bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and analysis of indicator and pathogenic bacteria in conventional and organic fruits and vegetables sold in retail markets
Authors: Srisamran Jutanat , Atwill Edward R , Chuanchuen Rungtip , Jeamsripong Saharuetai
Published: February 2022

Produce-associated food-borne outbreaks have been increasingly implicated as the significant proportion of the annual incidence of food-borne illness worldwide. The objectives of this study were to determine the concentrations of indicator bacteria and the presence of Salmonella spp., Shigella spp., Escherichia coli (E. coli) O157:H7, and Listeria monocytogenes (L. monocytogenes), and to characterize predictors associated with Salmonella contamination of retail produce from fresh markets and supermarkets in Bangkok, Thailand. A total of 503 samples were collected during May 2018 and February 2019, comprised of sweet basil, spring onion, coriander, cabbage, lettuce, cucumber, and tomato, with conventional items from fresh open-air markets (n=167), conventional items from supermarkets (n=168), and organic items from supermarkets (n=168). The overall prevalence in these 503 items for fecal coliforms and E. coli was 84.3% and 71.4%, with mean concentrations (±standard deviation) of fecal coliforms and E. coli being (3.0×105±1.3×106) most probable number (MPN)/g and (1.8×105±1.1×105) MPN/g, respectively. The concentrations of fecal coliforms and E. coli were higher in produce sampled from fresh open-air markets than produce from supermarkets; similarly, these bacterial indicators were higher from produce grown under conventional methods than certified organic produce. The prevalence of Salmonella and Shigella was 4.8% and 0.4%, respectively, but no positives were found for E. coli O157:H7 and L. monocytogenes. The predominant Salmonella serovar was Stanley (30.8%). Based on logistic regression, the odds of Salmonella contamination were significantly (P<0.05) higher during the rainy versus dry season, produce grown using conventional versus organic agriculture, sweet basil versus other commodities, and using ice tank versus dry refrigeration for overnight retail storage. This study indicated that fruits and vegetables are important sources of microbial contamination. Hence, monitoring and surveillance of pathogen contamination to produce is needed to strengthen food safety.
Exploring genetic variation and population structure in a threatened species, Noturus placidus, with whole-genome sequence data
Authors: Whitacre Lynsey K , Wildhaber Mark L , Johnson Gary S , Durbin Harly J , Rowan Troy N , Tribe Peoria , Schnabel Robert D , Mhlanga-Mutangadura Tendai , Tabor Vernon M , Fenner Daniel , Decker Jared E
Published: February 2022

The Neosho madtom (Noturus placidus) is a small catfish, generally less than 3 inches in length, unique to the Neosho-Spring River system within the Arkansas River Basin. It was federally listed as threatened in 1990, largely due to habitat loss. For conservation efforts, we generated whole-genome sequence data from 10 Neosho madtom individuals originating from 3 geographically separated populations to evaluate genetic diversity and population structure. A Neosho madtom genome was de novo assembled, and genome size and content were assessed. Single nucleotide polymorphisms were assessed from de Bruijn graphs, and via reference alignment with both the channel catfish (Ictalurus punctatus) reference genome and Neosho madtom reference genome. Principal component analysis and structure analysis indicated weak population structure, suggesting fish from the 3 locations represent a single population. Using a novel method, genome-wide conservation and divergence between the Neosho madtom, channel catfish, and zebrafish (Danio rerio) was assessed by pairwise contig alignment, which demonstrated that genes important to embryonic development frequently had conserved sequences. This research in a threatened species with no previously published genomic resources provides novel genetic information to guide current and future conservation efforts and demonstrates that using whole-genome sequencing provides detailed information of population structure and demography using only a limited number of rare and valuable samples.
The impact of tunnels on conflicts in the Middle East
Authors: Steenkamp Christina
Published: February 2022

The battlefields in the contemporary conflicts in the Middle East are multi-level conflicts. They take place in the air and on the ground, but an important and often overlooked dimension of these conflicts is found under the surface. This article recognizes the usefulness of political geography's ‘volumetric turn’ as it examines the use of tunnels in conflict, particularly in the post-2001 conflicts in the Middle East. It asks questions about who uses tunnels, for which purposes and about the impact of tunnels on conflicts. It proceeds to show how tunnels are used by a range of actors (including states, insurgents, civilians and organized crime groups) for various, often overlapping purposes (including offensive, defensive and smuggling/economic purposes). The article argues that tunnels impact on conflicts by benefiting the weaker side in asymmetrical warfare, by directly affecting states’ military strategy, by either generating or challenging political legitimacy and lastly, by becoming central to the economic survival of civilians in conflict. A greater recognition of the subterranean dimension of contemporary Middle Eastern conflicts will provide a more nuanced understanding of the duration, intensity and consequences of these wars.
Liberal modernity and the classical realist critique of the (present) international order
Authors: Karkour Haro L
Published: February 2022

