The province of Guizhou in Southwestern China is currently one of the world's most important mercury production areas. Emissions of mercury from the province to the global atmosphere have been ...estimated to be approximately 12% of the world total anthropogenic emissions. The main objective of this study was to assess the level of contamination with Hg in two geographical areas of Guizhou province. Mercury pollution in the areas concerned originates from mercury mining and ore processing in the area of Wanshan, while in the area of Quingzhen mercury pollution originates from the chemical industry discharging Hg through wastewaters and emissions to the atmosphere due to coal burning for electricity production. The results of this study confirmed high contamination with Hg in soil, sediments and rice in the Hg mining area in Wanshan. High levels of Hg in soil and rice were also found in the vicinity of the chemical plant in Quingzhen. The concentrations of Hg decreased with distance from the main sources of pollution considerably. The general conclusion is that Hg contamination in Wanshan is geographically more widespread, due to deposition and scavenging of Hg from contaminated air and deposition on land. In Quingzhen Hg contamination of soil is very high close to the chemical plant but the levels reach background concentrations at a distance of several km. Even though the major source of Hg in both areas is inorganic Hg, it was observed that active transformation of inorganic Hg to organic Hg species (MeHg) takes place in water, sediments and soils. The concentration of Hg in rice grains can reach up to 569 μg/kg of total Hg of which 145 μg/kg was in MeHg form. The percentage of Hg as MeHg varied from 5 to 83%. The concentrations of selenium can reach up to 16 mg/kg in soil and up to 1 mg/g in rice. A correlation exists between the concentration of Se in soil and rice, indicating that a portion of Se is bioavailabile to plants. No correlation between Hg and Se in rice was found. Exposure of the local population to Hg may occur due to inhalation of Hg present in air (in particular in Hg mining area) and consumption of Hg contaminated food (in particular rice and fish) and water. Comparison of intake through these different routes showed that the values of Hg considerably exceed the USA EPA Reference Concentration (RfC) for chronic Hg exposure (RfC is 0.0004 mg/m
3) close to the emission sources. Intake of Hg through food consumption, particularly rice and fish, is also an important route of Hg exposure in study area. In general, it can be concluded that the population mostly at risk is located in the vicinity of smelting facilities, mining activities and close to the waste disposal sites in the wider area of Wanshan. In order to assess the real level of contamination in the local population, it is recommended that biomonitoring should be performed, including Hg and MeHg measurements in hair, blood and urine samples.
Imidacloprid (IMI) is at the moment the insecticide with the world’s fastest growing sales and is considered possible replacement for the widely used organophosphorus pesticide, diazinon, which is ...subject to phased revocation in many countries. In this study, biochemical, reproductive and survival parameters of the water flea (
Daphnia magna) after chronic exposure to IMI, its commercial liquid formulation Confidor SL 200 and diazinon are presented and compared. According to the lowest observed effect concentrations, diazinon is more toxic to the reproduction of
D. magna than IMI and Confidor SL 200, which exert similar toxicity. The same was observed for the survival, except that Confidor SL 200 is more toxic than IMI. In polluted aquatic environments, the actual levels of diazinon are potentially chronically hazardous to the reproduction of
D. magna (risk quotient
>
1). According to very few measured environmental levels of IMI, the latter is not expected to be chronically hazardous, unless it is accidentally spilled in a small pond. In such case, the predicted concentrations of IMI would present a potential chronic risk to
D. magna, and a potential acute risk to other aquatic invertebrates. In the future, higher environmental levels of IMI are expected due to its increasing use and physico-chemical properties. The literature survey summarized in this work suggests that further ecotoxicological studies with a broader spectrum of aquatic organisms are needed before IMI is classified as safer than currently applied pesticides.
Abstract
Background
Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a ...concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting.
Methods
A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation ECCO Collaborative Network of Exceptionally Rare case reports CONFER project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation.
Results
In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10).
Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table).
Conclusion
In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.
Abstract
Background
The European Crohn’s and Colitis Organisation (ECCO) Position Paper on Quality-of-Care (QoC) proposed essential standards on process and outcomes for units that manage patients ...with inflammatory bowel disease (IBD). The E-QUALITY taskforce investigated whether gaps between these standards and real-world practice exist.
Methods
A 74-question web survey accessible to all institutions affiliated with ECCO was developed. One delegate per institution was requested to respond. A descriptive analysis was done.
Results
From March to October 2023, 166 centres from 28 different countries replied to the survey (Fig.1).
