Search

Objectives Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies showed a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. Methods This prospective, multicentre cohort study titled “AutoPilot-Dx”, aimed to validate signature performance and estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. Results In total, 1140 patients were recruited (2/2017–12/2018), of which 1008 met eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with sensitivity of 93.7% (95% CI, 88.7–98.7), specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), negative predictive value of 98.9% (98.0–99.8), and 9.8% equivocal test results. The signature performed consistently across different patient subgroups and detected bacterial immune response in viral PCR positive patients. Conclusions The findings validate high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort and support its potential to reduce antibiotic overuse in children with viral infections. Trial registration Clinicaltrials.gov identifier: NCT03052088.

Supplemental Digital Content is available in the text., Objectives: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. Design: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. Setting: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. Patients: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. Interventions: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. Measurements and Main Results: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3–131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0–5 and 0–14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). Conclusions: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

Introduction: Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT) while full engraftment remains a challenge in some recipients. Therapeutic approaches, such as recombinant hematopoietic growth factors, salvage only a minority of patients leaving affected patients at risk for recurrent infections and multiple blood products transfusions. PLX-R18 cells have been shown to mitigate bone marrow failure in rodent and non-human primate models. Further, these human placenta-derived mesenchymal-like adherent stromal cells secrete many cytokines after intramuscular (IM) injection that have been shown to stimulate growth and migration of bone marrow cells in vitro, e.g. MCP-1, IL-6, and IL-8. The initial results of the first cohort of this phase I trial were previously reported (ASH 2018 abstract 3379). Methods: Enrollment for this multi-center, open label, dose-escalation, phase I trial (ClinicalTrials.gov: NCT03002519) began in October 2017. Eligibility criteria included patients age ≥18 years who underwent either autologous (auto) or allogeneic (allo) HCT but suffered from incomplete hematopoietic recovery at least 3 months post-transplant, defined as failure to maintain either hemoglobin (Hb) >8g/dL and/or neutrophil count (ANC) >1,000/μL and/or platelet (PLT) count >50,000/μL. Other eligibility criteria included no evidence of underlying malignancy at time of enrollment, no active infection and no evidence of grade 3-4 acute or severe chronic GvHD. Subjects were enrolled into 3 dose-escalating cohorts: low-dose at 1M cells/kg (n=3), intermediate-dose at 2M cells/kg (n=6), and high-dose at 4M cells/kg (n=10). The specified dose of PLX-R18 cells was injected IM in multiple locations and given twice, 1 week apart. Cohorts were recruited sequentially, and progression to the next cohort was based on the safety assessment of its predecessor. Adverse event grading used the NCI CTCAE criteria. As of July 2020, all patients in cohorts 1 and 2 (3 & 6 patients, respectively) and 10 patients in cohort 3 were treated. Data were analyzed using the lmerTest package (ver. 3.1.0) in R (ver. 3.6.1) to produce baseline-adjusted least square means. As study is in progress and data collection ongoing, not all subjects have data on all parameters for all time points. Results: Data on 19 subjects (29-75 yrs) with either allo (n=17) or auto (n=2) HCT are reported herein. Not all patients reached the 9 month time point. Four patients died while on study and 2 withdrew consent within the 1 year follow up period. All deaths and other severe adverse events (SAEs) occurred due to progression of primary disease and were assessed as not related by investigators and sponsor. Most frequent related AEs were injection-site reactions. The table summarizes number of patients who improved from below the critical level, as defined above, at day 0 to above the critical level for a sustained period. Only those patients that were below the critical blood levels at day 0 are shown. To date, the majority of such patients improved to above the critical level after treatment. For example, 9 patients had ANC The plots show changes in Hb, ANC and PLT up to 9 months following treatment. The dashed lines represent respective critical levels. Overall, there was improvement in the 3 parameters, with the greatest improvement observed in patients receiving the predicted optimal dose of 4M cells/kg. In this cohort, Hb levels increased from 9.29±0.5 to 13.19±1.2 (p=0.0019), ANC increased from 1.09±0.6 to 5.13±1.7 (p=0.018) and PLT increased from 45.7±10 to 175.9±28 (p=0.000012). Conclusions: Treatment with PLX-R18 is safe, well-tolerated and clearly effective in some patients. The most frequent AEs were reversible injection site reactions, all without sequelae. An overall improvement was observed in most patients, and among the high-dose cohort clinically impressive improvements in Hb, ANC and PLT were observed. The trial continues to follow up on patients. Upon completion, a large phase II trial, using the optimal dose, is considered for the same indication. Other attractive clinical areas for PLX-R18 therapy include acute radiation syndrome, bone marrow failure, aplastic anemia, myelofibrosis and with HCT as a "pan" cytokine to enhance rapid count recovery in all cells lines. Figure Disclosures Lazarus: Pluristem ltd: Consultancy. McGuirk:Astellas: Research Funding; Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Rowley:AbbVie: Current equity holder in publicly-traded company; FATE Therapeutics: Consultancy. Ofir:Pluristem: Current Employment. Shani:Pluristem ltd: Current Employment. Rowe:Pluristem ltd: Consultancy.