In their critique of liberal modernity, classical realists theorized its consequence for the heightened sense of insecurity and powerlessness of the individual on the one hand, and the individual's identification with extreme nationalism and violence on the other. This became the challenge posed by liberal modernity in the post-1945 international order. The article argues that the present international order is an extension of the post-1945 order that never resolved this challenge. While the ‘embedded’ form of liberalism that lasted until the early 1970s made social compromises that mitigated the socio-economic insecurities of the individual in liberal modernity, it did not resolve this challenge. The later advancement of neo-liberalism only further intensified it. The article thus critiques existing debates that downplay the challenge of liberal modernity in their analyses of the crisis of the present international order. It concludes that if the present international order is to be put on more stable and peaceful grounds, it requires a more radical break from its post-1945 and post-Bretton Woods past: a break that does not simply call for ‘leadership’ or ‘offshore balancing’ but addresses the psycho-social needs of the individual in liberal modernity.
Solutions to world-wide fisheries problems are mostly local or regional
Authors: Kearney Bob , Hilborn Ray
Published: February 2022

The benefits of multinational agreements that address global problems, such as climate change, must not be diminished by uncritical acceptance that the action that is necessary to address all widespread problems, such as overfishing, is common, globally. Evidence-based identification of the nature and cause of threats to marine ecosystems is the essential first step in effective ocean management. Action that targets each threat across as much as possible of the area in which it arises, which may be entirely different from where it manifests, is the second. These concepts are not new, however, The High Level Panel for a Sustainable Ocean Economy (HLOP) has given them increased impetus by mandating that its signatories, in addressing priority marine issues, which may vary from country to country and collectively be of global importance, must begin with addressing threats in 100% of national waters. The successful management of the world's biggest tuna resources across 50 million km2 of the Central and Western Pacific is put forward as an example of how an initial commitment to a single shared fisheries resource assessment program can provide the foundation for consensus amongst more than 40 countries on the sharing of the benefits of managed access to widespread oceanic resources.
First in human surgical implantation of a leadless pacemaker on the epicardial portion of the right atrial appendage in a patient with a cardiac electronic devices mediated dermatitis
Authors: Eltsov Ivan , Sorgente Antonio , de Asmundis Carlo , La Meir Mark
Published: February 2022

A 33-year-old woman with Sick Sinus Node syndrome and persistent atrial fibrillation underwent a Maze IV procedure in order treat atrial fibrillation and concomitant atrial epicardial implantation of a leadless pacemaker to manage her sinus node insufficiency. Last option has been chosen due to rare pocket complication after previous classic dual-chamber pacemaker implantation.
Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience
Authors: Fox Henrik , Gyoten Takayuki , Rojas Sebastian V , Lauenroth Volker , Günther Sabina , Schramm René , Gummert Jan F , Morshuis Michiel
Published: February 2022

OBJECTIVES

Pump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol.

METHODS

Outcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application.

RESULTS

A total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8–22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication.

CONCLUSIONS

Despite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.
Simple smoke ventilation method for uniportal video-assisted thoracoscopic surgery
Authors: Mizukami Yasushi , Maki Ryunosuke , Adachi Hirofumi
Published: February 2022

Fogging of the thoracoscopic lens affects a surgeon’s ability to maintain a clear operating field. In uniportal video-assisted thoracoscopic surgery, the thoracoscopic lens tends to fog when the surgeon does not hold a suction instrument. Thus, a suction instrument needs to be held by the surgeon’s nondominant hand to remove surgical smoke, mist, and moisture. Here, we describe a simple, easy and cost-effective surgical smoke ventilation technique for uniportal video-assisted thoracoscopic surgery using a suction catheter to solve the problem. We present this technique and comment on its advantages, including decreased cost and improved surgical visualization.
Optimal reinsurance pricing, risk sharing and investment strategies in a joint reinsurer-insurer framework
Authors: Yang Peng , Chen Zhiping
Published: February 2022

We investigate the reinsurance contract and investment strategy problem between an insurer and a reinsurer under the continuous-time framework. For the reinsurance contract design, the joint interests of the insurer and the reinsurer are considered. That is, the insurer determines the claim risk sharing strategy, and the reinsurer determines the reinsurance price. The insurer and the reinsurer can invest in the common risk-free asset and different risky assets to increase their respective wealths. The competition between the insurer and the reinsurer is quantified through the relative performance. Both the insurer and the reinsurer aim at maximizing the expected value of the terminal pay-off while minimizing its variance. By using the stochastic optimal control technique, we derive analytically the optimal time-consistent investment strategy and obtain the optimal reinsurance contract. Finally, the influences of model parameters on the optimal reinsurance contract and time-consistent investment strategy are examined through numerical experiments.
Radiologic and Pathologic Correlation for Angiolipomas of the Breast
Authors: Babiss Emily , Cheng Esther , Mema Eralda
Published: February 2022

Angiolipomas of the breast are rare; however, they are an important entity for the radiologist who determines radiologic-pathologic concordance and recommends appropriate management. They can present as a palpable concern, prompting diagnostic workup, or can be detected on screening breast examinations. They often present as a circumscribed low-density mass on mammography, which is hyperechoic on sonography; associated fibrin thrombi can produce soft tissue density and/or hypoechoic foci that appear hypointense on T1-weighted MRI. Due to the nonspecific radiographic appearance, tissue sampling is often required for definitive diagnosis. Pathologically, angiolipomas can be difficult to distinguish from angiosarcomas; however, scattered microthrombi in small blood vessels are a typical feature of angiolipomas. Generally, in the setting of radiologic-pathologic concordance, angiolipomas do not need to be excised and can be followed clinically when palpable. Surgical excision can be pursued when certain high-risk features, such as nuclear enlargement, an infiltrative pattern, endothelial mitoses, and a high proliferation rate, are present in the core-needle biopsy specimen.
A4 HELMINTH-DERIVED METABOLITES INDUCE A TOLEROGENIC PROFILE IN DENDRITIC CELLS AND ALLEVIATE EXPERIMENTAL COLITIS
Authors: Malacco N O , Siciliani E A , Madrigal A G , Cestari I , Jardim A , Stevenson M , Lopes F
Published: February 2022

