bluuebunny/crossref_metadata_2025 huggingface dataset:
54 Nickel Exposure During Abrasive Tasks – Influence of the Nickel Content of the Material
Authors: Koppisch Dorothea , Bünning Gunter , Pitzke Katrin , Gabriel Stefan
Published: May 2023

Nickel is widely used for the production of steel and alloys. It can provoke nickel allergy and several nickel compounds are classified as carcinogens. Data on the level of exposure of welders have been published repeatedly. However, data on nickel exposure during abrasive work are limited. The aim of this study is to estimate the nickel exposure during abrasive tasks taking into account the nickel content of the material. Data from the German exposure database MEGA are used for the study. The material used is classified according to its nickel content into three groups: less than 5% (mild steel); 5 to 30% (stainless steel); more than 30% (nickel-base alloy). Additionally task and year of measurement are defined as criteria for the statistical evaluations. Percentiles are calculated and, if sufficient data is available, regression methods are used. Between 1975 and 2016, about 6700 measurements from nickel in the inhalable dust fraction in MEGA are related to abrasive tasks. For grinding (wet and dry combined) the 50th percentile was 0.0024 mg Ni/m3 for mild steel, 0.052 mg/m3 for stainless steel and 0.16 mg/m3 for nickel-base alloys during 1990-2006. After 2006 measurements were mainly performed during dry grinding. These measurements resulted in similar exposures. Further results are presented for polishing, milling and drilling. The high differences in the level of exposure to nickel caused by different nickel content of the material show that this information should be collected when measuring nickel exposure at workplaces where abrasive tasks with steel and alloys are performed.
93 Microbial Contaminants and Pro-Inflammatory Properties of Organic Dust From Different Occupational Settings
Authors: Cyprowski Marcin , Zapór Lidia , Marciniak Lilianna , Gołofit-Szymczak Małgorzata , Ławniczek-Wałczyk Anna , Stobnicka-Kupiec Agata , Górny Rafał L
Published: May 2023

The study aimed to characterize the microbial contamination of dust samples from various occupational environments and to assess their impact on the release of pro-inflammatory cytokines from cell culture. The research was conducted in six occupational settings, including waste sorting and composting plants, a sewage treatment plant, a cement plant using alternative fuel, a power plant co-firing biomass as well as a poultry farm. In total, 76 organic dust samples were collected at 26 workplaces in the above-mentioned plants to assess the concentrations of: inhalable dust fraction, crystalline silica, aerobic and anaerobic bacteria, fungi as well as peptidoglycans, endotoxins and (1→3)-β-D-glucans. The alveolar epithelial cells (A549) were exposed to dust extracts and the levels of pro-inflammatory cytokines (IL-6 and IL-8) were determined. The highest inhalable dust concentrations were found in the power plant samples – 5.60 mg/m3 (SD=9.13). In poultry houses, the highest concentrations were noted for aerobic and anaerobic bacteria – 201129 cfu/m3 (SD=62795) and 72702 cfu/m3 (SD=13532), respectively. In turn, the waste sorting plant workplaces were the most contaminated with fungi – 36335 cfu/m3 (SD=27270), endotoxins – 23.9 ng/m3 (SD=21.5) and SiO2 – 0.024 mg/m3 (SD=0.026). The highest levels of peptidoglycans – 7930 ng/m3 (SD=6049) and (1→3)-β-D-glucans – 180.5 ng/m3 (SD=46.4) were found at workplaces in composting plant. The release of cytokines was significantly dependent (p<0.05) on dust concentrations for composting and cement plants; however, to a lesser extent, their production were also stimulated by aerobic bacteria, fungi, endotoxins and crystalline silica. The microbial characteristics of organic dusts may trigger the pro-inflammatory reactions in workers.
9 Understanding how CeO2 Nanoparticles Modulate Bleomycin-Induced Inflammatory and Fibrotic Events in Both in Vivo and in Vitro Models
Authors: Guo Chang , Leonard Martin , Buckley Alison , Robertson Sarah , Gant Tim , Valsami-Jones Eugenia (Éva) , Smith Rachel
Published: May 2023

Cerium oxide nanoparticles (CeO2NPs) from some diesel fuel additives and other applications have been detected in ambient air. Concerns have been raised over their potential human health impact in situations of inadvertent exposure. Oxidative mechanisms have been suggested as a common feature for pulmonary injury in response to airborne particulate matter, including engineered nanomaterials. To understand in depth how CeO2NPs may influence oxidative stress induced pulmonary inflammation and fibrotic events, we used both in vivo and in vitro bleomycin-induced lung injury models. Male Sprague-Dawley rats were intratracheally instilled with bleomycin or saline (control) followed by nose-only inhalation exposure to nano-sized CeO2NP aerosols (mass concentration 1.8 mg/m3) or water (controls) for 3 hours per day for 4 days per week for one or two weeks. At 3 days post exposure, animals were sacrificed and bronchoalveolar lavage (BAL) fluid, lung histopathology and global mRNA expression analysed. Bleomycin exposure resulted in an increase in total BAL cells, fibrotic staining and significant induction of inflammatory and oxidative stress on mRNA sequencing analysis. Modifications of these responses by one-week exposure to CeO2NPs included attenuation of fibrotic staining and gene expression markers of lung function, inflammation and epithelial-mesenchymal transition (EMT). CeO2NP alone resulted in increased inflammatory responses but did not appear to cause fibrotic changes. Interpretation of these responses at a cellular level was further explored using 3D human small airway epithelium cultures (SmallAirTM) in an aerosol exposure air-liquid-interface system. This also indicated that some bleomycin-induced cellular responses could be attenuated by exposure to CeO2NP aerosols.
62 Evaluating the Potential Exposure to Metal Fine and Nano Particles Generated During Wire and Powder Laser Metal Deposition
Authors: Pernetti Roberta , Previtali Barbara , Maffia Simone , Bergamaschi Enrico , Oddone Enrico
Published: May 2023

