasis positives in standard serological assays.InterpretationCAA is target for development of highly sensitive and specific tools for schistosomiasis serology with use cases for travellers and surveillance in near and post-elimination settings as well as emerging transmission zones.FundingGlobal Health Innovative Technology Fund (GHIT), HIC-Vac, Leiden University Medical Center (LUMC)

Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode Brugia malayi and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing Brugia malayi glycans with plasma from uninfected individuals and from individuals infected with Loa loa, Onchocerca volvulus, Mansonella perstans and Wuchereria bancrofti, four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from Onchocerca volvulus and Mansonella perstans infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of Brugia malayi infected individuals. For these infection groups, Brugia malayi, Onchocerca volvulus and Mansonella perstans, we further studied the different IgG subclasses to Brugia malayi glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in Brugia malayi infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of Brugia malayi glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.

BackgroundSeveral studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias.MethodsProspective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. [18F]FDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of [18F]FDG-PET/CT was modeled with a Cox proportional hazards model using [18F]FDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of [18F]FDG-PET/CT in patients with high risk of metastatic infection.ResultsOf 476 patients, 178 (37%) underwent [18F]FDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval [CI]: .34–.74) in patients that underwent [18F]FDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68–1.48). Likewise, after correction for immortal time bias, [18F]FDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 [95% CI .77–2.21]), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63–1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 [95% CI .67–2.28]).ConclusionsAfter adjustment for immortal time bias [18F]FDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB.

Objective To compare the effectiveness of five versus seven days of nitrofurantoin treatment for urinary tract infection (UTI) in diabetic women. Methods Data were collected retrospectively from Dutch general practitioners between 2013 and 2020. Nitrofurantoin prescriptions with a duration of five (5DN) or seven days (7DN) in women with diabetes were included. Inverse propensity weighting (IPW) was performed to calculate adjusted risk differences (RD) for treatment failure within 28 days. Secondary outcomes were 14-day treatment failure, severe treatment failure, and 28-day treatment failure in defined risk groups. Results Nitrofurantoin was prescribed in 6866 episodes, 3247 (47,3%) episodes with 5DN and 3619 (52,7%) episodes with 7DN. Patients in the 7DN group had more co-morbidities, more diabetes-related complications and were more insulin-dependent. There were 517/3247 (15.9%) failures in the 5DN group versus 520/3619 (14.4%) in the 7DN group. The adjusted RD for failure within 28 days was 1.4% (95% CI -0.6 to 3.4). Conclusion We found no clinically significant difference in treatment failure in diabetic women with UTI treated either five or seven days with nitrofurantoin within 28 days. A 5-day treatment should be considered to reduce cumulative nitrofurantoin exposure in DM patients.

Postendodontic periapical fibrous scars (PFScs) comprise a type of radiolucent healing that is frequently misinterpreted as a pathological lesion. A combined clinical, radiologic, and histologic correlation is essential for a reliable diagnosis. This report presents a case of a patient with a long-term persistent asymptomatic postendodontic radiolucency that was misdiagnosed as endodontic failure and referred for endodontic retreatment and periapical surgery. To reach a definitive diagnosis, a core bone biopsy needle (CBBn) technique was performed on the area of the radiolucency. The material obtained was processed for histologic analysis and the lesion was determined to be a PFSc. In conclusion, the use of a CBBn before any invasive treatment allowed the clinician to distinguish between PFSc and other persisting pathosis, such as periapical granuloma or cystic lesions.