Background

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by abdominal pain, bloody diarrhea, fatigue, weight loss, and diminished quality of life. The morbidity associated with IBD is a result of loss of tolerance towards the gastrointestinal commensal microbiota. The high incidence of IBD in Western societies is inversely correlated with the low incidence of intestinal helminth parasite infections, potentially due to the ability of the helminth parasite to induce tolerance by inducing tolerogenic dendritic cells (tolDC) polarization. Although macromolecules from helminth such as proteins and polysaccharides have been shown to polarize tolDCs, to characterize a novel pathway, in this study we focused on small molecules such as metabolites in the helminth secretome. We hypothesized that helminth-derived metabolites (HDMs) polarize DCs towards a tolerogenic phenotype, which alleviates colitis.

Aims

To evaluate and characterize the tolerogenic response induced by HDMs in DCs, and its ability to alleviate colitis.

Methods

Heligmosomoides polygyrus worms were culture for 24 h and HDMs were isolated from conditioned media by chromatography. Bone marrow dendritic cells (BMDCs) were differentiated with GM-CSF for 8 days and then incubated with HDM for 4 h before LPS stimulation for 20 h. Cytokine secretion was measured by ELISA. The transcriptome of DCs treated with HDMs was assessed by RNAseq. Colitis was induced by giving 3% DSS in drinking water for 5 days followed by 3 days of tap water. The anti-colitic effect of HDMs was assessed by daily treatment with HDM or DCs treated with HDM in the 3 days of tap water.

Results

Pre-treatment with HDM decreased LPS-induced TNF and increased IL-10 release by BMDCs, compared to control BMDCs. Colitic mice treated with HDM presented lower disease activity scores, less colon shortening, decreased weight loss, and healthier histopathology compared to vehicle-treated colitic mice. Importantly, there was an increased frequency of CD11c+ CD103+ DCs in the colon of HDM-treated mice, suggesting that HDM alleviates colitis by increasing the abundance of tolDCs in the colon. Adoptive transfer of HDM-treated DCs also reduced the severity of colitis compared with vehicle-treated mice or mice that received naïve DCs. These results indicate that HDM induced tolerogenic DCs, which in turn ameliorates DSS colitis. RNAseq showed that HDM upregulated 183 and downregulated 76 genes. These differentially expressed genes may indicate a novel mechanism by which helminths induce a tolerogenic profile in DCs.

Conclusions

HDMs induce tolerogenic DCs and alleviate DSS-induced colitis.

Funding Agencies

NSERC and FRQNT
A13 GUT MICROBIOTA MODULATES CGRP PRODUCTION BY DRG NEURONS IN FEMALE MICE
Authors: Pujo J , De Palma G , Lu J , Collins S M , Bercik P
Published: February 2022

Background

Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Thus, gut microbiota is involved in the regulation of gut nociception but the underlying mechanisms remain poorly understood.

Aims

To investigate the role of gut microbiota in abdominal pain.

Methods

Method: Adult female and male conventionally raised (SPF) or GF mice were used. Their visceral sensitivity was assessed by visceromotor responses to colorectal distension, at baseline (vehicle: Tween 80 10%, Ethanol 10%, saline 80%) and after intracolonic administration of a TRPV1 agonist capsaicin (30 μg), or a mixture of G-protein coupled receptors agonists (GPCR: bradykinin, histamine and serotonin; 30 μg). Neuronal excitability of dorsal root ganglia (DRG) neurons was assessed by calcium imaging using a fluorescent probe Fluo-4 (1 mM) after stimulation with capsaicin (12.5 nM, 125 nM and 1250 nM) or GPCR agonists (0.3 μM, 3 μM and 30 μM). The neuronal production of substance P (SP) and calcitonin gene-related peptide (CGRP) in response to capsaicin (1250 nM) or GPCR agonists (30 μM) was measured by ELISA.

Results

At baseline, GF male mice exhibited higher responses to colorectal distension compared to SPF males, while SPF and GF females displayed similar visceral sensitivity. In contrast, both intracolonic capsaicin and GPCR agonists increased visceral sensitivity in GF females compared to SPF females, while responses were comparable in male groups.

DRG neuronal activation after stimulation with capsaicin or GPCR agonists was similar in SPF and GF mice of both sexes. While stimulated production of SP by DRG neurons was similar in SPF and GF mice, regardless of sex, the production of CGRP in response to GPCR agonists was higher in GF female than SPF female mice.

Conclusions

Our data suggest that visceral sensitivity in vivo differs according to the gut microbiota status, sex and the activation of TRPV1 and GPCR pathways. At the level of DRG neurons, the absence of gut microbiota does not affect the neuronal activation or production of SP. However, GPCR agonists-stimulated release of CGRP is higher in GF female compared to SPF female mice. All together, our data demonstrate that the gut microbiota modulates visceral sensitivity by regulating the production of CGRP in the sensory neurons, especially in female mice. Further mechanistic studies are needed to investigate the role of gut microbiota in visceral sensitivity.

