OCCURRENCE OF ESCHERICHIA COLI O157 IN GROUND MEATCOMMERCIALIZED IN LEBANESE URBAN CITIES

Escherichia coli O157:H7 (E. coli O157:H7) has been recognized as a major cause of diarrhea and hemolytic- uremic syndrome (HS). The consumption of raw or undercooked meat of bovine origin has been the most common mean of transmitting this organism. No screening of E.coli has been performed in the ground meat commercialized in the Lebanese market. Therefore, the purpose of this study is to evaluate the prevalence of E. coli serotype O157:H7 recovered from ground fresh raw meat collected from different butcheries in Lebanese Urban cities. A total of 73 samples of fresh ground meat was collected from Sin el fil area (n=23), Hadath (n=16), Ghoubayri (n=16) and Antelias (n=18), and investigated for the presence of E. coli O157: H7. E. coli O157:H7 was isolated in 16 (22%) out of 73 meat samples examined. This high prevalence was variable between the different cities, with the highest one in Ghoubayri (43%), followed by Sin el fil (21%), Hadath (12%) and Antelias (11%). This study revealed the presence of E. coli O157:H7 in retail raw meats reaching consumers, especially in crowded urban city such as Ghoubayri. This result is an indication of the poor hygienic level in the different butcheries localized in the Lebanese urban cities, thus reflecting possible risks of infection to people through the consumption of fresh raw/under-cooked meat

Intensification of Solvent Extraction in an Additively Manufactured Microfluidic Separator

Solvent extraction is an integral chemical and biochemical separation process that is drastically intensified in microfluidic systems. A novel high-throughput micro-separator was additively manufactured for the intensification of liquid–liquid separation. The micro-posts array within the flow plate generated a capillary pressure gradient on the non-wetting organic phase, enabling continuous, membrane-free, and density-independent phase separation. The device was integrated with an upstream micromixer for aqueous isobutanol extraction, allowing equilibrium extraction levels within 0.25 s. By capitalizing on the high depth-to-width aspect ratio of binder jetting, hydraulic pressure drops were substantially reduced, avoiding a detrimental effect on separation observed in current micro-separators. This novel architecture also enabled the rare ability to separate both “slug flow” and the highly effective but challenging “dispersed droplet flow”. Near-complete separation of the aqueous and organic phases was attained at flow rates up to 15 ml/min, under interfacial tensions of 48.9 and 10.9 mN/m, and aqueous:organic inlet flow ratios of 1:1 and 2:1. Separation performance deteriorated at 20 ml/min due to an increase of velocity gradients near the outlets, leading the wetting aqueous phase to exit from the organic outlet. Owing to its simplicity, manufacturing merits, and robust separation performance, this device addresses key requirements for achieving industrial-level throughputs using a “scale-up via number-up” approach

Effect of Population Heterogenization on the Reproducibility of Mouse Behavior : A Multi-Laboratory Study

Peer reviewe

Outcome after Surgery for Iatrogenic Acute Type A Aortic Dissection

(1) Background: Acute Stanford type A aortic dissection (TAAD) may complicate the outcome of cardiovascular procedures. Data on the outcome after surgery for iatrogenic acute TAAD is scarce. (2) Methods: The European Registry of Type A Aortic Dissection (ERTAAD) is a multicenter, retrospective study including patients who underwent surgery for acute TAAD at 18 hospitals from eight European countries. The primary outcomes were in-hospital mortality and 5-year mortality. Twenty-seven secondary outcomes were evaluated. (3) Results: Out of 3902 consecutive patients who underwent surgery for acute TAAD, 103 (2.6%) had iatrogenic TAAD. Cardiac surgery (37.8%) and percutaneous coronary intervention (36.9%) were the most frequent causes leading to iatrogenic TAAD, followed by diagnostic coronary angiography (13.6%), transcatheter aortic valve replacement (10.7%) and peripheral endovascular procedure (1.0%). In hospital mortality was 20.5% after cardiac surgery, 31.6% after percutaneous coronary intervention, 42.9% after diagnostic coronary angiography, 45.5% after transcatheter aortic valve replacement and nihil after peripheral endovascular procedure (p = 0.092), with similar 5-year mortality between different subgroups of iatrogenic TAAD (p = 0.710). Among 102 propensity score matched pairs, in-hospital mortality was significantly higher among patients with iatrogenic TAAD (30.4% vs. 15.7%, p = 0.013) compared to those with spontaneous TAAD. This finding was likely related to higher risk of postoperative heart failure (35.3% vs. 10.8%, p < 0.0001) among iatrogenic TAAD patients. Five-year mortality was comparable between patients with iatrogenic and spontaneous TAAD (46.2% vs. 39.4%, p = 0.163). (4) Conclusions: Iatrogenic origin of acute TAAD is quite uncommon but carries a significantly increased risk of in-hospital mortality compared to spontaneous TAAD

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

Funder: American College of Rheumatology Research and Education Foundation; FundRef: http://dx.doi.org/10.13039/100000960Funder: National Institute of Arthritis and Musculoskeletal and Skin Diseases; FundRef: http://dx.doi.org/10.13039/100000069Funder: European League Against Rheumatism; FundRef: http://dx.doi.org/10.13039/501100008741OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups

Outcome after Surgery for Iatrogenic Acute Type A Aortic Dissection

(1) Background: Acute Stanford type A aortic dissection (TAAD) may complicate the outcome of cardiovascular procedures. Data on the outcome after surgery for iatrogenic acute TAAD is scarce. (2) Methods: The European Registry of Type A Aortic Dissection (ERTAAD) is a multicenter, retrospective study including patients who underwent surgery for acute TAAD at 18 hospitals from eight European countries. The primary outcomes were in-hospital mortality and 5-year mortality. Twenty-seven secondary outcomes were evaluated. (3) Results: Out of 3902 consecutive patients who underwent surgery for acute TAAD, 103 (2.6%) had iatrogenic TAAD. Cardiac surgery (37.8%) and percutaneous coronary intervention (36.9%) were the most frequent causes leading to iatrogenic TAAD, followed by diagnostic coronary angiography (13.6%), transcatheter aortic valve replacement (10.7%) and peripheral endovascular procedure (1.0%). In hospital mortality was 20.5% after cardiac surgery, 31.6% after percutaneous coronary intervention, 42.9% after diagnostic coronary angiography, 45.5% after transcatheter aortic valve replacement and nihil after peripheral endovascular procedure (p = 0.092), with similar 5-year mortality between different subgroups of iatrogenic TAAD (p = 0.710). Among 102 propensity score matched pairs, in-hospital mortality was significantly higher among patients with iatrogenic TAAD (30.4% vs. 15.7%, p = 0.013) compared to those with spontaneous TAAD. This finding was likely related to higher risk of postoperative heart failure (35.3% vs. 10.8%, p &lt; 0.0001) among iatrogenic TAAD patients. Five-year mortality was comparable between patients with iatrogenic and spontaneous TAAD (46.2% vs. 39.4%, p = 0.163). (4) Conclusions: Iatrogenic origin of acute TAAD is quite uncommon but carries a significantly increased risk of in-hospital mortality compared to spontaneous TAAD

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia 80% for all items, explaining the higher overall specificity of the criteria set

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Étude de la distribution, des interactions et des capacités régénératrices des cellules souches du muscle squelettique dans l'ischémie critique des membres inférieurs

Notre étude s’est intéressée à l’impact de l’ischémie critique des membres inférieurs (ICMI) chez l’homme sur la densité et les propriétés myogéniques des cellules souches du muscle squelettique - les cellules satellites (MuSCs) - et leur interaction avec les cellules endothéliales (EC). Les MuSCs sont capables de réparer entièrement un muscle via une myo-angiogenèse coordonnée post-lésionnelle mais leur implication dans la physiopathologie de l’ICMI n’a été que peu explorée alors que la trophicité et fonction musculaires conditionnent le sauvetage de membre.Cette étude a été effectuée à partir de muscles gastrocnémiens de patients atteints d’ICMI et de patients témoins où nous avons réalisé 1/ une analyse topographique bi- et tridimensionnelle (3D) de la densité des MuSCs en lien avec la vascularisation, 2/ une analyse fonctionnelle in vitro et in vivo de leur capacité myo-angiogénique et 3/ une analyse transcriptomique en cours d’interprétation sur cellules uniques (single cell RNAseq) avec un intérêt particulier pour les interactions moléculaire entre les MuSCs et les CEs.Nos travaux menés montrent 1/ que les MuSCs sont diminuées en nombre dans les muscles de patients ICMI et que cette perte en MuSCs est associée à une une diminution significative de la densité de capillaires, de la taille des myofibres et du taux de fibres centro-nucléées et à un switch métabolique du typage des fibres musculaires (type I vers type II) 2/ une altération des capacités myogéniques et angiogéniques des MuSC ICMI ex vivo et in vivo, et 3/ une signature myo-angiogénique propre des MuSCs ICMI évaluée par single cell RNAseq.Ce travail original permet d’ouvrir une nouvelle voie dans la compréhension des conséquences de l’ICMI sur la perte de fonction régénérative des cellules souches du muscle, dont la compensation après identification de potentielles cibles constituerait une piste thérapeutique sérieuse.Our study objective was to evaluate the impact of chronic limb-threatening ischemia (CLTI) in human, on the distribution and myogenic capacities of skeletal muscle stem cells -I.e, satellite cells (MuSC) - and their interaction with endothelial cells (EC). MuSC allow muscle regeneration after injury, through a coordinated mho-angiogenesis, but their implication in CLTI pathophysiology remain unexplored, while muscle trophicity and function are essential to limb salvage.This study required the collection of gastrocnemius medialis samples obtained intra-operatively in CLTI and control patients and explored by 1/ A topographic bi and tridimensional (3D) analysis of the SC density, in relation to neighboring capillaries 2/ An in-vitro and in-vivo functional analysis addressing SC myogenic and angiogenic potential and 3/ an on-going transcriptomic analysis using single-cell RNA Seq, with particular focus on molecular interaction between MuSC and EC.Our results show 1/ a significantly diminished amount of MuSC in CLTI samples, associated with a significant decrease of capillaries density, myofibers area, and Centro-nucleated myofibers rate, and a metabolic switch from Type I to type II fibers. 2/ an alteration of both myogenic and angiogenic capacities of CLTI MuSC in-vitro and in-vivo and 3/ a myo-angiogenic signature specific to MuSC evaluated by SC-RNAseq.This original work helps understand the consequences of CLTI on the loss of regenerative potential of muscle stem cells, that would be improved by identifying and promoting/inhibiting potential target pathways