Summary Background Adults hospitalised to a non-intensive care unit (ICU) ward with moderately severe community-acquired pneumonia are frequently treated with broad-spectrum antibiotics, despite Dutch guidelines recommending narrow-spectrum antibiotics. Therefore, we investigated whether an antibiotic stewardship intervention would reduce the use of broad-spectrum antibiotics in patients with moderately severe community-acquired pneumonia without compromising their safety. Methods In this cross-sectional, stepped-wedge, cluster-randomised, non-inferiority trial (CAP-PACT) done in 12 hospitals in the Netherlands, we enrolled immunocompetent adults (≥18 years) who were admitted to a non-ICU ward and had a working diagnosis of moderately severe community-acquired pneumonia. All participating hospitals started in a control period and every 3 months a block of two hospitals transitioned from the control to the intervention period, with all hospitals eventually ending in the intervention period. The unit of randomisation was the hospital (cluster), and electronic randomisation (by an independent data manager) decided the sequence (the time of intervention) by which hospitals would cross over from the control period to the intervention period. Blinding was not possible. The antimicrobial stewardship intervention was a bundle targeting health-care providers and comprised education, engaging opinion leaders, and prospective audit and feedback of antibiotic use. The co-primary outcomes were broad-spectrum days of therapy per patient, tested by superiority, and 90-day all-cause mortality, tested by non-inferiority with a non-inferiority margin of 3%, and were analysed in the intention-to-treat population, comprising all patients who were enrolled in the control and intervention periods. This trial was prospectively registered at ClinicalTrials.gov , NCT02604628 . Findings Between Nov 1, 2015, and Nov 1, 2017, 5683 patients were assessed for eligibility, of whom 4084 (2235 in the control period and 1849 in the intervention period) were included in the intention-to-treat analysis. The adjusted mean broad-spectrum days of therapy per patient were reduced from 6·5 days in the control period to 4·8 days in the intervention period, yielding an absolute reduction of –1·7 days (95% CI –2·4 to –1·1) and a relative reduction of 26·6% (95% CI 18·0–35·3). Crude 90-day mortality was 10·9% (242 of 2228 died) in the control period and 10·8% (199 of 1841) in the intervention period, yielding an adjusted absolute risk difference of 0·4% (90% CI –2·7 to 2·4), indicating non-inferiority. Interpretation In patients hospitalised with moderately severe community-acquired pneumonia, a multifaceted antibiotic stewardship intervention might safely reduce broad-spectrum antibiotic use. Funding None.

Background Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19. Methods In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. Results The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65–2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71–1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. Conclusions BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection. Clinical trials registration EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.

Objectives Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [18F]FDG-PET/CT radiomics, SUVmax and biochemical profile for the identification of the genetic clusters of PPGLs. Methods In this single-centre cohort, 40 PPGLs (13 cluster 1, 18 cluster 2, 9 sporadic) were delineated using a 41% adaptive threshold of SUVpeak ([18F]FDG-PET) and manually (low-dose CT; ldCT). Using PyRadiomics, 211 radiomic features were extracted. Stratified 5-fold cross-validation for the identification of the genetic cluster was performed using multinomial logistic regression with dimensionality reduction incorporated per fold. Classification performances of biochemistry, SUVmax and PET(/CT) radiomic models were compared and presented as mean (multiclass) test AUCs over the five folds. Results were validated using a sham experiment, randomly shuffling the outcome labels. Results The model with biochemistry only could identify the genetic cluster (multiclass AUC 0.60). The three-factor PET model had the best classification performance (multiclass AUC 0.88). A simplified model with only SUVmax performed almost similarly. Addition of ldCT features and biochemistry decreased the classification performances. All sham AUCs were approximately 0.50. Conclusion PET radiomics achieves a better identification of PPGLs compared to biochemistry, SUVmax, ldCT radiomics and combined approaches, especially for the differentiation of sporadic PPGLs. Nevertheless, a model with SUVmax alone might be preferred clinically, weighing model performances against laborious radiomic analysis. The limited added value of radiomics to the overall classification performance for PPGL should be validated in a larger external cohort. Key Points • Radiomics derived from [18F]FDG-PET/CT has the potential to improve the identification of the genetic clusters of pheochromocytomas and paragangliomas. • A simplified model with SUVmaxonly might be preferred clinically, weighing model performances against the laborious radiomic analysis. • Cluster 1 and 2 PPGLs generally present distinctive characteristics that can be captured using [18F]FDG-PET imaging. Sporadic PPGLs appear more heterogeneous, frequently resembling cluster 2 PPGLs and occasionally resembling cluster 1 PPGLs.