Background Identifying bacterial coinfection in influenza patients can be difficult as the symptoms of simple influenza versus mixed infections are often similar, leading to antibiotic overuse. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind validation studies. Here we sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection. Material/Methods The study population included 653 febrile pediatric and adult patients prospectively recruited in the ‘Curiosity’ study. Patient etiology (simple viral versus mixed infection) was determined by unanimous expert adjudication based on comprehensive clinical, laboratory and radiological assessment. Influenza strains (A or B) were detected using multiplex PCR applied to nasal swabs (Seeplex-RV15). We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. An equivocal outcome does not provide diagnostic information and is observed in ∼10% of cases. Results Out of 653 patients, 51 had positive influenza detection and unanimous expert diagnosis: 44 simple viral infections and 7 influenza with bacterial coinfections (Figure 1). Antibiotics were prescribed to all 7 cases of influenza with bacterial coinfection and to 20/44 cases adjudicated as simple viral infections, indicating an overuse rate of 45%. The assay correctly classified 40 of the 44 simple viral cases (out of the remaining 4, 2 were assigned viral with bacterial coinfection and 2 received equivocal outcomes) as well as 5 of the 7 viral with bacterial coinfection cases (the remaining 2 received equivocal outcomes) supporting the assay’s potential to reduce antibiotic overuse 5-fold (from 45% to 4/44=9%, P Conclusion The host-response assay can differentiate between simple influenza and influenza patients with bacterial coinfection, with potential to reduce antibiotic overuse. Utility studies are warranted to demonstrate that the assay can safely assist physicians in correct management of influenza patients

Background Challenges in determining the etiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant overuse of antibiotics. A new host-response assay that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind pediatric validation studies. Here we sought to evaluate its ability to differentiate bacterial from viral infection in adult COPD patients with suspicion of lower respiratory tract infection (LRTI). Methods The study population included 492 febrile adult patients prospectively recruited in “Observer”, an EU Horizon 2020 funded study (grant #684589). Patient etiology was determined by majority expert panel based on clinical, laboratory, multiplex PCR, radiological and follow-up data. We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. Results 45 out 492 adult patients prospectively recruited with suspicion of LRTI had a medical history of COPD. Of these, 20 cases were assigned as suspected viral infections and 19 as suspected bacterial infections (Figure 1). Antibiotics were prescribed to 19/19 bacterial infections and 16/20 viral infections. The assay correctly classified 19/19 bacterial infections and 12/20 viral infections, with 2 viral cases classified by the assay as bacterial and 6 receiving an equivocal outcome. These data support the assay’s potential to reduce antibiotic overuse from 16/20=80% to 8/20=40% (P=0.01). FIgure 1: Flow through of COPD patients in prospective performance validation study “Observer” Conclusion A new TRAIL/IP-10/CRP signature has potential to significantly reduce antibiotic overuse for patients with suspected LRTI and a history of COPD without missing bacterial infection. Disclosures Meital Paz, MD, MeMed Ltd. (Employee) Noa Avni, PhD, MeMed (Employee) Michal Stein, MeMed Ltd. (Employee) Liran Shani, MD, MeMed Ltd. (Employee) Tanya Gottlieb, PhD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Employee) Eran Eden, PhD, MeMed (Employee)