Funding Agencies

CIHR
A30 RECURRENCE RATES AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Djinbachian R , Rotermund C , Taghiakbari M , Enderle M D , Eickhoff A , von Renteln D
Published: February 2022

Background

Complete polyp resection is the main goal of endoscopic removal of large colonic polyps. Resection techniques used for their removal have evolved in recent years and endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) with margin ablation, cold snare polypectomy (CSP), cold snare EMR and underwater EMR have been introduced. Yet, efficacy of these techniques with regard to local recurrence rates (LRR) compared to traditional hot snare polypectomy (HSP) and standard EMR remains unclear.

Aims

We aimed to analyze LRR of large colonic polyps in a systematic review and meta-analysis.

Methods

MEDLINE, EMBASE, EBM Reviews, and CINAHL databases were searched to identify prospective studies reporting LRR or incomplete resection rate (IRR) after colonic polypectomy of polyps >10 mm, published between January 2011 and July 2021. Primary outcome was LRR for polyps >10 mm.

Results

6928 publications were identified, of which 34 prospective studies were included into the analysis. LRR for polyps >10 mm at follow-up (FU) up to 12 months was 11.0% (95% CI 7.1–14.8; 15 studies; 6259 polyps). ESD (1.7%; 95% CI 0–3.4; 3 studies, 221 polyps) and EMR with margin ablation (3.3%; 95% CI 2.2–4.5; 2 studies, 947 polyps) significantly reduced LRR compared to standard EMR without (15.2%; 95% CI 12.5–18.0%; 4 studies, 650 polyps) or with unsystematic margin ablation (16.5%; 95% CI 15.2–17.8; 6 studies, 3183 polyps).

Conclusions

Local polyp recurrence after standard EMR of large colonic polyps is high. LRR is significantly lower after ESD or EMR with routine margin ablation, so that these techniques should be considered standard for endoscopic removal of large colorectal polyps. CSP, cold snare EMR and underwater EMR should only be used within clinical trials until more high-quality data regarding LRR becomes available.

Funding Agencies

None
A43 HIGH MUC2 MUCIN BIOSYNTHESIS BY GOBLET CELLS UNDER METABOLIC STRESS PRODUCE ELEVATED LEVELS OF PRO-INFLAMMATORY CYTOKINES
Authors: Kim A , Moreau F , Gorman H , Chadee K
Published: February 2022

Background

The colonic mucus bilayer is an integral innate host defense mechanism that houses the commensal gut microbiota whilst protecting the underlying mucosa against harmful pathogens. This essential barrier is generated via a highly ER stressful mechanism by goblet cells that produce MUC2 mucin. Goblet cells also produce a variety of proteins and peptides as well as pro-inflammatory cytokines that interact with and activate other arms of the innate immune system. In ulcerative and infectious colitis, goblet cells hyper secrete mucus and become depleted of their mucin stores. However, it is not known if other proteins or pro-inflammatory responses are altered in mucin-depleted goblet cells. Here, we elucidated the molecular mechanisms that regulate pro-inflammatory responses in WT and CRISPR/Cas9 MUC2 KO human goblet cells.

Aims

Hypothesis: MUC2 biosynthesis and production augment pro-inflammatory responses in goblet cells. The specific aims are:

1. To determine the pro-inflammatory responses in WT and MUC2KO goblet cells

2. To determine if the MAPK signaling pathway is altered in WT and MUC2KO goblet cells

Methods

mRNA and protein expression of various pro-inflammatory chemokines/cytokines in WT and CRISPR/Cas9 MUC2KO LS174T goblet cells were analyzed by RT-qPCR and 15-plex Luminex array. IL-22 was used to alleviate ER stress, as quantified by the expression of stress proteins by Western blotting. To determine differences in pro-inflammatory cytokine release, cells were stimulated with phorbol myristate acetate (PMA, positive control), live Entamoeba histolytica (Eh), and lysed soluble amebic proteins (SAP). MAPK signaling was enumerated by specific pharmacological inhibitors and analyzed by Western blotting.

Results

Basally and in response to live Eh, WT goblet cells expressed high levels of the metabolic stress proteins, ATF4, GRP78, and CHOP as compared to MUC2KO cells. In response to PMA, live Eh, and SAP, WT cells expressed high levels of mRNA transcripts and secreted significant amounts of the pro-inflammatory chemokines, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and interleukin-13 (IL-13) as compared to MUC2KO cells. Reducing ER stress with IL-22 significantly augmented IL-8 protein release in both WT and MUC2KO cells. Signaling via the ERK MAPK pathway was elevated in WT whereas in MUC2KO goblet the response was delayed.

Conclusions

This study demonstrates that high MUC2 mucin biosynthesis regulates the expression and secretion of the pro-inflammatory cytokines MCP-1, IL-8, and IL-13. Mechanistically, MUC2 induced metabolic stress regulated MAPK activity for high output pro-inflammatory responses as compared to MUC2KO goblet cells.