October 31, 2022

June 16, 2020

June 17, 2020

September 19, 2022

Furans derived from carbohydrate feedstocks are a versatile class of bio-renewable building blocks and have been used extensively to access 7-oxanorbornenes via Diels-Alder reactions. Due to their substitution patterns these furans typically have two different π-faces and therefore furnish racemates in [4 + 2]-cycloadditions. We report the use of an enantiopure glucosamine derived furan that under kinetic conditions predominantly affords the exo-product with a high π-face selectivity of 6.5 : 1. The structure of the product has been resolved unequivocally by X-ray crystallography, and a multi-gram synthesis (2.8 g, 58% yield) confirms the facile accessibility of this multifunctional enantiopure building block.

Supplemental material, sj-pdf-1-tct-10.1177_15330338221125003 for The Influence of Irreversible Electroporation Parameters on the Size of the Ablation Zone and Thermal Effects: A Systematic Review by Annemiek M Hogenes, MSc, Christiaan G Overduin, PhD, Cornelis H Slump, PhD, Cornelis J H M van Laarhoven, MD, PhD, Jurgen J Fütterer, MD, PhD, Richard P G ten Broek, MD, PhD, and Martijn W J Stommel, MD, PhD in Technology in Cancer Research & Treatment

Contains fulltext : 292311.pdf (Publisher’s version ) (Open Access) Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection.

Supplemental material, sj-pdf-1-tct-10.1177_15330338221125003 for The Influence of Irreversible Electroporation Parameters on the Size of the Ablation Zone and Thermal Effects: A Systematic Review by Annemiek M Hogenes, MSc, Christiaan G Overduin, PhD, Cornelis H Slump, PhD, Cornelis J H M van Laarhoven, MD, PhD, Jurgen J Fütterer, MD, PhD, Richard P G ten Broek, MD, PhD, and Martijn W J Stommel, MD, PhD in Technology in Cancer Research & Treatment

Item does not contain fulltext Measurement and production of traditional prosthetic sockets are time-consuming, labor-intensive, and highly dependent on the personnel involved. An alternative way to make prostheses is using computer-aided design (CAD) and computer-aided manufacturing (CAM). Fused Filament Fabrication (FFF) may be an alternative to make low-cost prosthetic sockets. This study investigates the tensile properties of potential printing materials suitable for FFF according to ISO527 (Standard Test Method for Tensile Properties of Plastics). To ensure that FFF-printed sockets are safe for patient usage, the structural integrity of the 3D-printed prosthesis will be investigated according to ISO10328 (International Standard Structural Testing of Lower Limb Prostheses). Tough PLA was the most suitable print material according to ISO 527 testing. The Tough PLA printed socket completed 2.27 million cycles and a static test target value of 4025 N. Future research remains necessary to continue testing new potential materials, improve print settings, and improve the socket design for the production of FFF-printed transtibial prosthetic sockets. FFF using Tough PLA can be used to create transtibial prostheses that almost comply with the International Standard for Structural Testing of Lower Limb Prostheses.