This study aims to evaluate the release of fine and nano particles during Additive Manufacturing with wire and powder Laser Metal Deposition where the layers of metal feedstock are deposited and contemporaneously melted by a high-energy beam during the building phase. We analysed an experimental set-up in a research laboratory equipped with two different nozzles: one operates by jetting powder while the second by depositing a metal wire. The campaign included environmental and personal monitoring during whole processes adopting AISI-316L as feedstock. Fine particles are assessed by the optical counter Lighthouse3016-IAQ, allowing to detect six size classes (0.3-10 µm). DiSCmini was used for measuring number and average diameter of nanoparticles (10-300 nm). A significant release of nanoparticles occurred with both nozzles during the building phase and, although the peaks were higher when using the powder nozzle (2.9 x 106 n/cm3), the average values were around five times higher with the wire nozzle (6.5 x 105 n/cm3, 75 nm). Adopting the wire nozzle reduced the particle emissions during initialization and cleaning phase, avoiding handling powders. Considering the state of the art and industrial practice, the relevant novelty of the work lays in the detection of nanoparticles even for wire laser metal deposition due to the melting and partial vaporisation phenomena induced by the high-power density of the laser beam. The results highlight the importance of adopting proper working procedures and personal protective equipment for the operators entering the box when interrupting the building phase with both powder and wire nozzles.
118 Murine Expression of Humanized Toll-Like Receptor 4 Augments Local and Systemic Immune Responses Following Oropharyngeal Aspiration of Nickel Oxide Nanoparticles
Authors: Roach Katie , Stefaniak Aleks , Roberts Jenny
Published: May 2023

It has been demonstrated that murine expression of humanized Toll-like receptor-4 (hTLR-4) confers enhanced immunological responsivity to nickel in the skin; however, it remains unclear if hTLR-4 expression also augments nickel-induced immune responses in the lung. hTLR-4 positive/negative mice of both sexes were exposed to vehicle control (dispersion media) or nickel oxide nanoparticles (NiONP; 48 nm; 2.5, 5, or 20 µg) by oropharyngeal aspiration. Mice were euthanized 1, 7, 14, or 28 days post-exposure. Bronchoalveolar lavage (BAL) was performed, blood was collected, and the lung-associated lymph nodes (LALN) and spleen were harvested for phenotypic analysis. By 7d, total BAL cells, lung LDH, and circulating leukocyte number were all significantly elevated in both female/male hTLR-4 positive mice compared to same-sex hTLR-4 negative mice—effects which normalized by 14d. Dose-responsive increases in LALN size were observed in all NiONP-exposed animals by 14d, but no significant differences were observed between hTLR-4 positive/negative animals. The cellular composition of the LALN and spleen, however, was significantly altered at this timepoint between hTLR-4 positive/negative mice of both sexes. In general, hTLR-4 positive mice exhibited selective increases in proportionality and activation status of CD4+ T-cells and B-cells within both tissues. This alteration remained significant at 28d in female mice only. Collectively, these findings suggest that hTLR-4 expression confers significant alterations in early immune responses to NiONP in the lung and associated lymphoid tissues—effects which may render the hTLR-4 mouse model a more translationally-relevant approach for studying respiratory nickel allergy in vivo.
130 Exposures to Airborne Human-Respirable Microplastic Particles
Authors: Elder Alison , Chalupa David , Romanick Samantha , Madejski Gregory , McGrath James
Published: May 2023

Plastics and their breakdown products, specifically microplastics, are ubiquitously present in the environment from a variety of sources. Analysis of air samples has also revealed the presence of fragmented, spherical, and fibrous plastic particles in a wide range of sizes from the submicrometer scale up to tens of micrometers in length and diameter. However, few studies have addressed the health consequences associated with exposures to airborne microplastics, specifically whether they can enter the respiratory tract, where they will deposit, and how polymer chemistry and morphology are linked to adverse health outcomes. Whether microplastics have unique toxicological properties in comparison to other particle types is also unknown. Our work has sought to address critical questions about the inhalability and respirability of microplastics in indoor and outdoor air via particle size-restricted sampling coupled with morphological assessment and estimation of plastic burdens via Nile red staining. We found Nile red-positive (putative plastic) particles in air samples from indoor environments (office, campus/household laundry rooms, 3-D printing/engineering laboratory), most of which appeared to have a fragment-like morphology. These particles represented ~1% of the total collected sample in terms of number. Importantly, these particles were also found when sampling was restricted to the human-respirable fraction (<4 micrometers in aerodynamic diameter), suggesting that they can reach the gas exchange region. Ongoing work is focused on identifying the polymeric species in these air samples, their distribution across particle size classes, and whether indoor and outdoor microplastic particles are similar in terms of morphology, size, and chemistry.
151 TRPA1/V3-Dependent Regulation of Airway Epithelial Cell Damage and Repair Triggered by wood/Biomass Smoke Particulate
Authors: Serna Samantha , Golkowski Martin , Reilly Christopher
Published: May 2023

