bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract

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

Abstract

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 &gt;10 mm, published between January 2011 and July 2021. Primary outcome was LRR for polyps &gt;10 mm.

Results
6928 publications were identified, of which 34 prospective studies were included into the analysis. LRR for polyps &gt;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

Abstract

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

Abstract

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

Abstract

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