The prospective validation of a scoring system to assess mucosal cleanliness during EGD.

BACKGROUND AND AIMS: Cleanliness of the mucosa of the upper GI (UGI) tract is critical for performing a high-quality EGD. The aim of this study was to validate a recently developed UGI cleanliness scale (the Polprep: Effective Assessment of Cleanliness in Esophagogastroduodenoscopy [PEACE] system) in the detection of clinically significant lesions (CSLs) in the UGI tract. METHODS: Patients who underwent a complete diagnostic EGD were prospectively enrolled from August 2021 to October 2022. The UGI tract (esophagus, stomach, and duodenum) cleanliness was scored from 0 to 3 for each segment. The primary outcomes were the detection of CSLs and PEACE scores. RESULTS: Of 995 patients enrolled from 5 centers, adequate cleanliness (AQ; all scores ≥2) was found in 929 patients. In multivariate regression analysis, AQ was associated with the number of diagnosed CSLs (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.06-3.01; P = .03). Other factors related to CSL detection were duration of EGD (OR, 1.29, 95% CI, 1.23-1.35, P < .001), male sex (OR, 1.33, 95% CI, 1.04-1.71; P = .025), and EGD indication (dyspepsia, alarm symptoms, gastritis surveillance, other indications vs GERD) (OR, 0.43 [95% CI, 0.31-0.6, P < .001], OR, 0.44 [95% CI, 0.28-0.67, P < .001], OR, 0.44 [95% CI, 0.25-0.76; P = .004], and OR, 0.44 [95% CI, 0.31-0.62; P < .001], respectively). Twenty-seven patients were diagnosed with UGI neoplasia, all in patients with adequate cleanliness of the UGI tract. CONCLUSIONS: Adequate cleanliness of the UGI tract as assessed with the PEACE system was associated with a significantly higher detection rate of CSLs during EGD. The relationship of this scale with UGI neoplasia detection warrants further investigation.

Establishment of standards for the referral of large nonpedunculated colorectal polyps: an international expert consensus using a modified Delphi process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large nonpedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

Training in basic gastrointestinal endoscopic procedures: a European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

This ESGE Position Statement provides structured and evidence-based guidance on the essential requirements and processes involved in training in basic gastrointestinal (GI) endoscopic procedures. The document outlines definitions; competencies required, and means to their assessment and maintenance; the structure and requirements of training programs; patient safety and medicolegal issues. 1: ESGE and ESGENA define basic endoscopic procedures as those procedures that are commonly indicated, generally accessible, and expected to be mastered (technically and cognitively) by the end of any core training program in gastrointestinal endoscopy. 2: ESGE and ESGENA consider the following as basic endoscopic procedures: diagnostic upper and lower GI endoscopy, as well as a limited range of interventions such as: tissue acquisition via cold biopsy forceps, polypectomy for lesions ≤ 10 mm, hemostasis techniques, enteral feeding tube placement, foreign body retrieval, dilation of simple esophageal strictures, and India ink tattooing of lesion location. 3: ESGE and ESGENA recommend that training in GI endoscopy should be subject to stringent formal requirements that ensure all ESGE key performance indicators (KPIs) are met. 4: Training in basic endoscopic procedures is a complex process and includes the development and acquisition of cognitive, technical/motor, and integrative skills. Therefore, ESGE and ESGENA recommend the use of validated tools to track the development of skills and assess competence. 5: ESGE and ESGENA recommend incorporating a multimodal approach to evaluating competence in basic GI endoscopic procedures, including procedural thresholds and the measurement and documentation of established ESGE KPIs. 7: ESGE and ESGENA recommend the continuous monitoring of ESGE KPIs during GI endoscopy training to ensure the trainee's maintenance of competence. 9: ESGE and ESGENA recommend that GI endoscopy training units fulfil the ESGE KPIs for endoscopy units and, furthermore, be capable of providing the dedicated personnel, infrastructure, and sufficient case volume required for successful training within a structured training program. 10: ESGE and ESGENA recommend that trainers in basic GI endoscopic procedures should be endoscopists with formal educational training in the teaching of endoscopy, which allows them to successfully and safely teach trainees.

