bluuebunny/crossref_metadata_2025_split huggingface dataset:
A224 COVID-19 INFECTION IN LIVER TRANSPLANT RECIPIENTS: CLINICAL FEATURES, HOSPITALIZATION, AND MORTALITY FROM A CANADIAN MULTICENTRE COHORT
Authors: Smith M K , Chow J , Huang R , Omar M , Ebadi M , Wong P , Huard G , Yoshida E M , Peretz D , Brahmania M , Montano-Loza A J , Bhanji R 
Published: February 2022

Abstract

Background
The COVID-19 pandemic has brought significant challenges to clinicians caring for liver transplant (LT) recipients. Researchers have sought to better understand the risk and clinical outcomes of LT recipients infected with COVID-19 globally, however, there is a paucity of data from within Canada.

Aims
Our multi-center study aims to examine the characteristics and clinical outcomes of LT patients with COVID-19 in Canada.

Methods
We identified a retrospective cohort of adult LT recipients with RT-PCR confirmed COVID-19 from 7 Canadian tertiary care centers between March 2020 and June 2021. Demographic and clinical data were compiled by clinicians within those centers. We identified liver enzyme profile at the time of COVID-19 infection, immunosuppression type and post-infection adjustments, rate of hospitalization, ICU admission, mechanical ventilation, and death.

Results
A total of 49 patients with a history of LT and COVID-19 infection were identified. Twenty nine patients (59%) were male, the median time from LT was 66 months (1, 128) and the median age at COVID-19 infection was 59 years (52, 65). At COVID-19 diagnosis, the median ALT was 37 U/L (21, 41), AST U/L was 34 (20, 37), ALP U/L was 156 (88, 156), Total Bilirubin was 11 umol/L (7, 14), and INR was 1.1 (1.0, 1.1). The majority of patients (92%) were on tacrolimus monotherapy or a combination of tacrolimus and mycophenolate mofetil (MMF); median tacrolimus level at COVID-19 diagnosis was 5.3 ug/L (4.0, 8.1). Immunosuppression was modified in 8 (16%) patients post-infection; either the tacrolimus dose was reduced or MMF was held. One patient developed acute cellular rejection which recovered after re-initiation of the prior regimen. Eighteen patients (37%) required hospitalization, 6 (12%) were treated with dexamethasone, and 3 (6%) required ICU admission and mechanical ventilation. Four patients (8%) died due to complications of COVID-19. On univariate analysis, neither age, sex, co-morbidities nor duration post-transplant were associated with risk of hospitalization.

Conclusions
In our national retrospective study, approximately 40% of patients required hospitalization with a mortality rate of &lt; 10%. Previous studies have shown proximity to LT as an independent factor for mortality with COVID-19; the median time from LT for our patients was 5 years, which may explain the lower mortality rate. Of note, the median tacrolimus levels were much lower in comparison to the target of 8–10 ug/L used in the first year post-transplant. As the landscape of COVID-19 changes with vaccination, evolving treatments, and increasing rates of variant transmission, additional studies are required to continue identifying trends in clinical outcomes.

Funding Agencies
None
A227 THE EFFECTIVENESS OF PEG 3350 COMPARED TO LACTULOSE FOR THE TREATMENT OF ACUTE HEPATIC ENCEPHALOPATHY IN ADULT CIRRHOTIC PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Afzaal T , Karvellas C J , Dionne J 
Published: February 2022

Abstract

Background
Cirrhosis is the leading cause of liver-related death globally. Hepatic encephalopathy (HE) leads to significant morbidity and mortality. Lactulose is the current gold standard treatment for HE; it eliminates nitrogenous waste from the gut. Polyethylene glycol 3350–electrolyte solution (PEG) is a safe, common and effective purgative with recent studies suggesting its efficacy resulting in faster resolution of HE and shorter hospital length of stay.