Funding Agencies

CIHR
A49 PRECLINICAL STUDIES OF TWO NOVEL LIVE BIOTHERAPEUTIC PRODUCTS FOR THE TREATMENT OF ULCERATIVE COLITIS
Authors: Verdugo Meza A , Ye J , Gill S K , Barnett J A , Haskey N , Gibson D L
Published: February 2022

Background

The therapeutic approaches for ulcerative colitis present a high failure rate. Therefore, more therapeutic options are in the spotlight. Live biotherapeutic products, a more rationalized and tailored approach than probiotics, have a broader effect since they are not limited to a single therapeutic target.

Aims

To characterize the therapeutic effect of BioColoniz and BioPersist, two live biotherapeutic products derived from Lactobacillus reuteri and E. coli Nissle 1917, respectively, in rodent models of colitis.

Methods

To test the therapeutic effect of BioColoniz, 5 weeks old Muc2-/- mice, which spontaneously develop colitis, received a single dose of BioColoniz, L. reuteri or Vehicle via oral gavage; mice were monitored weekly until they showed clinical signs of disease and were euthanized. To evaluate the therapeutic effect of BioPersist, 6 weeks old C57BL/6 mice received BioPersist or vehicle via oral gavage, and then were exposed for 7 days to DSS for induction of acute colitis; parallel, mice received 5-ASA or vehicle daily. For both experiments, colons were collected and evaluated for macroscopic and histopathological changes.

Results

Mice treated with BioColoniz presented lower clinical scores, with a greater weight gain when compared to mice treated with L. retueri or vehicle. The appearance of rectal prolapse, a hallmark of the Muc2-/- model, was only recorded in mice treated with L. reuteri or Vehicle, supporting the protective effect of BioColoniz in the Muc2-/- model. Although the macroscopic analysis showed no changes in colon length among the groups, the histopathological analysis revealed decreased damage in mice treated with BioColoniz, significant when compared to mice who only received the vehicle. In order to evaluate if BioColoniz also protects against the development of comorbid metabolic defects of colitis, mice were also subjected to oral glucose tolerance test, finding that BioColoniz treated mice, especially males, display an improved glucose clearance when compared to L. retueri or vehicle groups. In the DSS model, BioPersist decreased daily clinical scores, significantly delaying the weight loss. The macroscopic analysis showed greater colon length in BioPersist treated mice than in mice treated only with 5-ASA, along with decreased histopathological damage.

Conclusions

Altogether, BioColoniz and BioPersist reduce the colitic phenotype in the Muc2-/- and DSS colitis models, respectively. Furthermore, BioColoniz protects Muc2-/- mice from the metabolic detriments of colitis. Future studies will focus on describing the mechanisms by which BioColoniz and BioPersist confer their therapeutic effect.

Funding Agencies

CCCMSFHR
A61 PRE-ALLOGENIC STEM CELL TRANSPLANT CLINICAL FACTORS AND THEIR ASSOCIATION WITH CHRONIC GRAFT VERSUS HOST DISEASE - A RISK FACTOR ANALYSIS FOR CHRONIC GVHD PREDICTION
Authors: Alajmi A , Al Fedaghi A , Olaiya O
Published: February 2022

Background

Allogeneic stem cell transplant is the only curative treatment for some hematological malignancies but is associated with significant toxicities and morbidities. The main long-term complication that is associated with decreased quality of life is chronic graft versus host disease (cGVHD) which can affect any organ system in the body. When clinicians are faced with the decision of transplanting patients many considerations must be taken into place. Unfortunately, despite counseling patients regarding possible toxicities and morbidities resulting from the allogeneic stem cell transplant including GVHD, we are unable to give accurate risks of cGVHD, especially organ-specific cGVHD, which might otherwise deter patients and clinicians from undertaking the transplant depending on their priorities that determine their quality of life.

Aims

We sought to ascertain which prognostic factors could predict gastrointestinal (GI)/liver specific cGVHD.

Methods

We conducted a retrospective case-control study including a consecutive sample of patients from a single specialty clinic from 2012–2017. Patients with biopsy proven GI/liver cGVHD based on pathology or determined by expert opinion reports were classified as cases and patients who underwent allogenic stem cell transplant without GI symptoms or liver enzyme elevations were controls. Data extracted included: age, gender, chemotherapeutics, donor status (related or unrelated), recipient and donor blood type, stem cell dose (x106 cells), complete blood count and differential, and electrolytes. Logistic regression was used to analyze clinical factors associated with GI/liver specific cGVHD.

Results

Our chart review retrieved 66 patients without GI/liver specific cGVHD and 55 patients that experienced GI/ liver cGVHD. The mean [SD] age of the sample was 50 [14] years and most of the participants in the study were men (59%). The most common cancer was acute myeloid leukemia. Univariate analysis revealed that male gender and stem cell dose were associated with GI/liver cGVHD. After adjusting for potential confounders, history of any acute GVHD demonstrated a statistically significant association with GI/liver cGVHD (adjusted OR [aOR]=2.7; 95% confidence interval=1.0–1.3; p=0.049), while male gender (aOR=2.7; 95% confidence interval=1.2–6.2; p=0.02) and stem cell dose (aOR=1.2; 95% confidence interval=1.0–1.3; p=0.037) remained statistically significant. The combination of these three clinical factors demonstrated fair discrimination (area under the curve=0.69). Other clinical factors were not significantly associated with GI/liver cGVHD.

Conclusions

Male gender, previous episode of acute GVHD, and stem cell dose were strongly associated with gastrointestinal (GI)/ liver cGVHD among patients who receive allogeneic stem cell transplants.