Background: Osteoporosis is a metabolic bone disease, which impairs and/or delays the regenerative response of calcified tissues. Aim: The aim of this study was to assess the histopathologic response to direct pulp capping in osteoporotic rats that received a preoperative treatment with Zoledronic acid, a bisphosphonate which is currently prescribed for treating osteoporosis. Methodology: Two groups, each with 7 osteoporotic female Wistar rats (n=7) received either an intravenous dose of 100 mg/kg of Zoledronic Acid (Group 1) or the same volume of sterile saline (Group 2). One week later, the pulps of the right and left mandibular first molars of each animal were exposed and capped with Biodentine. After 20 days the animals in Group 1 received a second similar dose of Zoledronic acid and Group 2 a similar second dose of sterile saline. After 38 days the animals were euthanized and a total of 28 teeth (14 per group) were prepared for histologic analysis evaluating the following parameters: inflammation, reparative hard tissue formation, odontoblast cell layer organization, fibrous tissue, and necrosis. Results: In Group 1 the reparative hard tissue formation was scarce with preservation of the pulp tissue structure and the odontoblast cell layer. In Group 2 the pulp was preserved as a fibrous reticular-like structure. Reparative hard tissue formation was totally absent and the odontoblast cell layer was atrophic or absent. In both groups, no inflammation or necrosis was observed. Conclusions: The intravenous administration of Bisphosphonate (Zoledronic Acid) did not promote pulp healing in osteoporotic rats.

BackgroundBacillus Calmette-Guerin (BCG) vaccination has been hypothesised to reduce SARS-CoV-2 infection, severity, and/or duration via trained immunity induction.MethodsHealthcare workers (HCWs) in 9 Dutch hospitals were randomised to BCG or placebo vaccination (1:1) in March/April 2020 and followed for one year. They reported daily symptoms, SARS-CoV-2 test results, and healthcare-seeking behaviour via a smartphone application, and donated blood for SARS-CoV-2 serology at two time points.Results1,511 HCWs were randomised and 1,309 analysed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio=0.95; 95% confidence interval 0.76-1.21; p=0.732). Only three participants required hospitalisation for COVID-19. The proportions of participants with asymptomatic, mild, or mild-to-moderate infections, and the mean infection durations, did not differ between randomisation groups. Unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes either. The percentage of participants with seroconversion (7.8% versus 2.8%; p=0.006) and mean anti-S1 antibody concentration (13.1 versus 4.3 IU/ml; p=0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months post-vaccination.ConclusionsBCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (on a scale from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection.

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved.

BACKGROUND Assessing frailty in patients with an acute trauma can be challenging. To provide trustworthy results, tools should be feasible and reliable. This systematic review evaluated existing evidence on the feasibility and reliability of frailty assessment tools applied in acute in-hospital trauma patients. METHODS A systematic search was conducted in relevant databases until February 2020. Studies evaluating the feasibility and/or reliability of a multidimensional frailty assessment tool used to identify frail trauma patients were identified. The feasibility and reliability results and the risk of bias of included studies were assessed. This study was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and registered in Prospective Register of Systematic Reviews (ID: CRD42020175003). RESULTS Nineteen studies evaluating 12 frailty assessment tools were included. The risk of bias of the included studies was fair to good. The most frequently evaluated tool was the Clinical Frailty Scale (CFS) (n = 5). All studies evaluated feasibility in terms of the percentage of patients for whom frailty could be assessed; feasibility was high (median, 97%; range, 49-100%). Other feasibility aspects, including time needed for completion, tool availability and costs, availability of instructions, and necessity of training for users, were hardly reported. Reliability was only assessed in three studies, all evaluating the CFS. The interrater reliability varied between 42% and >90% agreement, with a Krippendorff α of 0.27 to 0.41. CONCLUSION Feasibility of most instruments was generally high. Other aspects were hardly reported. Reliability was only evaluated for the CFS with results varying from poor to good. The reliability of frailty assessment tools for acute trauma patients needs further critical evaluation to conclude whether assessment leads to trustworthy results that are useful in clinical practice. LEVEL OF EVIDENCE Systematic review, Level II.