At diagnosis, disease extent is assessed by colonoscopy in 96% and completed by small bowel (SB) evaluation in 43%. At least 2 biopsies from each segment are obtained in 55%. SB investigation for Crohn’s disease (CD) takes place in 60%. 54% of centres provide access to endoscopy with deep sedation for the majority of patients. To assess treatment response, faecal calprotectin is used in 65%, endoscopy in 54%, cross-sectional imaging for CD in 36%. In the case of primary failure of any drug, therapeutic decisions are based on objective measures of inflammation in 98%. A scheduled monitoring protocol for asymptomatic patients is followed in 42%. Patients with prolonged use of corticosteroids are being switched to a steroid-sparing treatment in 84%, but there is no protocol to track or act upon high steroid exposure in 43% of centres. 72% centres monitor metabolic bone health. Only 51% of units screen IBD patients for colorectal cancer, but screening is done with high-definition endoscopy in 92%. Chromoendoscopy with targeted biopsies is performed in only 47% units. Patients with perianal fistula are managed by combined medical and surgical approach in 67%, and reassessment by clinical and endoscopy and/or pelvic MRI is done in 62%. Laparoscopic approach for intra-abdominal surgery is used in 76%, and preoperative nutritional assessment in 62%. Patients receive therapies to prevent post-operative recurrence based on risk factors in 70%, standard endoscopy within 6-12 months after surgery is done only in 52% of centres. Although only 8% of centres lack a defined protocol to manage acute severe ulcerative colitis flares, 13% lack a standard algorithm, and 36% do not involve the surgeon in this setting from day 1. 38% of centres have a paediatric to adult transition clinic.
The main reason for not adhering to ECCO standards are difficulty of providing tests in a timely fashion in up to 83% of centres.
Conclusion
Our survey has revealed significant gaps between ECCO standards and real-world practice. These results will help ECCO improve initiatives to help institutions to provide standard QoC.
1) Fiorino et al. JCC 2020;14:1037-48
Carbon-based nanomaterials (NM) are promising candidates for a myriad of applications ranging from drug delivery to biosensing platforms. In the physiological environment, proteins can be adsorbed ...onto the surface of NM that can alter their structure and function. Little is known of the effect of NM on larger proteins and enzymes and an attempt has been made in this study to investigate the effect of carbon-based NM such as carbon black (CB), graphene oxide (GO) and fullerene (C60) on the adsorption and activity of acetylcholinesterase (AChE), a key enzyme present in brain, blood and nervous system and a suitable neurotoxicity biomarker. Experimental and computational results showed that all the carbon-based NM tested adsorb AChE but they have different effects on the catalytic activity of the enzyme. The most efficient AChE inhibitor is CB. In contrast, AChE adsorbed on the GO surface retains its native conformation and most of its activity. As compared to GO and CB, C60 was found to be an inefficient adsorbent of AChE. The distinctive adsorption pattern of NM and their inhibitory potential could be related to the surface characteristics of NM. Our studies also demonstrate the potential of GO as a substrate for immobilization of AChE.
Background:Therapeutic drug monitoring is used to guide treatment in patients treated with TNF-α inhibitors. Current bridging ELISA (bELISA), mostly used in routine analysis, cannot detect anti-drug ...antibodies (ADA) in immune complexes and differentiate between neutralizing and non-neutralizing ADA. Reporter Gene Assay (RGA), which detects only neutralizing ADA, is both costly and labour-intensive. Therefore, alternative assays are warranted to obviate these limitations.Objectives:To develop an in-house competitive ELISA (cELISA) for detection of neutralizing ADA, to compare results between four different assays for ADA detection and to propose an algorithm to assist clinicians in personalized therapeutic drug monitoring of Infliximab (IFX) and Adalimumab (ADL).Methods:Samples from 105 patients on IFX or ADL therapy (nIFX=61, nADL=44) from the Departments of Rheumatology and Gastroenterology, University Medical Centre Ljubljana, with undetectable drug levels, were tested with in-house cELISA, in-house bELISA, in-house bELISA with acetic acid dissociation (acid bELISA (1)) and RGA. cELISA was developed following the principles of RGA, briefly, diluted samples were pre-incubated with a fixed amount of IFX or ADL, linked to horseradish peroxidase. After incubation on a TNF-α plate, the