Funding Agencies

None
A63 THE COLONIC PATHOGEN, ENTAMOEBA HISTOLYTICA ACTIVATES CASPASE-4 IN HUMAN MACROPHAGES THAT CLEAVES GASDERMIN D TO FACILITATE IL-1β SECRETION IN THE ABSENCE OF CELL DEATH
Authors: Wang S , Moreau F , Chadee K
Published: February 2022

Background

A hallmark of Entamoeba histolytica ( Eh) invasion in the gut is acute intestinal inflammation dominated by the secretion of pro-inflammatory cytokines. Live Eh in contact with macrophages activates caspase-1 by the recruitment of the NLRP3 inflammasome in a Gal-lectin and Eh cysteine proteases 5 ( EhCP-A5)-dependent manner, resulting in the maturation and secretion of IL-1β. Eh in contact with macrophages also activates caspase-4 by outside-in signaling but it is unclear how Eh-induced caspase-1/4 regulates gasdermin D (GSDMD) cleavage to drive both pore formation and IL-1β secretion without causing cell death. In this study, we interrogated the requirements and mechanism of Eh-induced caspase-4 activation in cleaving GSDMD to mediate bioactive IL-1β release.

Aims

Hypothesis: Eh-induced activation of caspase-4 regulates GSDMD mediated pro-inflammatory responses.

Specific aim: To quantify caspase-1/4 cleavage of GSDMD in Eh-induced pro-inflammatory responses.

Methods

Human PMA-differentiated THP-1 macrophages were used for Eh-macrophage studies. Caspase-1/4 activation and GSDMD cleavage were detected by immunoblot analysis. Bioactive IL-1β secretion was quantified by HEK-BlueTM IL-1β reporter cells via the measurement of secreted embryonic alkaline phosphatase (SEAP) and cell pyroptosis (inflammatory cell death) was determined by LDH assay. Immunoprecipitation was performed in HEK 293T cells transfected with human GSDMD plasmid followed by in vitro caspase cleavage assay.

Results

Unlike caspase-1, Eh-induced caspase-4 activation and IL-1β secretion was independent of the NLRP3 inflammasome as revealed with the use of CRISPR-Cas9 gene edited caspase-1, 4, ASC and NLRP3 macrophages. In the absence of caspase-1, caspase-4 activation was significantly upregulated that promoted the cleavage of GSDMD to induce robust IL-1β secretion. Eh-induced caspase-4 played a major role in triggering IL-1β release and GSDMD pore formation as quantified by SEAP assay and immunoprecipitation of overexpressed GSDMD in HEK 293T cells followed by in vitro caspase cleavage assay. Pharmacological inhibition of GSDMD pore formation and in CRISPR-Cas9 gene edited GSDMD macrophages, Eh-induced IL-1β secretion was highly dependent on GSDMD pore formation and independent of pyroptosis. This was in marked contrast to the positive control, LPS + Nigericin that induced high expression of caspase-1 but not caspase-4 that enhanced GSDMD cleavage and IL-1β secretion and induced massive pyroptosis.

Conclusions

These results suggest that Eh induced a state of “hyperactivated macrophages” that led to caspase-4 dependent GSDMD cleavage and IL-1β secretion in the absence of pyroptosis important in disease pathogenesis.

Funding Agencies

NSERC
A87 CHANGES IN CLINICIAN KNOWLEDGE, COMFORT, PREPAREDNESS, AND ATTITUDES ABOUT ALCOHOL USE DISORDER AND CIRRHOSIS AFTER A BRIEF EDUCATIONAL INTERVENTION
Authors: Johnson E , Ghosh S M , Daniels V J , Tandon P
Published: February 2022

Background

Alcohol use disorder (AUD) is increasing in prevalence and has a substantial impact on morbidity and mortality in people with cirrhosis. The use of screening, brief intervention and referral to treatment (SBIRT) and relapse prevention medications (e.g. acamprosate) are recommended by recent guidelines. Unfortunately, many clinicians report insufficient training to feel confident using these interventions

Aims

We aimed to compare the effect of a brief educational intervention on AUD knowledge, comfort, attitudes, and preparedness in clinicians who provide care to patients with cirrhosis.

Methods

Clinicians were invited to participate in a 1.5-hour educational session conducted by a hepatologist and addiction medicine specialist. The session included information about SBIRT and pharmacotherapy. Pre-training knowledge, comfort, and practice behaviors were assessed using previously published questions. Baseline attitudes were measured using the Short Alcohol and Alcohol Problems Perception Questionnaire. Participants were invited to repeat the questionnaires immediately post-training and statistical analysis conducted.

Results

Eighty-two clinicians attended the session. Among the 38 attendees who completed both the pre- and post-questionnaires, 34% were GIs/internists, 45% were family medicine physicians, and the remainder (21%) did not specify or were not prescribers. Scores for self-reported intention and preparedness to treat AUD, comfort, and knowledge improved significantly from the pre-training phase. Attitudes also improved from the pre-training phase, with significant improvements in the SAAPPQ subscales of role adequacy (p=0.03) and motivation (p=0.04).

Conclusions

Recognizing the small sample size, a brief educational session demonstrated promising results in the promotion of knowledge, attitudes, preparedness, and comfort for clinicians managing AUD in patients with cirrhosis. Feedback from these sessions will be used to design an accredited educational series for roll-out in 2022.