Wood/biomass smoke particulate material (WBSPM) is a pervasive environmental pollutant. Acute high-dose inhalation exposure can cause airway epithelial cell (AEC) damage and respiratory dysfunction. We hypothesized that AEC damage is limited by compensatory signaling to allow epithelial repair. RNA sequencing, proteomics, targeted interventions, and cultured human AECs treated with WBSPM and Transient Receptor Potential Ankyrin-1 (TRPA1) agonists revealed TRPA1-driven endoplasmic reticulum stress (ERS) and oxidative stress (OS) as contributory pathways to cytotoxicity. Alternatively, TRP vanilloid-3 (TRPV3) counteracted these events despite also being activated by WBSPM. Using the TRPA1 agonist AITC (and others) as a surrogate for WBSPM, morphological distortion indicative of AEC damage was observed 2-4h post-treatment; at >6h cells recovered. Strikingly, at 2h, the abundance of only 6 proteins changed including loss of fibronectin and tubulin and increased heme oxygenase 1. At 6h, 36 proteins changed, including ER chaperones and transcriptional/cell cycle regulatory proteins, OS-response, and structural/matrix proteins. Analysis of the phosphoproteome revealed changes in 2672 and 1886 unique phosphosites at 2 and 6h, attributable to PKC, p38 MAPK, EGFR, Akt and other kinase activities based on “phosphosite-GSEA” analysis. A kinase inhibitor screen linked PKC, p38 MAPK, GSK3b and ERK1/2 with cytotoxicity, while EGFR, MEK1/2, JNK1/2/3 and Akt were protective. Considering that TRPV3 expression is regulated by EGFR following WBSPM injury and TRPV3 enhanced adhesion and slowed proliferation via attenuated EGFR signaling, we propose a mechanism whereby the balance of TRPA1, TRPV3, and calcium/growth factor receptor-dependent kinase signaling coordinates WBSPM injury, compensation and repair.
4 An Introduction to the Sunshine Project Investigating the Risk Assessment of Multicomponent Nanomaterials.
Authors: Hunt Neil
Published: May 2023

Multicomponent nanomaterials (MCNM), sometimes called nanohybrids, are advanced materials receiving increased interest in their novel or enhanced properties.   Research into MCNM is in its infancy meaning that little is known about their hazard, risk or whether there is regulatory preparedness for their increased use.  SUNSHINE is an industry-oriented project, where leading research and technology organisations will cooperate with SMEs and large industries to develop and implement simple, robust, and cost-effective Safe and Sustainable by Design (SSbD) strategies for materials and products incorporating advanced multi-component nanomaterials. This presentation will introduce the key elements in the project including investigations into whether existing characterisation and toxicology testing protocols are applicable and whether existing regulatory frameworks are fit for purpose for these complex structures.  It will also introduce how MCNM are being used as a case study for the use of the Safe and Sustainable by Design framework. 

SUNSHINE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 952924.
76 Combined Exposure to road wear Particles and Diesel Exhaust Particles Induces Enhanced pro-Inflammatory Responses in Cells of the Human Airways
Authors: ter Grytting Vegard Sæ , Kirkerød Elisabeth , Skuland Tonje , Refsnes Magne , Øvrevik Johan , Gustafsson Mats , Låg Marit
Published: May 2023

Ambient particulate matter (PM) is one of the leading environmental mortality risk factors worldwide. PM is not a single entity but consists of a complex and variable mixture of particles from multiple sources. Nevertheless, there is a paucity of experimental studies assessing the potential combinatory effects of different types of particles, and most focus on the effects of individual PM components or mixed PM samples. In the present study, the pro-inflammatory effects of combined exposure to road wear particles and diesel exhaust particles (DEP), two important constituents of traffic-derived PM, were assessed in vitro. Human bronchial epithelial cells (HBEC3-KT) and differentiated THP-1 macrophage-like cells were exposed to road wear particles and two different samples of DEP under submerged conditions, both alone and in combination. Particle-induced release of pro-inflammatory cytokines (CXCL8 and IL-1β) was measured by enzyme-linked immunosorbent assay. The results show that combined exposure to road wear particles and DEP induced enhanced release of pro-inflammatory cytokines compared with the effects of the individual particle samples. The combinatory effects appeared to depend on properties of the DEP samples and also differed between the HBEC3-KT cells and THP-1 macrophage-like cells. This study shows that the effects of combined exposure to different types of particles may surpass the effects anticipated by the effects of the individual particulates. These combinatory effects between types of particles could have implications when assessing measures to reduce PM-induced health effects.
77 Aerosolized Particulate Matter from Fragmentation of Carbon Nanotube-Enhanced Concrete
Authors: Abrahamsson Camilla , Rissler Jenny , Hedmer Maria , Kåredal Monica , Isaxon Christina
Published: May 2023