reaction was detected using TMB substrate. Within and between-run imprecisions for cELISA were determined. Correlation coefficient and agreement between results from different assays were calculated.Results:Within and between-run imprecisions in cELISA met the validation criteria (<20%). We found high correlation between cELISA and RGA (anti-IFX r=0.932 (p<0.0001) and anti-ADL r=0.948 (p<0.0001)) and 100% agreement between results. cELISA also correlated with bELISA (anti-IFX r=0.663 (p=0.0002) and anti-ADL r=0.896 (p<0.0001)). Agreement between bELISA and cELISA was 79% for anti-IFX and 82% for anti-ADL samples.The more sensitive cELISA and functional RGA detect 13% (8/61) more positive samples in anti-IFX group and 18% (8/44) more samples in anti-ADL group. Acid bELISA found 3% (2/61) more positive samples in anti-IFX group and 14% (6/44) of samples in the anti-ADL group.In total, 16% (10/61) more samples in anti-IFX and 30% (13/44) more samples in anti-ADL group were confirmed having ADA. Based on our results we propose a sequential algorithm, which enables reliable, affordable and increased detection of ADA (figure 1).Figure 1Algorithm for therapeutic drug monitoring of IFX and ADL. IFX – Infliximab, ADL – Adalimumab, ADA – anti-drug antibodies, bELISA – bridging ELISA, acid bELISA – bELISA with acid dissociation, cELISA – competitive ELISA;Conclusions:cELISA and acid bELISA, together, can detect ADA in 16% more samples in anti-IFX and 30% in anti-ADL group than classical bELISA used in current practice. The proposed algorithm can assist in everyday practice and enables better evaluation of patients treated with TNF-α inhibitors.Reference1Van Stappen, et al. Drug Test Anal2017;9(2):243–7.Disclosure of Interest:None declared
Background: Therapeutic drug monitoring is used to guide treatment in patients treated with TNF-α inhibitors. Current bridging ELISA (bELISA), mostly used in routine analysis, cannot detect anti-drug ...antibodies (ADA) in immune complexes and differentiate between neutralizing and non-neutralizing ADA. Reporter Gene Assay (RGA), which detects only neutralizing ADA, is both costly and labour-intensive. Therefore, alternative assays are warranted to obviate these limitations. Objectives: To develop an in-house competitive ELISA (cELISA) for detection of neutralizing ADA, to compare results between four different assays for ADA detection and to propose an algorithm to assist clinicians in personalized therapeutic drug monitoring of Infliximab (IFX) and Adalimumab (ADL). Methods: Samples from 105 patients on IFX or ADL therapy (nIFX=61, nADL=44) from the Departments of Rheumatology and Gastroenterology, University Medical Centre Ljubljana, with undetectable drug levels, were tested with in-house cELISA, in-house bELISA, in-house bELISA with acetic acid dissociation (acid bELISA (1)) and RGA. cELISA was developed following the principles of RGA, briefly, diluted samples were pre-incubated with a fixed amount of IFX or ADL, linked to horseradish peroxidase. After incubation on a TNF-α plate, the reaction was detected using TMB substrate. Within and between-run imprecisions for cELISA were determined. Correlation coefficient and agreement between results from different assays were calculated. Results: Within and between-run imprecisions in cELISA met the validation criteria (<20%). We found high correlation between cELISA and RGA (anti-IFX r=0.932 (p<0.0001) and anti-ADL r=0.948 (p<0.0001)) and 100% agreement between results. cELISA also correlated with bELISA (anti-IFX r=0.663 (p=0.0002) and anti-ADL r=0.896 (p<0.0001)). Agreement between bELISA and cELISA was 79% for anti-IFX and 82% for anti-ADL samples. The more sensitive cELISA and functional RGA detect 13% (8/61) more positive samples in anti-IFX group and 18% (8/44) more samples in anti-ADL group. Acid bELISA found 3% (2/61) more positive samples in anti-IFX group and 14% (6/44) of samples in the anti-ADL group. In total, 16% (10/61) more samples in anti-IFX and 30% (13/44) more samples in anti-ADL group were confirmed having ADA. Based on our results we propose a sequential algorithm, which enables reliable, affordable and increased detection of ADA (figure 1). Conclusions: cELISA and acid bELISA, together, can detect ADA in 16% more samples in anti-IFX and 30% in anti-ADL group than classical bELISA used in current practice. The proposed algorithm can assist in everyday practice and enables better evaluation of patients treated with TNF-α inhibitors. Reference 1Van Stappen, et al. Drug Test Anal2017;9(2):243-7. Disclosure of Interest: None declared
Abstract
Background
There are limited data available on the course of IBD in patients with solid organ transplantation.