Background. Stroke is a major cause of morbidity and mortality during open-heart surgery. Up to 60% of intraoperative cerebral events are emboli induced. This randomized, controlled, multicenter trial is the first human study evaluating the safety and efficacy of a novel aortic cannula producing simultaneous forward flow and backward suction for extracting solid and gaseous emboli from the ascending aorta and aortic arch upon their intraoperative release. Methods. Sixty-six patients (25 females; 68 ± 10 years) undergoing elective aortic valve replacement surgery, with or without coronary artery bypass graft surgery, were randomized to the use of the CardioGard (CardioGard Medical, Or-Yehuda, Israel) Emboli Protection cannula (“treatment”) or a standard (“control”) aortic cannula. The primary endpoint was the volume of new brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI), performed preoperatively and postoperatively. Device safety was investigated by comparisons of complications rate, namely neurologic events, stroke, renal insufficiency and death. Results. Of 66 patients (34 in the treatment group), 51 completed the presurgery and postsurgery MRI (27 in the treatment group). The volume of new brain lesion for the treatment group was (mean ± standard error of the mean) 44.00 ± 64.00 versus 126.56 ± 28.74 mm 3 in the control group (p [ 0.004). Of the treatment group, 41% demonstrated new postoperative lesions versus 66% in the control group (p [ 0.03). The complication rate was comparable in both groups. Conclusions. The CardioGard cannula is safe and efficient in use during open-heart surgery. Efficacy was demonstrated by the removal of a substantial amount of emboli, a significant reduction in the volume of new brain lesions, and the percentage of patients experiencing new brain lesions.

Background A major challenge in the effective management of children with RSV infection is the clinical difficulty of distinguishing a simple viral from viral–bacterial coinfections. As a result, despite the low rates of viral–bacterial coinfection, RSV patients are often prescribed antibiotics with recent reports demonstrating more than 60% antibiotic overuse rates (Van Houten et al. 2018). Here, we examined whether a host-immune signature combining the viral-induced proteins TRAIL and IP-10 with the bacterial-induced protein CRP (ImmunoXpert; Oved et al. 2015) can distinguish simple viral from viral–bacterial coinfection in RSV patients. Methods We studied 402 febrile children enrolled as part of “Curiosity,” a prospective study designed to develop and validate the host-immune signature. Infection etiology—viral or viral-bacterial coinfection—was determined by a panel of experts following a review of patients’ clinical, laboratory, radiological, microbiological, and follow-up data. RSV strains were detected using a respiratory multiplex PCR applied to nasal swabs (Seeplex-RV15). Results Out of the 402 children with suspected acute infection 29 had a positive RSV detection (Figure 1); of them, 27 had a unanimous expert panel etiology determination: 24 viral and 3 viral–bacterial coinfections. Out of the 24 patients unanimously assigned viral by the expert panel, 13 were given antibiotics, indicating a 54% antibiotic overuse rate. The host-immune signature correctly identified all 3 viral-bacterial coinfection cases, as well as 22 out of the 24 (92%) simple viral patients. This finding supports that the signature has the potential to reduce antibiotic overuse by 6.5-fold (from an overuse of 13/24 = 54% to 2/24 = 8%, P < 0.001). Conclusion Our results demonstrate high antibiotic overuse rates for RSV patients, consistent with previous reports. The host-immune signature correctly distinguished simple viral from viral–bacterial coinfection and therefore may have the potential to aid physicians in the correct management of children with RSV infection. Implementation studies are required to evaluate its utility in safely decreasing unnecessary antibiotic use for RSV patients. Disclosures N. Mastboim, MeMed Diagnostics: Employee, Salary. K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. T. Gottlieb, MeMed Diagnostics: Employee, Salary. A. Cohen, MeMed Diagnostics: Employee, Salary. R. Navon, MeMed Diagnostics: Employee, Salary. M. Paz, MeMed Diagnostics: Employee, Salary. E. Bamberger, MeMed Diagnostics: Employee, Salary. T. Friedman, MeMed Diagnostics: Employee, Salary. L. Etshtein, MeMed Diagnostics: Employee, Salary. O. Boico, MeMed Diagnostics: Employee, Salary. I. Potasman, MeMed Diagnostics: Holding stock options, Stock options. E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. L. Shani, MeMed Diagnostics: Employee, Salary.