Construction and demolition workers are exposed to high levels of particulate matter (PM) from building materials throughout their working life. Although nano-enabled building materials (NEBMs) may improve the performance and functionality of buildings, concerns are being raised regarding health risks from occupational exposure to PM from NEBMs. In this work, an experimental set-up for integrated resuspension and characterization of PM from NEBMs was developed and tested using three types of concrete (low density, normal, high strength), each enhanced with Carbon Nanotubes (CNTs) at different concentrations (0, low, high). The performance of portable devices used in occupational exposure assessments (DustTrak and NanoTracer) was compared with stationary instruments and gravimetric filter techniques. 40-70% of the mass and 90-98% of the number of particles were within the respirable fraction, with primary modes at 150 nm and 2-3 µm. Addition of CNTs significantly decreased mean particle number concentrations (PNCs) across the entire characterized size range (7 nm - 20 µm) for low density concrete, whereas the opposite was the case for normal strength and high strength concrete. It was hypothesised that the concrete matrix primarily governs the PM formation, which is in turn modulated by CNT-matrix interactions either suppressing or supporting fragmentation during crushing. SEM imaging could display partially submerged CNTs protruding from concrete fragments. Fundamental interactions at the interface of the nanomaterial and the surrounding matrix needs to be investigated to determine how the PM generated from NEBMs differ from their non-nano counterparts and how to prevent future exposure during demolition.
104 Influence of the Physicochemical Properties of Multi-Walled Carbon Nanotubes on Their Toxicity in Lung Cells
Authors: Seidel Carole , Sébillaud Sylvie , Darne Christian , Barthel Hélène , Gaté Laurent
Published: May 2023

Multi-walled carbon nanotubes (MWCNTs) are promising nanomaterials because of their various physicochemical properties. However, their production and handling can lead to their aerosolization. Then, they can be inhaled, reach the deep lung and induce health effects. The respiratory system is composed of different cell types, including epithelial cells and alveolar macrophages, which are on the front line following inhalation of MWCNTs. The aim of this study was to evaluate the influence of their physicochemical properties on their toxic effects. To address this objective, we use two in vitro models, NR8383 rat alveolar macrophages and BEAS-2B human bronchial epithelial cells. BEAS-2B cells are treated with low concentrations of nanomaterials for 6 weeks in order to evaluate a potential epithelial-mesenchymal transition (EMT). NR8383 macrophages are treated for up to 24 hours in order to study their polarization and cell signalling. The first results show that the treatment of BEAS-2B cells induced a modification of their phenotype in a differential time-scale and concentration depending on the MWCNT. This modification is accompanied by a change in the expression of genes specific to EMT. In addition, the treatment of NR8383 induced a modification of cell signalling, which can be observed in particular through the expression of transmembrane receptors and that of pro-inflammatory cytokines. The differential effects observed following treatment of the cells with the different types of MWCNTs can be considered regarding their physical properties, such as their length, diameter and specific surface area, as well as their chemical properties, in other terms their functionalization.
109 Inter- and Intra-Laboratory Comparison of 6 Dustiness Testing Methods: Towards the Development of an OECD Testing Guideline
Authors: Carrasco Carla Ribalta , Fonseca Ana Sofia , Pohl Anna , Vignes Alexis , Bjerregaard Søren S , Shandilya Neeraj , Evans Douglas , Kuhlbusch Thomas A J , Bouillard Jacques , Jensen Keld A
Published: May 2023

Dustiness is a key parameter describing the ability of powder materials to generate dust during agitation. The main goal of this work was to generate and assess the scientific basis for the validation and applicability of 6 dustiness methods to nanomaterials, and development of a subsequent OECD testing guideline. Six dustiness methods (rotating drum, small rotating drum, continuous drop, vortex shaker, fluidizer and venturi) were subjected to an intra- and inter-laboratory comparison (ILC) in which 15 international laboratories participated. ILC tests were conducted for 6 materials (3 TiO2 and 3 SiO2) of different chemical natures and dustiness levels. Each participating laboratory conducted at least 3 replicates per material. Harmonization of procedures, methods and data treatment took place prior to testing. Results from the ILC were assessed considering the different reported metrics such as respirable mass and particle number dustiness index. Overall, the intralaboratory variability for the different methods and metrics was under 30%. Variation between laboratories was generally higher for respirable mass than particle number dustiness index. These variations were mostly attributed to differences in setups such as tubing length or instrumentation. All methods except the venturi, which was characteristic for presenting low differences between materials and opposed classification to the rest of the methods, showed relatively similar material ranking. For all methods and laboratories the calculated z-score (measure of the deviation of each laboratory from the true value) was <2 as based on ISO 13528, which indicates gratifying results.

Funding: EU H2020 Research and Innovation Programme under Grant Agreement 814401.
Incidence and prevalence of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using routinely captured electronic health records in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020
Authors: Choon Siew Eng , Wright Alison K , Griffiths Christopher E M , Wong Kit Wan , Tey Kwee Eng  , Lim Yee Ting , Chua Keow Yin , Ashcroft Darren M
Published: May 2023

Background

There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia.

Objectives

To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.

Methods

We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.