The aim of this descriptive ex vivo study was to evaluate qualitatively the depth of pit and fissures (PF) of the enamel in human mandibular third molars. Fifty (n=50) extracted human mandibular third molars were cleaned and disinfected. All tooth surfaces were coated with nail varnish except for a 1-mm margin around the periphery of the occlusal surface. The teeth were immersed for 48 hours at 37 °C in 1% methylene blue dye solution prepared in artificial saliva. After cleaning, the crowns were separated from the root at the cementoenamel junction and subsequently sectioned longitudinally in buccolingual direction at the location of the central fossa. All sections were examined using a stereoscopic microscope and photographed. The images were downloaded on a computer. The length of penetration of the PF was recorded using the following scoring system: C1: PF extended to half of the enamel thickness; C2: PF extended beyond half of the enamel thickness without reaching the dentine-enamel junction; C3: PF extended to the dentine-enamel junction. For pits, C1, C2 and C3 were observed in 35, 9 and 6 teeth, respectively, while for fissures, C1, C2 and C3 were observed in 15, 18 and 17 teeth, respectively. The PF detected in the samples extended to the deepest portions of enamel, quite frequently reaching the enamel-dentine junction. Clinicians should recognize that even if pits and fissures are not clinically obvious, they penetrate deep into the enamel and frequently reach the dentine-enamel junction. Effective treatment is recommended to block access to PF, thus preventing ingress of bacteria.Objetivos: El objetivo del presente estudio descriptivo fue evaluar cualitativamente mediante un ensayo ex vivo la profundidad de las fosas y fisuras (FF) del esmalte en terceros molares inferiores humanos. Materiales y métodos: Cincuenta (n=50) terceros molares inferiores sanos extraídos se lavaron, se descontaminaron y se recubrieron con esmalte para uñas hasta 1 mm menos del área de las FF. Luego se sumergieron durante 48 horas a 37°C en una solución de azul de metileno al 1% (pH 7,4) preparada con saliva artificial. Posteriormente se lavaron y se separaron las coronas a nivel del límite amelocementario. En cada molar se realizó una sección longitudinal de 1 mm de espesor con orientación vestíbulo-lingual a nivel de la fosa central. Las secciones fueron analizadas con microscopio estereoscópico y fotografiadas. Las imágenes se transfirieron a una computadora. Se determinó cualitativamente la extensión de las FF en el espesor del esmalte y se las clasificó de acuerdo a 3 categorías. C1: extensión hasta la mitad del espesor del esmalte; C2: extensión que supera la mitad del espesor del esmalte sin afectar el límite amelodentinario; C3: extensión que llega al límite amelodentinario. Resultados: Para las fosas, 35, 9 y 6 especimenes correspondieron a las categorías C1, C2 y C3 respectivamente. Para las fisuras, 15, 18 y 17 especimenes correspondieron a las categorías C1, C2 y C3 respectivamente. Conclusiones: Las fosas y fisuras de la muestra analizada se extienden hasta la zona más profunda del espesor del esmalte. Con cierta frecuencia llegan hasta el límite amelodentinario.

Glycerol phosphate (GroP)-based teichoic acids (TAs) are antigenic cell-wall components found in both enterococcus and staphylococcus species. Their immunogenicity has been explored using both native and synthetic structures, but no details have yet been reported on the structural basis of their interaction with antibodies. This work represents the first case study in which a monoclonal antibody, generated against a synthetic TA, was developed and employed for molecular-level binding analysis using TA microarrays, ELISA, SPR- analyses, and STD-NMR spectroscopy. Our findings show that the number and the chirality of the GroP residues are crucial for interaction and that the sugar appendage contributes to the presentation of the backbone to the binding site of the antibody