Background Diagnosing viral pneumonia in children is challenging. Chest radiographic imaging and clinical findings cannot reliably distinguish viral from bacterial pneumonia. Furthermore, pathogen-based diagnosis is limited by inaccessible site of infection and high asymptomatic detection rates. The objectives of this analysis were twofold: first, to establish pneumonia etiology by applying a rigorous expert panel process, and second, to evaluate whether a novel host-immune signature that integrates viral induced proteins TRAIL and IP-10 together with bacterial CRP, can accurately differentiate viral from bacterial pneumonia. Methods This analysis included 1025 febrile children enrolled in two multi-center clinical studies that evaluated the host-immune signature performance: ‘Curiosity’ study (Oved et al., PLoS One 2015) and ‘Pathfinder’ study (Srugo et al., Pediatrics 2017). Pneumonia etiology – viral or bacterial – was determined by a panel of 3 independent experts, after reviewing patients’ clinical, laboratory, microbiological, and radiological data. Only cases with majority panel assignment were included. The host-signature generated one of the three results: viral, equivocal or bacterial, based on predetermined cut-offs. Results A total of 709 children were eligible for analysis and had an expert panel etiology determination. Of them, 114 were diagnosed with pneumonia: 51 assigned viral and 63 assigned bacterial (Figure 1). The signature separated viral from bacterial pneumonia with a sensitivity of 94% (95% CI: 85%–99%) and specificity of 95% (85%–99%) with 14% equivocal test results. Out of the 51 children diagnosed with viral pneumonia by the expert panel, 40 (78%) were given antibiotics, and 43 (83%) underwent chest x-ray evaluation. The signature correctly classified 42 of these 51 viral children, indicating its potential to reduce antibiotic overuse rates by 4.4-fold (from 78% to 18%; P < 0.001) and chest x-ray examination by 4.8-fold (from 83% to 18%; P < 0.001). Conclusion The TRAIL/IP-10/CRP signature exhibits high accuracy for diagnosing viral pneumonia in children. The signature’s potential to safely decrease unnecessary antibiotics and chest radiographic imaging should be examined in future utility studies. Disclosures All authors: No reported disclosures.

Background Antibiotic overuse in LRTI is a major healthcare care problem, contributing to antimicrobial resistance. A novel assay that integrates blood levels of three immune-proteins TRAIL\IP-10\CRP was developed to assist in differentiating bacterial from viral disease. The assay exhibited high performance in blinded validation studies focusing on children. We performed a preliminary analysis of the ongoing OBSERVER study, evaluating the assay’s potential to reduce antibiotic misuse in adult patients presenting with suspicion of LRTI. Methods OBSERVER (NCT03011515) is an EU Horizon 2020 funded study (grant No. 684589), the first to validate the signature in adult LRTI patients. For every participant recruited at the emergency departments of three hospitals in Israel, we collected medical history, physical examination, routine lab, imaging, and respiratory multiplex PCR data. The assay outcomes are bacterial, viral or equivocal. Reference standard outcome of bacterial, viral, indeterminate or noninfectious, was assigned by expert panel majority adjudication. Indeterminates were excluded from the analysis. Results In this preliminary analysis, we included the first 218 patients with locked data (Figure 1). Age ranged from 18 to 96 years (mean 59.5). Clinical syndromes included: 21% pneumonia, 13% acute bronchitis, 6% COPD exacerbation, 32% upper respiratory tract infection and 16% unspecified LRTI or viral infections. The assay demonstrated high diagnostic performance for distinguishing bacterial from viral disease (Figure 2). Assay equivocal rate was 8%. In this cohort, antibiotics were prescribed to 41 of 105 patients with viral reference outcomes indicating an overuse rate of 39%, of these, 34 yielded viral index test outcomes, supporting the potential of the assay to reduce overuse by ~83%. Conclusion The TRAIL/IP-10/CRP assay demonstrated high diagnostic performance for differentiating between bacterial and viral disease. Medical literature shows that there is a big gap between guidelines antibiotic prescription recommendations and reported prescribing rates (~25% vs. 40%-50%) for suspected LRTI in adults. The use of this new assay, which has a specificity of 93% and NPV of 99%, can help to close the gap and improve adherence to the guidelines. Disclosures All authors: No reported disclosures.