Results

The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8–31.6]; 35.3 (28.4–42.2) per million person-years for women and 18.3 (13.1–23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9–54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4–29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8–36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6–23.0) vs. 8.0 (95% CI 5.6–10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20–29 years and age 50–59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.

Conclusions

Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.
O090 TRANSCRIPTOMICS OF BREAST CANCER TUMOUR AND NORMAL ADJACENT TUMOUR TISSUE REVEAL DIFFERENTIAL IMMUNE-ADIPOSE-CANCER GENE EXPRESSION
Authors: Foley C , Cullinane C , Redmond H P
Published: May 2023

Introduction

Surgical-related immunity dysfunction in normal adjacent tumour (NAT) tissue of breast cancer (BC) patients is associated with BC recurrence. Characterising inflammation and immunosuppression in NAT tissue at the time of surgical excision of the tumour, using transcriptomics, may reveal a tissue phenotype more vulnerable to surgical-related immunity dysfunction.

Methods

RNA-Seq read counts from matched BC patient tumour and NAT tissues from the cancer genome atlas (TCGA) (n=54) and from University College Cork (UCC) & Cork University Hospital (CUH) biobank (n=10) were used. Differential gene expression was analysed using EdgeR and pathway analysis by Gene Set Enrichment Analysis using Hallmark gene sets. Immune cell subsets were deconvoluted using CIBERSORTx using the LM22 signature matrix. Genes were significantly different with a False Discovery Rate (FDR)<0.1 and pathways enriched with an FDR<0.25.

Results

Adipogenesis and IL6 JAK STAT3 signalling pathways were enriched in NAT and not in tumour tissue (FDR<0.25). Adipogenesis genes ADIPOQ, FABP4, CD36, LPL and PPARG and IL6 were significantly upregulated in NAT relative to tumour (FDR<0.1). Patients stratified on NAT expression of these genes, with higher expression had worse overall survival (OS)(p<0.05). There was no difference in patient OS, stratified on tumour expression of ADIPOQ and IL6. M2 macrophages were significantly increased in NAT relative to tumour(p<0.05). Patients with more M2 macrophages in tumours had significantly worse OS(p<0.05). There was no difference in OS for NAT tissue with more M2 macrophages.

Conclusion

Surgical-related immunity dysfunction in NAT breast tissue, may worsen postoperative immune-adipose-residual breast cancer cell interactions, contributing to poorer patient outcome.
O102 Rapid evaporative ionisation mass spectrometry (REIMS) coupled with the hydrosurgical debridement system and the carbon dioxide surgical laser: a proof of concept study in porcine tissues
Authors: Pruekprasert K , Simon D , Davies A , Takats Z , Onida S
Published: May 2023

Introduction

Rapid evaporative ionisation mass spectrometry (REIMS) is a tissue profiling technology that allows for rapid information. The successful integration of this technology with surgical devices can be beneficial for diagnostic, prognostic, and individualised treatment purposes.

Objectives

To access the feasibility of coupling REIMS with the hydrosurgical debridement device and the carbon dioxide surgical laser.

Methods

The 3D printing attachments and circuit connections were designed for device couplings. The aerosols generated from the hydrosurgical debridement device in terms of mist (applying to porcine liver vs kidney tissue samples), and the carbon dioxide laser in terms of smoke (applying to porcine liver vs kidney cortex vs kidney medulla) were collected for REIMS analysis. The abstract models for tissue classification were built from the obtained mass spectrometry data using the linear discriminant analysis (LDA) dimensional reduction technique. The abstract models were cross-validated and the real-time classifications of different tissue types were tested in both coupling platforms.

Results

The real-time spectral data signals were reliably achieved from both coupling platforms. For REIMS-hydrosurgical debridement coupling, the abstract model was successfully built from 804 spectra obtained from multiple porcine liver and kidney samples. The cross-validation resulted in 98.01% correct classification rate between the two types of tissue. For REIMS-carbon dioxide laser platform, the abstract model built from 1,454 spectra of porcine tissue samples (liver vs kidney cortex vs kidney medulla) demonstrated 94.36% correct classification rate of the three tissue types.

Conclusion

REIMS can be coupled with the hydrosurgical debridement device and the carbon dioxide surgical laser with accurate real-time classification of porcine tissues. These platforms have the potential for future translational applications in the clinical arena.
O109 Pelvic fracture incidence in EU15+ countries: trends over a 30-year period
Authors: Hagroo A , Ali R , Goodall R , Sugand K , Borsky K , Salciccioli J , Marshall D , Shalhoub J
Published: May 2023

Introduction

Pelvic fractures (PF) are relatively uncommon but account for approximately 3% of all skeletal injuries. We aimed to assess the burden of PFs across high health expenditure countries by describing the trends in PF incidence rates over the last three decades.

Methods

Using the Global Burden of Disease (GBD) Study database, we extracted sex specific PF age-standardised incidence rates (ASIRs) from 1990-2019 for each of the 19 European Union (EU) 15+ countries. We performed Joinpoint regression analysis to characterise the trends.