Aims
To assess the efficacy and safety of PEG 3350 compared to lactulose in adult cirrhotic patients 18 years of age and older with overt hepatic encephalopathy on patient important outcomes including: improvement of hepatic encephalopathy, hospital length of stay and mortality.

Methods
We reviewed databases MEDLINE, EMBASE, OVID, CINAHL, Cochrane Database, PubMed, Trip database, the grey literature, and clinicaltrials.gov from inception to December 2020: PROSPERO CRD42021257641. Search strategy was developed in conjunction with medical librarian. Randomized controlled trials (RCTs), either published or non-published, were included in the review. Continuous data was analyzed using mean difference with random-effects model. Dichotomous data was analyzed using the Mantel-Haenszel method using random-effects model. Statistical effect-size heterogeneity was assessed using Chi2 test and quantifying the relative proportion of variation using I2 statistic. The overall certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations system (GRADE).

Results
From the 68 studies, 16 were assessed for full text review from which 5 studies were included in the meta-analysis representing a total of 351 patients. The primary outcome of mean change in Hepatic Encephalopathy Scoring Algorithm (HESA) at 24-hours from baseline demonstrated an improvement in the PEG group compared to lactulose group [Mean difference (MD)= 0.60, 95% CI (0.20, 1.01)]. In comparison to lactulose, PEG also demonstrated a shorter hospital length of stay [MD = -1.00, 95% CI (-1.99, -0.01)], shorter time to HE resolution [MD= -1.49, 95% CI (-1.81, -1.16)] and showed a mortality benefit [RR=0.35, 95% CI (0.13 to 0.92)]. There was no significant difference between change in ammonia levels at 24 hours [MD= -25.80, 95% CI (-95.39, 43.78)].

Conclusions
PEG leads to a faster improvement and resolution of HE when compared to the current standard of care, lactulose.

Funding Agencies
None
A229 GUT MICROBIOTA PROFILES, DIET AND SHORT-CHAIN FATTY ACIDS AS PREDICTORS OF GENERALIZED ANXIETY DISORDER
Authors: Rabbia V , De Palma G , Lu J , Verdu E , Armstrong H , Collins S M , Anglin R , Surette M , Bercik P 
Published: February 2022

Abstract

Background
Generalized anxiety disorder (GAD) is a debilitating chronic condition with a lifetime prevalence of 4–7% worldwide. Both diet and gut microbiota have been previously associated with anxiety.

Aims
To investigate whether bacterial taxa and/or nutrients associate with GAD, and whether they differ from those of healthy controls (HC).

Methods
Patients with GAD (n=82) and matched HC (n=97) were assessed by validated questionnaires for anxiety (DASS-21), gastrointestinal (GI) symptoms (Rome III, Short-Form Leeds Dyspepsia), and dietary profiles by the Dietary Questionnaire for Epidemiological Studies. We quantified several blood and stool biomarkers, including inflammatory and neuroactive metabolites, as well as short-chain fatty acids. Stool microbiota profiles were assessed by16S rRNA gene sequencing through Illumina. The data was then analyzed following the pipelines of dada2 and by multiple factor analysis (MFA), mean comparisons, correlation, LEfSe and XGBoost using R software (v.1.2.1335). Multiple comparison results were corrected allowing 5% of FDR.

