Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773)

BACKGROUND AND AIM: High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. METHODS: The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. SUMMARY: The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping

Place of magnesium sulfate in cardiopulmonary resuscitation. A systematic review and meta-analysis

INTRODUCTION: Sudden cardiac arrest treatment is challenging, And the effectiveness of resuscitation procedures — especially in pre-hospital conditions — is low. The purpose of this meta-analysis is to investigate the effects of magnesium sulfate (MgSO4) in cardiac arrest on the return of spontaneous circulation (ROSC) and survival to hospital discharge. MATERIAL AND METHODS: We searched in MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov, Web of Science up to May 25, 2020, and we conducted a systematic review and meta-analysis. We synthesized results by using mean differences, and odds ratios. The overall incidence and outcome of cardiac arrest were assessed using a random-effects meta-analysis. RESULTS: A total of 5 eligible studies were included in this meta-analysis. Survival to discharge was higher in magnesium sulfate group compared to placebo group (9,5% vs. 8.2% respectively; OR = 1.17; 95% CI: 0.61, 2.23; p = 0.64). Higher survival rate to hospital admission was observed in the placebo group — 26.9% compared to the group where magnesium was administered — 25.7% (OR = 0.93; 95% CI: 0.59, 1.47; p = 0.77. CONCLUSIONS: In conclusion, this meta-analysis indicates no statistically significant benefit of resuscitation with magnesium sulfate compared to the placebo. Thus, due to the low number of studies we recommend future randomized controlled trials to identify which anti-arrhythmic drug we should use on shock-refractory cardiac arrest. Copyright © 2020 Via MedicaEuropean Research Council, ERCAcknowledgments: Study supported by the ERC Research NET and Polish Society of Disaster Medicine

Supplementary Material for: Influence of Exclusive Enteral Nutrition Therapy on Bone Density and Geometry in Newly Diagnosed Pediatric Crohn's Disease Patients

<b><i>Background and Aims:</i></b> Exclusive enteral nutrition (EEN) induces remission in patients with Crohn's disease (CD). We investigated the short-term impact of EEN on bone quality and muscle mass in children with CD. <b><i>Methods:</i></b> Ten newly diagnosed CD patients (7 male, 10.6-17.7 years of age) were assessed by peripheral quantitative computed tomography (pQCT) at the forearm before starting an 8-weeks treatment with EEN, and after 12 and 52 weeks. No steroids or biologicals were applied. Trabecular and cortical bone mineral density, total bone, and muscle cross-sectional area (CSA) were measured by pQCT and expressed as age- and sex-specific z-scores; size-dependent CSAs were corrected for low height for age. Wilcoxon rank sum test was applied. <b><i>Results:</i></b> Remission at week 12 was achieved in 8 patients; 2 still had mild disease. Initially low trabecular density z-scores improved (+0.3; p = 0.006) at week 12; simultaneously, the increased cortical density z-scores normalized (-0.4; p = 0.027). The low z-score for muscle CSA corrected for height (median -2.5, range -3.49 to -0.97) increased within 12 weeks (+1.0; p = 0.002) with no further improvement thereafter. <b><i>Conclusions:</i></b> The results indicate disturbed bone remodeling and severely impaired muscle mass in newly diagnosed CD children. Bone metabolism and muscle mass improved within 3 months after starting EEN with no further normalization thereafter

Impact of chronic obstructive pulmonary disease and dyspnoea on clinical outcomes in ticagrelor treated patients undergoing percutaneous coronary intervention in the randomized GLOBAL LEADERS trial

Contains fulltext : 225457.pdf (Publisher’s version ) (Closed access)AIMS: To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. METHODS AND RESULTS: This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21-3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58-1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm. CONCLUSION: In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER: NCT01813435

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: An updated review

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19. © 2020 The Author(s)

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice

Background &amp; Aims The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. Methods We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. Results Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61–99.99); the PPV was 100.00 (95% CI, 98.68–100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67–99.96) to 100.00 (95% CI, 99.23–100.00). Conclusions Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555. © 2017 AGA Institut