Results

Over the 30-year period of study, 89% of countries experienced a decline in ASIRs for males, with a median percentage change of -11.8%, in comparison to females where 53% of countries experienced an increase in ASIR (median percentage increase of +3.1%). For females, the largest increases in PF incidence were observed in the Netherlands and Belgium; these were also the only two counties with increased overall PF incidence in males over the study period observed. The countries with the greatest decrease in ASIRs were Italy and Denmark for females and Portugal and Spain for males. Joinpoint regression identified that over the time periods covered by the most recent trends, PF incidence rates had increased in 58% of countries for females and 52% of countries for males.

Conclusion

We found overall decreased incidences of PFs amongst males over the last 3 decades, compared with increased incidence in females. However, joinpoint regression analysis demonstrated a trend towards rising incidence of PFs amongst both males and females in recent years.
O114 Non-traumatic osteonecrosis of femoral head and its association with cardio-vascular disease: a case control study
Authors: Srivastava S , Menon J , Austine J , Ramesh A , Ahuja S
Published: May 2023

Introduction

Many parallels have been drawn in the past between the ischaemic process in the femoral head and in other organs like the heart (myocardial ischemia) and brain (stroke) suggesting similarities in their etio-pathogenesis. We aimed to study the relationship between coronary heart disease after non-traumatic osteonecrosis of femoral head (ONFH) by assessing the cardio-vascular profile utilizing non-invasive methods.

Methods

A case-control study was conducted at a tertiary care hospital to determine the association between non-traumatic ONFH and cardio-vascular pathology using non-invasive methods that assessed intravascular (lipid profile), microvascular (retinal fundoscopy) and macrovascular (ophthalmic and carotid doppler) parameters.

Results

48 patients were analysed, which comprised 24 cases and 24 controls, with each group consisting of 16 males and 8 females. Mean age of cases and controls were 37.08 ± 11.81 and 37.25 ± 11.67. Steroid intake (45.83%) was the most common predisposing factor, followed by chronic alcohol intake(25%). The ophthalmic and carotid artery doppler and lipid profile measurements did not find any statistically significant difference between the cases and controls. Fundus examination revealed C/D ratio of <0.3, foveal reflex and normal optic disc in all cases.

Conclusion

Though it is believed that non-traumatic osteonecrosis of the femoral head precedes the development of coronary artery disease, our study did not identify any significant relationship between the two when assessed by colour doppler of the ophthalmic and carotid arteries. The lipid profile characteristics of cases and controls showed no statistically significant variation.
O125 The impact of R0 versus R1 resection on survival after surgery for pancreatic cancer and distal cholangiocarcinoma
Authors: Adiamah A , Mohammad F , Hanks M , Wong T , Kandiah K , Zaitoun A M , Lobo D N
Published: May 2023

Introduction

Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma are characterised by poor overall survival, even after curative resection. We sought to determine if R0 versus R1 status affected survival.

Methods

This retrospective study included patients who underwent pancreatic resection for PDAC or distal cholangiocarcinoma between Jan 2001 and Dec 2021 at a tertiary HPB unit in the UK. Demographic characteristics and operative outcomes were compared using chi-squared testing and Mann Whitney-U test. The overall survival was determined using Kaplan-Meier survival curves with the log-rank test used to estimate the equality of survival between patients with R0 and R1 resections.

Results

In total 191 patients were included, of whom 87 (45.5%) hade R0 resections and 104 (54.5%) were R1 resections. There were no significant differences in demographic characteristics such as age (p=0.5186), gender (p=0.146) and morbidity (p=0.947). The location of tumour and operative procedure also did not differ between R0 and R1 resections. There were however significant differences in the size of tumour, median (IQR) 26 (20-36.5) mm in R0 and 30 (25-40) mm in R1 resections and the total number of lymph nodes excised 12 (8-16) vs 15 (11-19), p=0.0049 in R0 and R1 resections respectively. The total positive lymph nodes were also higher in R1 resection with 2 (1-5) nodes compared with 0 (0-2) nodes, p=0.0001. The overall median survival was shorter after R1 resections [1.53 years (0.67-2.72) v 2.40 years (1.15-4.85), p=0.0046].

Conclusion

The tumour margin status directly impacts overall survival in patients with pancreatic cancer.
O172 Room for improvement: a multi-centre audit of our current compliance with surgical antibiotic prophylaxis guidelines in Ireland
Authors: Giblin K , Hill G , Naana O , Dowling G , Stevens N , Hill A , O’Donnell S
Published: May 2023

Introduction

In 2017, a national point prevalence study in Ireland showed low compliance with Surgical Antibiotic Prophylaxis (SAP) duration, with 70% of prescriptions exceeding recommended duration. We hypothesise that there has been little improvement since then and we aim to define our compliance issues more broadly than duration alone.

Methods

To assess compliance with SAP guidelines at a locally, a multi-site audit was conducted over a 14-day period in July 2022. Data was collected at one major, public hospital and one private hospital, both in the Dublin region. Procedures performed in an operating theatre from all surgical specialties were audited.

Results

A total of 303 procedures were audited across both sites with 165 public and 138 private included. Overall, compliance with local SAP guidance, according to indication, duration and agent was present in 72 patients (23.7%). Performance in both centres was similar (22% public versus 26% private). Of patients in whom SAP was indicated, all 182 (100%) received it. 91 patients (30%), had no indication for SAP. 19 patients (21.1%) still received SAP despite having no indication. Antibiotic duration surpassed 48 h in 58 (25%) procedures, with 40 (17.5%) receiving antibiotic prophylaxis for more than 6 days. Compliance with appropriate agent recommendation was 43.5%.