Results
Using MFA to analyze all variables, we identified 3 clusters: one mainly composed of HC (n=99, 91% HC, GI symptoms in 25% of subjects), a second mixed cluster (n=30, 80% GAD, GI symptoms in 80%) and a third cluster mainly composed of GAD patients (n=50, 98% GAD, GI symptoms in 86%). When focusing only on the HCs of cluster 1 (n=90) and GADs of cluster 3 (n=49), we found higher GI symptoms, body mass index, serum C-reactive protein and stool calprotectin levels (adj. p=1.3x10-9, 0.001, 0.017 and 0.017, respectively) and lower concentrations of propionate, butyrate and acetate in GAD compared to HC. GADs also reported overall lower caloric intake (kJ/day; adj. p=1.7x10-4) in the food frequency questionnaire. Fibre (g/day) was the macronutrient most negatively associated with anxiety scores (R=-0.44; adj. p=4.2x10-5). Bacteroides was the only bacterial taxon significantly associated with GAD, as well as with anxiety scores (R=0.31, adj. p=0.003). Interestingly, Bacteroides/fiber ratio was strongly correlated to anxiety scores (R=0.58, adj. p=2.7x10-09). Furthermore, demographic, biomarkers and bacterial taxa data were predictive of the patients’ disease state with 92.8% accuracy. The features that aid the model to predict disease state were Bacteroides/fiber ratio, GI symptoms and stool acetate levels.

Conclusions
Our results suggest that most GAD patients differ in dietary and microbiota profiles from HCs, and that the Bacteroides/fiber ratio, stool acetate and GI symptoms might be good predictors of disease state. Furthermore, these data strongly support the role of microbiota-gut-brain axis in genesis of psychiatric diseases, and they will inform mechanistic studies in gnotobiotic mouse models.

Funding Agencies
NIH
A237 VIRULENCE POTENTIAL OF BACTERIA ISOLATED FROM NON-INFLAMED COLON IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES
Authors: Arjomand Fard N , Bording-Jorgensen M , Webb J , Veniamin S , Perry T , Wine E 
Published: February 2022

Abstract

Background
As inflammation can impact microbes, our lab has focused on non-inflamed bowel sections of patients with inflammatory bowel diseases (IBD) and found bacterial alterations in the terminal ileum. We are also interested in the appendix given the involvement of the peri-appendicular region and effects of appendectomy in ulcerative colitis.

Aims
In this study, we aimed to identify and evaluate microbes from the appendix and non-inflamed regions of the colon in IBD patients. We hypothesized that microbes originating from the non-inflamed sections of the colon or appendix are more invasive and could trigger inflammation in IBD patients.

Methods
16S DNA Sanger sequencing was performed on bacteria, aerobically and anaerobically cultured from tissues of the appendix, peri-appendicular region, cecum, and ascending colon, collected from the resected colons of 5 pediatric IBD patients. The invasive capacity of the identified bacteria was evaluated by gentamicin protection assays on Caco-2 intestinal epithelial cells in vitro. Presence of select invasive or adhesive genes in the bacteria was assessed by PCR.

Results
Escherichia coli was the most frequently cultured species in the aerobic cultures; additional aerobic species included Enterococcus and Klebsiella. Bifidobacterium and Erysipelatoclostridium were identified among the anaerobic cultures. Gentamicin protection assays indicated that Klebsiella isolated from the peri-appendicular region was significantly more invasive (mean ~3000 CFU/ml) than HB101 (~1000 CFU/ml; non-invasive control; P&lt;0.05). Enterococcus avium and Enterococcus faecalis were also more invasive than HB101 in the peri-appendicular region (~10000 CFU/ml) and cecum (~4000 CFU/ml; P&lt;0.05), respectively. E. coli isolated from the appendix showed a higher invasive potential (~3000 CFU/ml) than E. coli isolated from other sections. Additionally, PCR showed that E. coli obtained from different sections, except the ascending colon of one the patients, had the fimH gene while the other types of bacteria did not. None of the isolated bacteria had Hemolysin ( hlyA) or attaching and effacing ( eaeA) genes.

Conclusions
Bacteria, especially E. coli, from non-inflamed bowel in IBD (including the appendix) appear to have increased invasive potential. This suggests that the microenvironment in these regions could be altered, resulting in increased invasion of bacteria or the gut harboring more invasive microbial populations in IBD patients. As a result, inflammation could be triggered or exacerbated through this reservoir of pathobionts.