Serum N-glycan profiling studies during the past decades have shown robust associations between N-glycan changes and various biological conditions, including infections, in humans. Similar studies are scarcer for other mammals, despite the tremendous potential of serum N-glycans as biomarkers for infectious diseases in animal models of human disease and in the veterinary context. To expand the knowledge of serum N-glycan profiles in important mammalian model systems, in this study, we combined MALDI-TOF-MS analysis and HILIC-UPLC profiling of released N-glycans together with glycosidase treatments to characterize the glycan structures present in rhesus macaque serum. We used this baseline to monitor changes in serum N-glycans during infection with Brugia malayi, a parasitic nematode of humans responsible for lymphatic filariasis, in a longitudinal cohort of infected rhesus macaques. Alterations of the HILIC-UPLC profile, notably of abundant structures, became evident as early as 5 weeks post-infection. Given its prominent role in the immune response, contribution of immunoglobulin G to serum N-glycans was investigated. Finally, comparison with similar N-glycan profiling performed during infection with the dog heartworm Dirofilaria immitis suggests that many changes observed in rhesus macaque serum N-glycans are specific for lymphatic filariasis.

Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP.The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial.This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice.ISRCTN, ISRCTN13042622. Registered on 5 September 2020.

Introduction: Cerenkov luminescence imaging (CLI) is a novel imaging technology that might have the ability to assess surgical margins intra-operatively during prostatectomy using Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11). This study evaluates the accuracy of CLI compared to histopathology and as exploratory objective investigates the characteristics of the identified chemiluminescence signal. Materials and Methods: After intravenous injection of a mean 68Ga-PSMA-11 activity of 69MBq intraoperatively, all excised specimens were imaged with CLI. Areas of increased signal were marked for histopathological comparison and scored for likelihood of being a positive surgical margin (PSM) using a 5-point Likert scale. In addition, the chemiluminescence signal was investigated in three radioactive and three non-radioactive specimens using CLI. Results: In 15 patients, the agreement between CLI and histopathology was 60%; this improved to 83% when including close surgical margins (≤1mm). In six hotspots, CLI correctly identified PSMs on histopathology, located at the apex and mid-prostate. In all 15 patients an increased signal at the prostate base was observed, without the presence of the primary tumor in this area in eight patients. This chemiluminescence signal was also observed in non-radioactive prostate specimens, with a half-life of 48±11min. The chemiluminescence hampered the visual interpretation of four PSMs at the base. Conclusion: CLI is able to correctly identify margin status, including close margins, in 83% of the cases. The presence of a diathermy-induced chemiluminescent signal hampered image interpretation, especially at the base of the prostate. In the current form, CLI is most applicable to detect PSMs and close margins in the apex and mid-prostate.

The point-of-care urine based strip test for the detection of circulating cathodic antigen (POC-CCA) in schistosome infections is a frequently used tool for diagnosis and mapping of Schistosoma mansoni in school-aged children. Because of its ease of use, the test is increasingly applied to adults and preschool-aged children (PSAC), but its performance has not been specifically evaluated in these target groups. Recent observations have raised concerns about possible reduced specificity, in particular in pregnant women (PW) and PSAC. We thus explored specificity of the POC-CCA urine strip test (Rapid Medical Diagnostics, Pretoria, South Africa) in a non-endemic, nonexposed population of 47 healthy nonpregnant adults (NPAs), 52 PW, and 58 PSAC. A total of 157 urines were tested with POC-CCA, of which five (10.6%) NPAs, 17 (32.7%) PW, and 27 (46.5%) PSAC were positive. The highest scores were found in the youngest babies, with an infant of 9 months being the oldest positive case. On measuring pH, it appeared that all POC-CCA strongly positive urines were acidic (pH range 5–5.5), whereas addition of pH-neutral buffer to a subsample reversed the false positivity. We conclude that the POC-CCA test has reduced specificity in PW and infants younger than 9 months, but that the false positivity might be eliminated by modifications in the buffers used in the test.