Multi-Elemental Analysis of Hair and Fingernails Using Energy-Dispersive X-ray Fluorescence (ED XRF) Method Supported by Inductively Coupled Plasma Mass Spectrometry (ICP MS).

This work compared the multi-element analysis of human hair and nails using inductively coupled plasma mass spectrometry (ICP MS) with an easy, fast, cheap, non-destructive method using energy-dispersive x-ray fluorescence (ED XRF). The ICP MS-based method was more sensitive (over 30 elements could be quantified) and costly (requiring more time, samples, and chemicals). The EDX-based method required laboratory and certified reference materials made of hair for instrument calibration. It was less sensitive (16 elements could be quantified: S, Si, Ca, Br, Fe, Cu, Cr, Mg, Si, K, Mn, Ni, Zn, Se, Sr, Pb), but it allowed us to replace troublesome grinding with the dissolution of keratin-based material with an alkalic agent (tetramethylammonium hydroxide, TMAH) and the formation of stable-for-days pellets. This method is simple, enables automation, and, due to the modification of wells in the autosampler of the EDX system via the immersion of home-designed inserts, it requires smaller amounts of biological material and binder (down to 70 mg instead of 500 mg required by commercially available instrument) to perform analysis. It was concluded that the EDX-based method offers complementary selectivity and sensitivity to ICP MS with the possibility of sample reuse for further analysis.

Accuracy in Polyp Size Measurement Among Surgeons, Gastroenterologists, Trainees, and Experts: A Prospective Video-Based Study.

INTRODUCTION: Polyp size determination plays an important role in endoscopic decision making and follow-up determination. However, there is a lack of knowledge of endoscopist accuracy for polyp sizing and efficacy of available tools for size measurement. Our aim was to compare the accuracy of visual assessment, snare, forceps, and virtual scale endoscope (VSE) in estimating polyp size among a diverse group of endoscopists. METHODS: We conducted a prospective video-based study. One hundred twenty polyps measured and recorded along with all available measurement tools were randomized to visual assessment, snare, forceps, or VSE group. Eleven endoscopists conducted video-based measurement using the randomized measurement tool. Primary outcome was relative accuracy in polyp size measurement compared with caliper measurement immediately postresection. RESULTS: One thousand three hundred twenty measurements were performed. VSE had statistically significantly higher relative accuracy when compared to forceps (79.3 vs 71.3%; P < 0.0001). Forceps had statistically significantly higher relative accuracy when compared to visual assessment (71.3 vs 63.6%; P = 0.0036). There was no statistically significant difference when comparing visual assessment and snare-based measurements (63.6 vs 62.8%; P = 0.797). Overall, 21.5% of polyps >5 mm were misclassified as ≤5 mm and 17.3% of polyps ≥10 mm were misclassified as <10 mm. VSE had the lowest percentage of polyps >5 mm misclassified as ≤5 mm (2.6%), polyps ≤5 mm misclassified as >5 mm (5.1%), and polyps <10 mm misclassified as ≥10 mm (1.7%). DISCUSSION: Visual size estimation of polyps is inaccurate independently of training level, sex, and specialty. Size measurement accuracy can be improved using forceps and yields the highest relative accuracy when an adaptive scale technology is used.

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Phosphorylation of Thymidylate Synthase and Dihydrofolate Reductase in Cancer Cells and the Effect of CK2α Silencing.

Our previous research suggests an important regulatory role of CK2-mediated phosphorylation of enzymes involved in the thymidylate biosynthesis cycle, i.e., thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). The aim of this study was to show whether silencing of the CK2α gene affects TS and DHFR expression in A-549 cells. Additionally, we attempted to identify the endogenous kinases that phosphorylate TS and DHFR in CCRF-CEM and A-549 cells. We used immunodetection, immunofluorescence/confocal analyses, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), in-gel kinase assay, and mass spectrometry analysis. Our results demonstrate that silencing of the CK2α gene in lung adenocarcinoma cells significantly increases both TS and DHFR expression and affects their cellular distribution. Additionally, we show for the first time that both TS and DHFR are very likely phosphorylated by endogenous CK2 in two types of cancer cells, i.e., acute lymphoblastic leukaemia and lung adenocarcinoma. Moreover, our studies indicate that DHFR is phosphorylated intracellularly by CK2 to a greater extent in leukaemia cells than in lung adenocarcinoma cells. Interestingly, in-gel kinase assay results indicate that the CK2α' isoform was more active than the CK2α subunit. Our results confirm the previous studies concerning the physiological relevance of CK2-mediated phosphorylation of TS and DHFR.

Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project).

BACKGROUND: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. METHODS: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. RESULTS: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. CONCLUSION: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale.

BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

Attomole-per Cell Atomic Mass Spectrometry Measurement of Platinum and Gold Drugs in Cultured Lung Cancer Cells.

In this study, we developed a strategy to determine atto- and femtomolar amounts of metal ions in lysates and mineralizates of cells (human non-small-cell lung carcinoma (NSCLC, A549) and normal lung (MRC-5)) exposed to cytotoxic metallo-drugs: cisplatin and auranofin at concentrations close to the half-maximal inhibitory drug concentrations (IC50). The developed strategy combines data obtained using biological and chemical approaches. Cell density was determined using two independent cell staining assays using trypan blue, calcein AM/propidium iodide. Metal concentrations in lysed and mineralized cells were established employing a mass spectrometer with inductively coupled plasma (ICP-MS) and equipped with a cross-flow nebulizer working in aspiration mode. It allowed for detecting of less than 1 fg of metal per cell. To decrease the required amount of sample material (from 1.5 mL to ~100 µL) without loss of sensitivity, the sample was introduced as a narrow band into a constant stream of liquid (flow-injection analysis). It was noticed that the selectivity of cisplatin accumulation by cells depends on the incubation time. This complex is accumulated by cells at a lower efficiency than auranofin and is found primarily in the lysate representing the cytosol. In contrast, auranofin interacts with water-insoluble compounds. Despite their different mechanism of action, both metallo-drugs increased the accumulation of transition metal ions responsible for oxidative stress.

On the Track of New Endoscopic Alternatives for the Treatment of Selected Gastric GISTs-A Pilot Study.

Background and Objectives: GISTs (Gastrointestinal stromal tumors) are the most common mesenchymal gastrointestinal tract tumours and are mainly located in the stomach. Their malignant potential depends on size, location, and type. Endoscopic techniques are a less invasive modality for patients not eligible for surgery. ESD (endoscopic submucosal dissection) is mainly used for the removal of smaller GISTs, with intraluminal growth and a more superficial location. Thus, R0 resection capability in some cases may be not sufficient, limited by tumour size, location in the gastric wall, and its connection level with the muscularis propria. In such cases, an endoscopic full-thickness resection can become a new alternative. In this retrospective pilot study, we evaluated ESD and hybrid resection techniques in terms of safety, efficacy, and disease recurrence for selected types of gastric GISTs. Materials and Methods: A retrospective comparison was conducted in a group of patients who underwent ESD or a hybrid technique combining endoscopic resection with endoscopic suturing using the OverStitch system (HT) for type II or III gastric GISTs. A total of 21 patients aged 70 ± 8 years underwent endoscopic resection. Seventeen lesions were treated with ESD and four with the HT. Results: R0 resection was achieved in all patients treated using HT (type III lesions) and in 53% of those treated with ESD (p = 0.08). None of the type III lesions treated with ESD were excised with R0. Lesions treated with R0 ESD resections were significantly smaller (1.76 ± 0.35 cm) than those with R1 ESD resections (2.39 ± 0.40 cm) (p < 0.01). The mean lesion size treated with the HT was 2.88 ± 0.85 cm. Conclusions: HT may be a new resection modality for large gastric GISTs with high muscularis propria connection grades. Further studies are required to evaluate its safety and efficacy and to form precise inclusion criteria for endoscopic resection techniques.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Secreted Metabolome of Human Macrophages Exposed to Methamphetamine.