Funding Agencies

Alberta Innovates Health Solutions
A97 DEVELOPMENT OF PREDICTION MODELS FOR THE TRIAGING OF REFERRALS OF INDIVIDUALS WITH SUSPECTED INFLAMMATORY BOWEL DISEASE TO IMPROVE PROMPT ACCESS TO CARE
Authors: St-Pierre J , Frolkis A , Seow C , Oshiomogho J , Bindra G , Heatherington J , Kaplan G G , Panaccione R , Novak K L , Nasser Y , Jijon H
Published: February 2022

Background

The negative impact of a delayed inflammatory bowel disease (IBD) diagnosis has been well established. We created a clinical pathway referred to as the “High-Risk IBD clinic” within a centralized referral program in a tertiary referral centre, in order to improve access to subspecialist care for individuals suspected but not yet diagnosed with IBD. Despite the creation of this specialized clinic, wait times continue to be above the recommended benchmarks established by the Canadian Association of Gastroenterology (CAG).

Aims

The purpose of our study was to create predictive models to identify factors associated with an IBD diagnosis in order to improve triage of referrals of individuals with features highly suggestive of IBD. We hypothesized that features suggestive of IBD could be used to create discriminating prediction models between IBD and IBS.

Methods

We conducted a retrospective cohort study of referrals to the High-Risk IBD clinic from February 2014 to December 2018. Referral information, investigations, endoscopic findings and final diagnosis were obtained from 316 consented individuals. Information required included symptoms (e.g. diarrhea, abdominal pain, rectal bleeding), risk factors (e.g. family history, rheumatological disease) and investigations (e.g. hemoglobin, CRP, abdominal imaging). Univariate logistic regression was performed to explore the association between factors included in the referral form, and a diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC). For creation of predictive models, any variable with a p-value of <0.1 in univariate logistic regression was selected for entry into the multivariate model for CD and UC.

Results

For UC, the predictive model included weight loss, the presence of rectal bleeding and abdominal pain. Using these criteria, the sensitivity and specificity of the model were 62.5% and 74.1%, respectively. The negative predictive value (NPV) was high at 94.2%. For CD, the predictive model included male gender, elevated CRP, presence of anemia and presence of weight loss. The sensitivity and specificity of this model were 61.7% and 71.2%, respectively. As for UC, the NPV was also high (89.2%). For IBS, the most common diagnosis encountered in patients referred to the HR-IBD clinic, the model included absence of weight loss, presence of abdominal pain and female gender. The sensitivity and specificity were 71.6% and 64.0%, respectively. The positive predictive value was 60.6% and NPV was 74.5%.

Conclusions

We established predictive tools associated with a final diagnosis of IBD and IBS as a means to expedite the care of individuals with undiagnosed IBD.

Funding Agencies

CCC
A110 FEASIBILITY OF EUS-GUIDED PORTAL PRESSURE GRADIENT MEASUREMENT WITHOUT DEEP SEDATION: A PATH TO ACCURATE PORTAL PRESSURE DETERMINATION
Authors: Zhao X , Chen Y , Deschenes M , Wong P , Sebastiani G , Chen T , Benmassaoud A
Published: February 2022

Aims

Hepatic venous pressure gradient (HVPG) is the gold standard for the diagnosis and staging of portal hypertension. Previous studies have shown that it underestimates pre-sinusoidal portal hypertension. Endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) can safely measure direct portal vein pressure (PVP) and bridge this diagnostic gap. However, EUS-PPG has so far been performed with patients under deep sedation which can alter HVPG measurement and lead to misclassification of portal hypertension. Ketamine, a conscious sedation agent, has minimal effect on portal hemodynamics. We present our center’s experience with EUS-PPG under ketamine and low dose midazolam.

Methods

We retrospectively reviewed consecutive patients undergoing EUS-PPG with conscious sedation using ketamine and low-dose midazolam (<0.02 mg/kg) at the McGill University Health Centre from February to May 2021. Patients were placed in the left lateral position. Hepatic vein and portal vein were located through EUS via a trans-gastric/hepatic approach. A through the scope 25-gauge needle attached to a manometer was advanced through the liver to measure hepatic vein pressure (HVP) and portal vein pressure (PVP). Three measurements were sampled per vessel and mean pressure differences calculated to obtain PPG. PPG was considered reliable if the differences between the values was no more than 1mmHg.

Results

Three patients underwent EUS-PPG for evaluation of pre-sinusoidal portal hypertension. Cirrhosis was excluded in all patients based on recent liver biopsy or transient elastography. The first patient is a 69-year-old man with splenomegaly and recanalization of the paraumbilical vein on imaging. He received 80 mg of ketamine and no midazolam. HVPG measured was 1 mmHg. EUS-PPG was successful with PPG of 6 mmHg (HVP= 7 mmHg, and PVP= 13 mmHg). The second patient is a 42-year-old woman with previous sleeve gastrectomy and known with portal cavernoma. She received 120 mg of ketamine and 1 mg of midazolam. EUS-PPG was technically difficult due to respiratory movements. The measurement was not considered reliable as differences in PPG were as high as 2mmHg. In this case, PPG was 0mmHg (HVP= 15mmHg, and PVP= 15mmHg). The third patient, a 74-year-old man with hepatic steatosis and splenomegaly received 70 mg of ketamine and 1 mg of midazolam. EUS-PPG was successful (HVP= 3mmHg, PVP= 3mmHg) yielding a PPG 0mmHg. All patients tolerated the procedure well with no procedural or sedation-related complications

Conclusions

Our early experience suggests that EUS-PPG can be successfully and safely performed in patients under conscious sedation with ketamine and low-dose midazolam. This combination may avoid deep sedation with high dose midazolam or propofol which are known to alter accuracy of HVPG.