Ziele: Primäres Ziel der vorliegenden Studie war die Ermittlung der Zahl der Patienten, die während der vorangegangenen zehn Jahre in den Monaten Dezember und Januar mit Verletzungen durch Feuerwerkskörper ins Krankenhaus eingeliefert wurden; außerdem sollte der Zusammenhang zwischen der Art der Feuerwerkskörper, dem Verletzungsmuster, der Behandlung und den bleibenden Schäden beschrieben werden. Methoden: Bei der vorliegenden Untersuchung handelt sich um eine multizentrische, retrospektive Beobachtungs-Fallserie. Die Patienten stammten aus zwei Krankenhäusern im Südwesten der Niederlande: einem Level-1-Traumazentrum und einer Spezialklinik für Brandverletzungen. Alle Patienten mit Verletzungen durch Feuerwerkskörper, die in den Jahren 2007 (Dezember) bis 2017 (Januar) zwischen dem 1. Dezember und dem 31. Januar behandelt worden waren, kamen für die Teilnahme in Frage. Primäres Zielkriterium war die Anzahl der Patienten mit einer durch Feuerwerkskörper verursachten Verletzung. Sekundäre Zielkriterien waren die Patientenmerkmale und Verletzungscharakteristika, die Behandlungsdetails und die Schädigungsfolgen (whole person impairment, WPI). Der Grad der Schädigungsfolgen in Prozent drückt den Grad der dauerhaften Beeinträchtigung eines Patienten infolge von Verletzungen durch Feuerwerkskörper aus. Ergebnisse: Von 297 in Frage kommenden Patienten wurden 272 in die Studie eingeschlossen. Von 2007 bis 2017 wurden zwischen 21 und 40 Patienten behandelt, wobei kein eindeutiger Anstieg oder Rückgang der Patientenzahl und der Anzahl der Patienten pro Feuerwerkskörperart erkennbar war. Knallkörper verursachten vor allem Verletzungen der oberen Extremitäten (N = 65; 68%), wohingegen Raketen (N = 24; 41%) und Abschussrohre/-batterien (N = 7; 41%) überwiegend die Kopf/Hals-Region betrafen. Leuchtkörper hatten hauptsächlich Verbrennungen (N = 82; 68%) zur Folge und Knallkörper führten zu Weichteillazerationen (N = 24; 25%), Frakturen (N = 16; 17%) sowie Amputationen (N = 14; 15%). Patienten mit Verletzungen durch Knallkörper und selbstgebaute Feuerwerkskörper wurden am häufigsten ins Krankenhaus eingeliefert (N = 24; 36% bzw. N = 12; 80%) und bei ihnen war der Anteil operativer Eingriffe am höchsten (N = 22; 33% bzw. N = 7; 47%). Der in der vorliegenden Studie ermittelte WPI-Grad betrug zwischen 0 und 95% und der Median lag bei 0%. Bei 34 Patienten (14%) führten die Verletzungen zu einem WPI-Grad von ≥ 1%, meist als Folge einer Verwendung von Knallkörpern (N = 18; 53%). Schlussfolgerung: In dieser Studie war kein Anstieg oder Rückgang der Anzahl der in zwei Spezialkliniken behandelten Patienten zu beobachten. Knallkörper und selbstgebaute Feuerwerkskörper können als die gefährlichsten angesehen werden, da sie mit den meisten Krankenhauseinweisungen und operativen Eingriffen verbunden sind und am häufigsten Verletzungen mit bleibenden Schäden verursachen.

The Relay®Branch stent-graft (Terumo Aortic, Sunrise, FL, USA) offers a custom-made endovascular solution for complex aortic arch pathologies. In this technical note, a modified electrocardiography (ECG)-gated computed tomography (CT)-based algorithm was applied to quantify cardiac-pulsatility-induced changes of the aortic arch geometry and motion before and after double-branched endovascular repair (bTEVAR) of an aortic arch aneurysm. This software algorithm has the potential to provide novel and clinically relevant insights in the influence of bTEVAR on aortic anatomy, arterial compliance, and stent-graft dynamics.