Conclusion

Compliance with SAP guidance is low. Despite contrasting work processes in public versus private settings, compliance with SAP guidelines are similar. Work is currently underway to identify barriers to compliance in order to implement quality improvement initiatives and to address this.
P01 Mentorship in United Kingdom plastic surgery
Authors: Campos M , Brady C , Nikkhah D
Published: May 2023

Introduction

A cornerstone of the Halstedian model of surgical training is a reliance on mentors to support and guide trainees in taking on increasing levels of responsibility. In the UK, however, there are significant barriers to effective mentorship which are affecting the quality of training and the satisfaction of trainees, with 85% of UK Plastic Surgery trainees reporting they do not have access to a mentoring service.

Methods

A round robin brainstorming session at the Royal Free Hospital Plastic Surgery department brought together clinicians ranging from foundation year doctors to consultants. The barriers to effective mentorship and potential solutions were discussed.

Results and Conclusion

Key barriers identified included the fragmented nature of training, with short rotations of -12 months, and the non-run-through nature of training leading to the loss of motivated trainees at each stage of competition. Proposed solutions included a transition to run-through training, with smaller deaneries allowing trainees to progress within a handful of units, increasing stability, satisfaction and mentorship. This could also be achieved by expanding the number of academic trainees, with guaranteed national training numbers and greater levels of mentorship from academic supervisors. Another proposal was a transition to the “old-school-firm style workforce”, with consultants allocated their own registrar, core trainee and foundation year doctor –promoting continuity of care, collaboration and mentorship. Finally, a nationwide mentorship scheme was postulated, with consultants supporting registrars who subsequently support junior trainees. Such a scheme should be driven by a national organisation such as BAPRAS, standardising its reaching to all UK units.
P10 Do chloroquine and hydroxychloroquine have a role as radiosensitisers in the treatment of cancer? A systematic review
Authors: Chohan M S , Goyal K , Fok M , Hill R , Kler A , Vimalachandran D
Published: May 2023

Introduction

Radiotherapy remains a mainstay treatment for many cancers often prior to surgery. Radiosensitisers are chemical or pharmaceutical agents that can enhance the effect of radiotherapy on tumour cells and can potentially de-escalate treatments including the need for surgery. Chloroquine (CQ) and Hydroxychloroquine (HCQ) are used as anti-inflammatory and anti-malarial agents but have shown to be promising radio sensitising agents. This systematic review assesses their role as radiosensitisers for the treatment of cancer and explored both pre-clinical and clinical trial evidence.

Methods

Studies that reported the use of CQ or HCQ as a radiosensitiser as either neoadjuvant or adjuvant therapy were identified via systematic review. It was conducted in accordance with PRISMA guidelines (PROSPERO: CRD42022329779). Five databases were searched for articles.

Results

30 papers were selected for review following our screening process. In 6 of the 8 clinical studies, CQ showed disease regression or increased overall survival for patients who were treated with a combination of radiotherapy and CQ. One study did not show any improvement in patient outcomes for HCQ. Most studies were performed for glioblastoma multiforme. 2 of the 3 in vitro/in vivo studies illustrated CQ as a viable radiosensitiser showing reduced tumour growth. However, multiple clinical trials were terminated due to poor patient accrual.

Conclusion

There are a limited number of preclinical and clinical trials investigating CQ and HCQ as radiosensitisers. There is evidence to suggest CQ may have a role as a radiosensitiser but there needs to be a call for more preclinical and clinical evidence.
Bi-allelic variants of FILIP1 cause congenital myopathy, dysmorphism and neurological defects
Authors: Roos Andreas , van der Ven Peter F M , Alrohaif Hadil , Kölbel Heike , Heil Lorena , Della Marina Adela , Weis Joachim , Aßent Marvin , Beck-Wödl Stefanie , Barresi Rita , Töpf Ana , O’Connor Kaela , Sickmann Albert , Kohlschmidt Nicolai , El Gizouli Magdeldin , Meyer Nancy , Daya Nassam , Grande Valentina , Bois Karin , Kaiser Frank J , Vorgerd Matthias , Schröder Christopher , Schara-Schmidt Ulrike , Gangfuss Andrea , Evangelista Teresinha , Röbisch Luisa , Hentschel Andreas , Grüneboom Anika , Fuerst Dieter O , Kuechler Alma , Tzschach Andreas , Depienne Christel , Lochmüller Hanns
Published: May 2023

Filamin-A-interacting protein 1 (FILIP1) is a structural protein that is involved in neuronal and muscle function and integrity and interacts with FLNa and FLNc. Pathogenic variants in filamin-encoding genes have been linked to neurological disorders (FLNA) and muscle diseases characterized by myofibrillar perturbations (FLNC), but human diseases associated with FILIP1 variants have not yet been described. Here, we report on five patients from four unrelated consanguineous families with homozygous FILIP1 variants (two nonsense and two missense).