Funding Agencies
CIHR
A240 OPIOID-INDUCED HYPEREXCITABILITY IN DRG NEURONS IS MEDIATED BY DOR-DEPENDENT ENDOCYTOSIS
Authors: Jaramillo Polanco J , Lopez Lopez C , Lomax A E , Reed D E , Vanner S 
Published: February 2022

Abstract

Background
Opioids are effective for the treatment of abdominal pain but are also associated with tolerance, and increased dosing leads to severe side effects. We previously showed that prolonged exposure to high doses of opioids evoked paradoxical hyperexcitability of colonic afferent nerves that was mediated by δ-opioid receptor (DOR) signaling. Recent studies suggest that DOR-dependent analgesia is mediated not only by G proteins but also via receptor endocytosis and downstream signaling, but it is unclear what intracellular signaling mechanisms are underlying opioid-induced hyperexcitability.

Aims
To examine the mechanisms underlying DOR-mediated hyperexcitability of dorsal root ganglia (DRG) neurons.

Methods
We assessed the excitability of DRG neurons isolated from C57BL/6 mice by measuring the rheobase (minimal current to elicit an action potential, i.e. lower rheobase=increased excitability) using perforated patch-clamp recordings. Dissociated neurons were exposed to a high concentration (10 µM) of the μ-opioid receptor agonist DAMGO, the DOR agonist DADLE, or the weakly internalizing DOR agonist ARM390 overnight. To examine the role of receptor endocytosis and intracellular receptor activation underlying the excitatory effect by opioids, DRG neurons exposed to DAMGO or DADLE were preincubated with the membrane-permeable opioid receptor antagonist naloxone or the endocytosis inhibitor Pitstop2. To further understand the mechanisms involved in the hyperexcitability evoked by opioid re-exposure, following overnight incubation with high concentrations of DAMGO or DADLE, neurons were washed for 1 hr and treated either with the PKA inhibitor H89 or the PKC inhibitor GFX before re-exposure to DAMGO or DADLE at a low concentration (10 nM).

Results
Neurons exposed to 10 µM DAMGO or DADLE were hyperexcitable (rheobase decreased 25 % and 26 % compared to controls respectively; p≤0.05, 2-way ANOVA). Naloxone and Pitstop2 blocked the increased excitability of DRG neurons induced by overnight incubations with either DAMGO or DADLE. In contrast to the hyperexcitability induced by DAMGO and DADLE, overnight incubation with 10 µM ARM390 decreased excitability (rheobase increased 31%, p≤0.05, unpaired t-test). The hyperexcitability induced by DAMGO and DADLE was reversed after a 1 hr washout but acute reapplication of a low concentration of DAMGO or DADLE (10nM) now evoked hyperexcitability (rheobase decreased 34 and 35 % respectively, p≤0.05, 2-way ANOVA). This effect was prevented by inhibiting PKC but not PKA.

Conclusions
Our data suggest that the DOR-dependent hyperexcitability evoked by prolonged exposure to high concentrations of opioids is dependent on receptor endocytosis and downstream PKC signaling. Targeting these pathways could mitigate the hyperexcitability of pain signaling neurons caused by high doses of opioids.

Funding Agencies
CCC
A252 DO GLIM CRITERIA FOR DIAGNOSING MALNUTRITION AGREE WITH SGA IN HOSPITALIZED PATIENTS RECEIVING TPN?
Authors: Vantomme E , Sulymka B , Stevens M , Duerksen D 
Published: February 2022

Abstract

Background
The Global Leadership Initiative on Malnutrition (GLIM) proposed a new two-step model for diagnosing malnutrition in 2019. A combination of two etiologic and three phenotypic criteria are used to assess malnutrition. The Subjective Global Assessment (SGA) is the most well validated assessment tool for diagnosing malnutrition in hospitalized patients. Evaluation of the performance of GLIM criteria in comparison to SGA is necessary before implementing this new diagnostic tool in practice.