Macrophages comprise a major component of the human innate immune system that is involved in maintaining homeostasis and responding to infections or other insults. Besides cytokines and chemokines, macrophages presumably influence the surrounding environment by secreting various types of metabolites. Characterization of secreted metabolites under normal and pathological conditions is critical for understanding the complex innate immune system. To investigate the secreted metabolome, we developed a novel workflow consisting of one Reverse Phase (RP) C18 column linked in tandem with a Cogent cholesterol-modified RP C18. This system was used to compare the secreted metabolomes of human monocyte-derived macrophages (hMDM) under normal conditions to those exposed to methamphetamine (Meth). This new experimental approach allowed us to measure 92 metabolites, identify 11 of them as differentially expressed, separate and identify three hydroxymethamphetamine (OHMA) isomers, and identify a new, yet unknown metabolite with a m/z of 192. This study is the first of its kind to address the secreted metabolomic response of hMDM to an insult by Meth. Besides the discovery of novel metabolites secreted by macrophages, we provide a novel methodology to investigate metabolomic profiling.

Pre-procedural abnormal function of von Willebrand Factor is predictive of bleeding after surgical but not transcatheter aortic valve replacement.

Both transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have been proven to effectively correct von Willebrand Factor (vWF) pathologies, however there is limited data simultaneously comparing outcomes of both approaches. We prospectively enrolled patients with severe aortic stenosis referred for TAVI (n = 52) or SAVR (n = 48). In each case, vWF antigen (vWF:Ag), vWF activity (vWF:Ac) and activity-to-antigen (vWF:Ac/Ag) ratio were assessed at baseline, 24 h and 72 h after procedure. VWF abnormalities were defined as reduced vWF:Ac/Ag ratio (< 0.8). Bleeding events in both arms were classified according to Valve Academic Research Consortium (VARC-2) definitions. Overall, there was no difference between patients referred for TAVI and SAVR in vWF:Ac (1.62 ± 0.52 vs 1.71 ± 0.64; p = 0.593), vWF:Ag (1.99 ± 0.81 vs 2.04 ± 0.81; p = 0.942) or vWF:Ac/Ag ratio (0.84 ± 0.16 vs 0.85 ± 0.12; p = 0.950). Pathological vWF:Ac/Ag ratio was found in 20 (38%) TAVI and 15 (31%) SAVR patients (p = 0.407). Normalization of vWF:Ac/Ag ratio at day 3 after procedure was achieved in 19 (95%) TAVI and 13 (87%) SAVR patients (p = 0.439). Similar prevalence of major or life-threatening bleedings (MLTB) after TAVI and SAVR in entire groups was observed (19% vs. 23%, p = 0.652). VWF abnormalities were associated with higher incidence of MLTB in SAVR (53% vs 9%, p < 0.001), but not TAVI (15% vs. 22%, p = 0.132). Accordingly, in receiver-operating characteristic curve analysis vWF:Ac/Ag ratio < 0.8 showed significant sensitivity and specificity for predicting MLTB in SAVR group (AUC 0.735, 95% CI 0.538-0.931, p = 0.019). We proved that abnormal function of vWF is corrected successfully after both TAVI and SAVR, but vWF abnormalities are predictive of MLTB only in surgical patients.

Seroprevalence of IgG antibodies against measles in a selected Polish population - do we need to be re-vaccinated?

INTRODUCTION: Measles is highly contagious, but preventable viral disease. Its outbreaks appear all over the world, and decreasing herd immunity excludes its elimination. High levels of IgG antibodies against a virus efficiently protects against infection. AIM OF THIS STUDY: To assess the seroprevalence of anti-measles IgG in the serum of patients at different age levels tested for measles IgG at our laboratory. MATERIAL AND METHODS: The study was conducted from March to June of 2019. Retrospective analysis included results for measles-specific IgG from 364 tested patients. The age of enrolled subjects ranged from four months to 101 years, with a median age of 46, and a mean age of 43 ±18. Quantification of anti-measles IgG was performed using indirect chemiluminescence immunoassays on the DiaSorin Liaison® automated analyzer. RESULTS: Our results showed a seropositivity ratio of 78.02%. The lowest number of seropositive subjects was in the group of infants (0-1 years old), with a ratio of 53.85%, and the group of adults of 19-38 years old at 55.68%. The group of the oldest patients (70-101 years old) had the highest ratio of seropositive subjects (100%), while adults of 60-69 years old had a seropositivity ratio of 97.22%. CONCLUSIONS: These data suggest that the group of young adults who were vaccinated with one or two doses of MMR vaccine in childhood are the most susceptible for infection, and when working in contact with other people, should be re-vaccinated for protection against measles.