The aim of this ECCO CONFER study was to evaluate the trend of IBD before and ...after solid organ transplantation but liver.
Methods
This was a retrospective observational multicentre study that collected cases through the CONFER project. Patients with an established IBD diagnosis who underwent a solid organ transplantation (with the exception of liver) were eligible candidates.
Results
33 patients with solid organ transplantation (67% male; 55% CD) were collected from 12 referral centres in five different countries.
Mean age was 53 ± 16 years. 34 organs were transplanted in 33 patients. Most of the patients underwent kidney transplantation (n=27, 82%). 4 (12%) received a heart and 1 (3%) underwent lung transplantation; 1 (3%) underwent a combined heart and kidney transplant.
The mean duration of IBD was 18.4 ± 14.7 months. Clinical characteristics are summarized in Table 1.
The median follow-up after transplantation was 4.3 years (IQR 3.25 – 10.7).
7/33 patients (21.2%) experienced organ rejection, with 1 kidney retransplant.
Regarding immunosuppressive therapy, 29/33 patients (88%) were treated with tacrolimus, 25 (76%) with systemic steroids, 22 (67%) with mycophenolate mofetil, 11 (33%) with everolimus, 6 with cyclosporine (18%), 3 (9%) with thiopurines. Regarding biologics, 1 patient was treated with infliximab, 2 with adalimumab, 2 with vedolizumab, 1 with ustekinumab.
Defining a severe IBD course the need for biologic therapy or bowel resection or hospitalization, 4 patients (11.7%) had a severe disease course after transplantation versus 3 patients (9.3%) in the first 51 months of disease before transplantation (p = 0.26). Univariate analysis is reported in Table 2.
1 case of low-grade dysplasia was found 10 years after the transplantation. 1 case of colorectal cancer was found in a patient affected by CD five years after kidney transplantation. The other cases of tumours after transplantation are reported in Table 3.
The first serious infectious episode after transplantation is shown in Table 4: 17 of 33 patients (51.5%) reported at least 1 episode of serious infection.
In total 29 different serious infectious episodes after transplantation were recorded, compared to 28 episodes in the pre-transplantation period.
At the last follow-up visit, 6/33 (18.2%) patients had died: 1 due to cholangiocarcinoma, 1 amyloidosis, 1 heart failure, 1 myocardial infection (2 not available).
Conclusion
Solid organ transplantation appears to have a satisfactory course for both the transplanted organ and IBD, in terms of organ survival and IBD severity; furthermore, the use of biologics in these patients does not appear to be linked to a worse outcome.
Cellular nanovesicles (CNVs), that are shed from cells, have been recognized as promising indicators of health status. We analyzed the effect of long-distance running on concentration of CNVs, along ...with some standard blood parameters, in 27 athletes two days before and >15 hours after physical effort.
CNVs were isolated by repetitive centrifugation and washing of samples, and assessed by flow cytometry. Cholinesterase (ChE) and glutathione S-transferase (GST) activity were measured spectrophotometrically. Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) was measured with immunoturbidimetric determination and lipidogram parameters were measured by enzymatic colorimetric assay. Flow cytometry was used for blood cell count and mean platelet volume (MPV) measurement.
More than 15 hours after physical effort a decrease was found in CNVs' concentration in isolates from blood (46%; p<0.05), in ChE activity in whole blood (47%; p<0.001), in plasma (34%; p<0.01), and in erythrocyte suspension (54%; p<0.001), as well as in GST activity in erythrocyte suspension (16%; p<0.01) and in IL-6 concentration in plasma (63%; p<0.05). We found no change in GST activity in plasma and in TNF-α concentration in plasma. Correlations (>0.8; p<0.001) between CNVs' concentration and ChE activity, and GST activity, respectively, in erythrocyte suspension were found.
We found that >15 hours post-physical effort, CNVs' concentration was below the initial value, concomitant with other measured parameters: ChE and GST activity as well as IL-6 concentration, indicating a favorable effect of physical effort on health status. CNVs' concentration and ChE activity in isolates from peripheral blood proved to have potential as indicators of the response of the human body to inflammation after physical effort. Physical activity should be considered as an important factor in preparation of subjects for blood sampling in procedures focusing on CNV-containing diagnostic and therapeutic compounds.
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