Aims
To compare GLIM criteria to SGA in assessing malnutrition severity in hospitalized patients requiring parenteral nutrition (PN).

Methods
This is a retrospective analysis of a prospectively collected database of malnourished hospitalized adult patients requiring PN admitted between March 2020 and March 2021 to an academic hospital in Winnipeg, Canada. 172 cases were evaluated. GLIM malnutrition screening was considered positive if one etiologic (high CRP or low food intake) and one phenotypic (weight loss or low BMI) criteria were identified. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated and expressed with a Wilson 95% confidence interval.

Results
The prevalence of malnutrition using SGA B or C criteria was 82.3% (CI 73.8, 85.5). Using GLIM criteria, the prevalence of malnutrition was 33.7% (27.1, 41.1). The prevalence of severe malnutrition using SGA C was 32.6% (26.0, 40.0) and using GLIM criteria the prevalence was 19.2% (14.0, 25.7). Using any combination of GLIM criteria versus SGA B or C combined, the PPV was 100% (90.4, 100) and the specificity was 100% (89.9, 100); NPV was 30.0% (22.0, 38.5) and the sensitivity was 42.0% (34.1, 50.4). Using any combination of GLIM criteria versus only SGA C patients, PPV decreased to 72.4% (59.8, 82.3) and specificity was 86.2% (78.8, 91.3); NPV increased to 87.7% (80.4, 92.5) and sensitivity was 75.0% (62.3, 84.5). Comparing severely malnourished patients by GLIM criteria to only SGA C patients, PPV was 97% (84.7, 99.5) and specificity was 99.1% (95.3, 100). NPV was 82.7% (75.6, 88.1) and sensitivity was 57.1% (44.1, 69.2).

Conclusions
Using SGA as the gold standard for diagnosing malnutrition in hospitalized patients requiring PN, GLIM criteria had a very high PPV but unacceptably low NPV in diagnosing malnutrition. The NPV improved when GLIM criteria was compared only to severely malnourished patients by SGA. Importantly, in comparing severely malnourished patients by GLIM and SGA criteria, the sensitivity was also unacceptably low. Based on these results, GLIM criteria are most useful in confirming the diagnosis of malnutrition or severe malnutrition; a negative result should not reassure clinicians that severe malnutrition is absent. Further studies evaluating GLIM criteria are needed before it replaces SGA as a decision making tool.

Funding Agencies
None
A260 ACUTE PANCREATITIS IN JORDANIAN CHILDREN
Authors: Altamimi E M , Droubi B 
Published: February 2022

Abstract

Background
Acute pancreatitis is a uncommon disease in children. The difference between pediatric and adult pancreatitis limit the ability of extrapolating the adults data and magnify the need for further pediatric research.

Aims
We aimed to describe the demographics, clinical presentation and findings of acute pancreatitis in Jordanian children. In addition, we discuss the diagnostic criteria of AP and compare the role of various labratory and radiological investigations in the diagnostic process in our cohort.

Methods
This is a retrospective study involving children below 18 years of age, diagnosed with acute pancreatitis at King Abdullah University Hospital, a tertiary healthcare center in Irbid, Jordan.
Patient electronic records from 2011 to 2020 were manually reviewed and data collected into an excel sheet. The data included their demographics (Age, sex, age at first recurrence in case of recurrent pancreatitis) and clinical data (presentation, physical findings, laboratory and radiological investigations, interventions and outcomes). Those with insufficient data were excluded.