Measurement of HVP (left) and PVP (right)

Funding Agencies

None
A112 VIDEO CAPSULE ENDOSCOPY REGISTRY OF ONTARIO (VCERO) - RETROSPECTIVE PHASE (NORTHERN ONTARIO REGION)
Authors: Lavalle C , Yaghoobi M , Armstrong D , Tilbe K
Published: February 2022

Aims

The primary aim of this project is to determine the feasibility of establishing and maintaining a registry of all video capsule endoscopy procedures performed at a large regional center. Secondary aims include the determination of indications for capsule endoscopy, quality measures, and procedural outcomes at a large regional center and the comparison of these metrics to other locations globally.

Methods

A retrospective collection and analysis of all video capsule endoscopies performed at Health Sciences North in Sudbury Ontario between 2016 and 2020 has been performed. Information was collected with the aid of a standardized data collection tool and stored under anonymized patient profiles. Once this pilot registry was created, data was pooled for further analysis. Data regarding indications for capsule endoscopy, patient factors, previous investigations, anticoagulant usage, procedure interpretation, need for subsequent interventions, and need for blood transfusion among others was then established for this group. Findings were then compared to previously published regional and global norms where available.

Results

In total 98 video capsule endoscopies encompassing 94 individual patients have been catalogued at the end of the study period. With available information through individual patient records, complete information for all fields of the standardized collection tool was obtained for 91 individual patients. The most common indications for VCE include gastro-intestinal bleeding (38%), anemia (38%), Crohn’s disease (13%) and abdominal pain (3%). In total, 45% of all procedures noted an acute finding in the report. Of VCE performed for gastro-intestinal bleeding, 50% reported on an acute finding while in those performed for anemia, 47% reported on an acute finding. Mortality during the study period was 12% while there was 1 documented incident of capsule retention. The rate of acute findings is greater than previously published international studies.

Conclusions

This project has established the feasibility of the creation of a regional capsule endoscopy registry. Further work to expand the patient pool as well as move to a prospective collection model are reasonable next steps to expand this project. We have also demonstrated significant differences regarding indications for VCE as well as the rate of significant findings of VCE of a our northern cohort compared to previously reported international sites. In particular the high rate of significant findings in anemia warrants further investigations.

Funding Agencies

None
A114 QUALITY AND EFFICACY OF PERCUTANEOUS ENDOSCOPIC GASTROSTOMY: A RETROSPECTIVE CHART REVIEW STUDY
Authors: Aljabri R S , Kwan P
Published: February 2022

Background

Passage of food along the digestive tract can be compromised by a number of conditions. Nasogastric tube (NGT) feeding is used in these cases but prolonged use can lead to various complications. Percutaneous endoscopy gastrostomy (PEG) has been reported as an effective and safe alternative to NGT. Clinical efficacy and adverse events related to PEG insertion are largely dependent on post-procedure care.

Aims

To assess the clinical significance of PEG tube insertion procedure and impact of post-procedure care and diet protocol on associated adverse events and success rate at two Canadian tertiary care units.

Methods

The retrospective electronic chart review was conducted on all patients who underwent endoscopic PEG fixation or replacement procedure at University of British Columbia Gastroenterology clinic and Vancouver General hospital Endoscopy Unit from 1st April 2020 to 31st March 2021. Data related to patient demographics, indications for insertion, insertion technique, quality of PEG insertion protocol, antibiotic prophylaxis, success rate, and rate of PEG-related complications were collected and analysed. An evaluation protocol was devised to evaluate the impact of indication-based diet protocols on frequency of adverse events and success rate. Results are suggested to be analysed using SPSS v 2021 with significance threshold of P-value < 0.05.

Results

43 PEG insertion procedures were performed, of which 3 failed due to structural reasonsincluding post gastric sleeve surgery, small stomach and difficulty in finding transillumination point. 25 cases underwent PEG insertion endoscopically for the first time, and 14 required exchanges, of which 2 underwent non-endoscopic exchange. Of 37 patients who underwent endoscopic PEG insertion 18(48.64%) were males and 19(51.36%) were females. Acute infection was reported in 6(14%) and chronic infection in 4 patients (9.3%). Tube dislodgment was reported in 10(23%), peristomal leak in 4(9.3%), miinor bleeding in 3(6.9%), and post-operative granulation in 4(9%) procedures. The evaluation protocol divides patients into two groups: Group a included d subjects who would receive low-volume (≤150 mL/d) and Group b who would receive a high-volume (≥300 mL/d) of feeding formula.

Conclusions

PEG tube insertion is a very successful procedure with high clinical significance and low complications rate at VGH and UBC. A follow-up plan is therefore being initiated to evaluate impact of feeding volumes on rate of success and adverse events. Combined, the previous studies, suggest that the high-feeding volumes can be safely administered to rapidly attain calorie targets to increase the procedure efficacy. .

Funding Agencies

CAG