Functional studies indicated altered stability of the FILIP1 protein carrying the p.[Pro1133Leu] variant. Patients exhibit a broad spectrum of neurological symptoms including brain malformations, neurodevelopmental delay, muscle weakness and pathology and dysmorphic features. Electron and immunofluorescence microscopy on the muscle biopsy derived from the patient harbouring the homozygous p.[Pro1133Leu] missense variant revealed core-like zones of myofibrillar disintegration, autophagic vacuoles and accumulation of FLNc. Proteomic studies on the fibroblasts derived from the same patient showed dysregulation of a variety of proteins including FLNc and alpha-B-crystallin, a finding (confirmed by immunofluorescence) which is in line with the manifestation of symptoms associated with the syndromic phenotype of FILIP1opathy.

The combined findings of this study show that the loss of functional FILIP1 leads to a recessive disorder characterized by neurological and muscular manifestations as well as dysmorphic features accompanied by perturbed proteostasis and myopathology.
Using racial discourse communities to audit personalization algorithms
Authors: Stoldt Ryan , Maragh-Lloyd Raven , Havens Tim , Ekdale Brian , High Andrew C
Published: May 2023

Personalization algorithms are the information undercurrent of the digital age. They learn users’ behaviors and tailor content to individual interests and predicted tastes. These algorithms, in turn, categorize and represent these users back to society—culturally, politically, and racially. Researchers audit personalization algorithms to critique the ways bias is perpetuated within these systems. Yet, research examining the relationship between personalization algorithms and racial bias has not yet contended with the complexities of conceptualizing race. This article argues for the use of racialized discourse communities within algorithm audits, providing a way to audit algorithms that accounts for both the historical and cultural influences of race and its measurement online.
Efficacy of chemotherapies for unresectable extramammary Paget disease: a single-centre retrospective study
Authors: Wada Shogo , Ogata Dai , Nakano Eiji , Namikawa Kenjiro , Yamazaki Naoya
Published: May 2023

Background

Extramammary Paget disease (EMPD) is a cutaneous neoplasm that can metastasize to the lymph nodes and distant organs, resulting in a poor prognosis. For unresectable distant metastases of EMPD, no consensus has been reached regarding optimal chemotherapy owing to a lack of data.

Objectives

To evaluate the efficacy of three regimens: docetaxel (DTX) monotherapy; combination therapy with 5-ﬂuorouracil, epirubicin, carboplatin, vincristine and mitomycin C (FECOM); and tegafur (S-1) monotherapy.

Methods

This single-centre retrospective study included 32 patients diagnosed with unresectable EMPD and treated with chemotherapy between 2002 and 2022 at the National Cancer Center Hospital in Japan. Patient characteristics, responses to treatment and survival data were evaluated for each of the first-line therapies.

Results

Among the 17 patients who received DTX monotherapy, the response rate (RR) and disease control rate (DCR) were 47% and 77%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 12.3 months [95% confidence interval (CI) 6.1–26.6] and 19.2 months (95% CI 8.5–not reached), respectively. Among the 11 patients who received combination FECOM chemotherapy, the RR and DCR were 55% and 64%, respectively. The median PFS and OS were 6.8 months (95% CI 3.5–not reached) and 13.4 months (95% CI 8.6–21.3), respectively. Among the four patients who received S-1 monotherapy, the RR and DCR were 0% and 25%, respectively. The median PFS and OS were 5.4 months (95% CI 2.3–not reached) and 12.5 (95% CI 2.3–not reached) months, respectively.

Conclusions

Further investigations with prospective analysis are required to confirm these findings.
Activation of the aryl hydrocarbon receptor inhibits the development of experimental autoimmune pancreatitis through IL-22-mediated signaling pathways
Authors: Kamata Ken , Hara Akane , Minaga Kosuke , Yoshikawa Tomoe , Kurimoto Masayuki , Sekai Ikue , Okai Natsuki , Omaru Naoya , Masuta Yasuhiro , Otsuka Yasuo , Takada Ryutaro , Takamura Shiki , Kudo Masatoshi , Strober Warren , Watanabe Tomohiro
Published: May 2023

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in hematopoietic and non-hematopoietic cells. Activation of the AhR by xenobiotics, microbial metabolites, and natural substances induces immunoregulatory responses. Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disorder of the pancreas driven by autoimmunity. Although AhR activation generally suppresses pathogenic autoimmune responses, the roles played by the AhR in AIP have been poorly defined. In this study, we examined how AhR activation affected the development of experimental AIP caused by the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Experimental AIP was induced in MRL/MpJ mice by repeated injections of polyinosinic-polycytidylic acid. Activation of the AhR by indole-3-pyruvic acid and indigo naturalis, which were supplemented in the diet, inhibited the development of experimental AIP, and these effects were independent of the activation of plasmacytoid dendritic cells producing IFN-α and IL-33. Interaction of indole-3-pyruvic acid and indigo naturalis with AhRs robustly augmented the production of IL-22 by pancreatic islet α cells. The blockade of IL-22 signaling pathways completely canceled the beneficial effects of AhR ligands on experimental AIP. Serum IL-22 concentrations were elevated in patients with type 1 AIP after the induction of remission with prednisolone. These data suggest that AhR activation suppresses chronic fibroinflammatory reactions that characterize AIP via IL-22 produced by pancreatic islet α cells.