There exists little to no data on the development of donor-site scars that remain after split skin graft harvesting. The objectives of this study were to (a) examine changes in characteristics of donor-site scar quality over time and (b) assess the agreement between patient-reported and observer-reported donor-site scar quality in a burn population. A prospective cohort study was conducted including patients who underwent split skin grafting for their burn injury. Patients and observers completed the Patient and Observer Scar Assessment Scale (POSAS) for the first harvested donor site at 3 and 12 months post-surgery. This study included 80 patients with a median age of 34 years. At 3 months post-surgery, the patients scored the POSAS items itch and color as most deviant from normal skin, both improved between 3 and 12 months (3.1 vs 1.5 and 5.0 vs 3.5, respectively [P '.001]). Other scar characteristics did not show significant change over time. The patients' overall opinion score improved from 3.9 to 3.2 (P '.001). Observers rated the items vascularization and pigmentation most severe, only vascularization improved significantly between both time points. Their overall opinion score decreased from 2.7 to 2.3 (P '.001). The inter-observer agreement between patients and observers was considered poor (ICC ' 0.4) at both time points. Results of current study indicate that observers underestimate the impact of donor-site scars. This has to be kept in mind while guiding therapy and expectations. LEVEL OF EVIDENCE: II, prospective cohort study.

The emergence of limb occlusion after endovascular aneurysm repair may be related to the conformational changes between the endograft structure and the patient's anatomy. This study analyzed detailed geometric changes of Anaconda endograft (Terumo Aortic, Inchinnan, Scotland, UK) limbs during the cardiac cycle–based computed tomography on serial imaging after graft implantation. Fifteen patients (mean age 72.8 ± 3.7 years; 14 men) underwent postoperative electrocardiogram-gated computed tomography scans according to a prospective study design between April 2014 and May 2017. Changes in curvature, length of the limbs, and distances between successive stent rings (inter-ring distance) of the endograft limbs during a 2-year follow-up period were quantified using meticulous image processing methods involving image registration, centerline extraction, and model-based stent-ring segmentation. From discharge to 24 months, mean curvature increased significantly by 9.6 m–1 (standard deviation [SD], 11.1 m–1; 95% confidence interval [CI], 3.4 to 15.8 m–1; P =.002) for the right limbs and by 6.1 m–1 (SD 9.4 m–1; 95% CI, 0.8 to 11.5 m–1; P =.21) for the left limbs. The length of the right limbs decreased significantly, by 9.5 mm (SD 7.6 mm; 95% CI, 3.5 to 15.6 mm; P =.002); the length of the left limbs decreased by 10.1 mm (SD 5.1 mm; 95% CI, 5.9 to 14.2 mm; P

Patients suffering from pectus excavatum often experience psychosocial distress due to perceived anomalies in their physical appearance. The ability to visually inform patients about their expected aesthetic outcome after surgical correction is still lacking. This study aims to develop an automatic, patient-specific model to predict aesthetic outcome after the Nuss procedure. Patients prospectively received preoperative and postoperative 3-dimensional optical surface scanning of their chest during the Nuss procedure. A prediction model was composed based on nonlinear least squares data-fitting, regression methods and a 2-dimensional Gaussian function with adjustable amplitude, variance, rotation, skewness, and kurtosis components. Morphological features of pectus excavatum were extracted from preoperative images using a previously developed surface analysis tool to generate a patient-specific model. Prediction accuracy was evaluated through cross-validation, utilizing the mean root squared deviation and maximum positive and negative deviations as performance measures. The prediction model was evaluated on 30 (90% male) prospectively imaged patients. The model achieved an average root mean squared deviation of 6.3 ± 2.0 mm, with average maximum positive and negative deviations of 12.7 ± 6.1 and -10.2 ± 5.7 mm, respectively, between the predicted and actual postoperative aesthetic result. Our developed 2-dimensional Gaussian model based on 3-dimensional optical surface images is a clinically promising tool to predict postsurgical aesthetic outcome in patients with pectus excavatum. Prediction of the aesthetic outcome after the Nuss procedure potentially improves information provision and expectation management among patients. Further research should assess whether increasing the sample size may reduce deviations and improve performance.