Results
A total of 22 patients with 59 episodes of AP were identified. Of those patients, 11 (50%) were males, and 11 (50%) had only a single AP episode. The mean age during the first attack of AP was 10 years (SD = 3.6 y, N = 21) and the youngest was 3.45 years.
Of the 22 patients who had the first AP episode, 11 (50%) had at least one more episode of AP later on. In those who did have recurrence; The median duration between the first and second episodes was 2.7 months, IQR = 11 mo. The median length of hospital stay was 3 days, IQR = 4 days.
Abdominal pain was the most common presenting symptom of AP (96%). Nausea and vomiting were less common (67% and 50%, respectively).
The cause of pancreatitis was identified in 18 (82%) children, while 4 (18%) were labelled as idiopathic. The most common known cause in our cohort was congenital biliary-pancreatic abnormalities; namely choledochal cyst and pancreatic divisum (6, 27%) followed by genetic cause (4, 18%) and biliary pancreatitis (4,18%).
Abdominal ultrasound (US) was the most used diagnostic imaging (33 exams). The most common finding was bulky and enlarged pancreas in 9 exams. MRCP evaluation was available for 10 episodes; 3 exams showed a normal pancreas, while 2 confirmed the suspicion of pancreatic divisum, 1 suggested cholangitis. 1 visualized a small choledochal cyst that was undetected with neither US nor CT.
Development of peripancreatic fluid collection (pseudocyst) was seen in 4 patients, two of which underwent intervention, one was treated with endoscopic gastro-cystic drainage and the other was treated with surgical drainage. Of the 22 children and 59 AP episodes, only 1 died.

Conclusions
Acute pancreatitis is uncommon in Jordanian children. Although the small number in our cohort, we reported different etiological spectrum compared to reported literture.

Funding Agencies
None
Could Europe Apply a Suitable Control Method for the Small Hive Beetle (Coleoptera: Nitidulidae)?
Authors: Sabella Giorgio , Mulè Rosaria , Robba Lavinia , Agrò Alfonso , Manachini Barbara 
Published: February 2022

Abstract
The European bee, Apis mellifera L. (Hymenoptera: Apidae), is a fundamental resource for the pollination of a great variety of botanical species used by humans for sustenance. Over the last few decades, bee colonies have become vulnerable to a new pest that has advanced beyond its native sub-Saharan territory: the small hive beetle, Aethina tumida Murray (Coleoptera: Nitidulidae). This currently presents a pressing problem in the United States and Australia, but it has also been recorded in Portugal and Italy and it is likely to spread in the rest of Europe too. This study represents a systematic review, based on EFSA guidelines, of the various control treatments for small hive beetles in order to identify the most effective methods as well as, those with no effects on bee colonies. The results show that the bulk of these studies were performed in the United States and that a number of treatments are suitable for the control of A. tumida, though some have negative effects on bees while others have low effectiveness or are ineffective. The best results are those with the entomopathogenic nematodes of the genus Steinernema and Heterorhabditis, but also with formic acid or diatomaceous earth. Various products containing insecticides have been effective, for example, Perizin (Bayer), GardStar (Y-Tex), CheckMite+ strips (Bayer), but Apithor (Apithor ) cannot be used in Europe because it contains Fipronil, which has been banned since 2013. Some common products like bleach and detergent have also been effective.
International Criminal Liability for Spreading Disinformation in the Context of Mass Atrocity
Authors: Holvoet Mathias 
Published: February 2022

Abstract
In the context of international crimes, falsehoods — ranging from selective reporting of facts, deliberate mischaracterization of events and adversaries, or even plain fabrication and lies — constitute a breeding ground in which incitement to commit violence can thrive. While disseminating such falsehoods does not constitute a direct call to commit physical violence, it nevertheless sows the seeds for mass atrocities. This article considers the outer limits of International Criminal Law (ICL) — defined by the principle of culpability — by enquiring whether campaigns of disinformation in the context of mass atrocities could ever give rise to individual responsibility. On the basis of the Fritzsche, Gvero and Mbarushimana cases, liability for disseminating disinformation might in principle be engaged before, during and even after the commission of such crimes. Recent concerns about the role of Facebook in Myanmar also pose the question whether social media companies or their personnel may be liable for amplifying disinformation campaigns. Yet, overall, these cases show the unease of ICL in criminalizing disinformation contributing to atrocity crimes.