Patient: Male, 45 Final Diagnosis: Endocarditis Symptoms: — Medication: — Clinical Procedure: Antibiotic treatment and aortic repair Specialty: Surgery Objective: Unusual clinical course Background: Finegoldia magna (F. magna) is a rare pathogen causing infective endocarditis (IE). Only 7 cases are documented in the literature. Case Report: We report a case of infective endocarditis in a 45-year-old male due to F. magna 2 months after a Bentall procedure. He presented with fever, dyspnea, and chest pain. Aerobic and anaerobic blood samples were drawn before empirical antibiotic treatment was initiated. A transesophageal echocardiogram (TEE) demonstrated several findings involving the prosthetic valve, including a vegetation. The patient underwent a second aortic repair procedure. Tissue cultures obtained from 2 sources in the infected area during the operation were positive for F. magna. The antibiotic regimen was changed in accordance with susceptibility testing to piperacillin/tazobactam. Two weeks after the operation, the patient was released with a recommendation for antibiotic treatment for 8 weeks. Conclusions: We report this case because F. magna in a rare pathogen causing endocarditis. This was a case of prosthetic valve F. magna IE in which the definitive diagnosis was based on tissue cultures following sterile blood cultures. Data evaluation of all F. magna IE reported cases illustrated that tissue cultures were the predominant microbiologic diagnostic tool used.

Cerebral emboli originating in the ascending aorta are a major cause of noncardiac complications following cardiac surgery. The hemodynamics of the aortic cannula has been proven to play a significant role in emboli generation and distribution. The aim of the current study was to perform a thorough numerical investigation in order to examine the effect of the design and orientation of the cannula used during cardiopulmonary bypass on the risk to develop cerebral embolism. Hemodynamic analyses compared numerical models of 27 cases consisting of six different cannula orientations, four aortic anatomies, and three cannula designs. The cannula designs included a straight-tip (ST) cannula, a moderately curved tip cannula (TIP1 ), and a sharp-angle curved cannula (TIP2 ). Outcome measures included hemodynamic parameters such as emanating jet velocity, jet velocity drop, maximal shear stress, aortic wall reaction, emboli pathlines and distribution between upper and lower vessels, and stagnation regions. Based on these parameters, the risks for hemolysis, atheroembolism, and cerebral embolism were evaluated and compared. On one hand, the jet emerging from the ST cannula generated large wall-shear stress at the aortic wall; this may have triggered the erosion and distribution of embolic atheromatous debris from the aortic arch. On the other hand, it diverted more emboli from the clamp region to the descending aorta and thus reduced the risk for cerebral embolism. The TIP1 cannula demonstrated less shear stress on the aortic wall and diverted more emboli from the clamp region toward the upper vessels. The TIP2 cannula exhibited a stronger emanating jet, higher shear stress inside the cannula, and highly disturbed flow, which was more stagnant near the clamp region. Current findings support the significant impact of the cannula design and orientation on emboli generation and distribution. Specifically, the straight tip cannula demonstrated a reduced risk of cerebral embolism, which may be pivotal in the clinical setting.

Background Stroke after open heart surgery is a major cause of morbidity and mortality. Up to 60% of intraoperative cerebral events are caused by emboli generated by manipulations of the aorta during surgery. This is the first animal study evaluating the safety and efficacy of a novel aortic cannula designed to extract solid and gaseous emboli during cardiac surgery. Methods Seven domestic pigs were connected to cardiopulmonary bypass using a CardioGard 24F aortic cannula. Three pigs that were cannulated with a standard aortic cannula were defined as controls. Several main flow and suction regimens were carried out. Osseous particles of different sizes were injected into the proximal aorta to simulate emboli. Results The CardioGard cannula demonstrated an overall emboli retrieval rate of 77%. A rate of 88.45% was demonstrated during the low-flow regimen used clinically during aortic manipulation. Gaseous and solid emboli were eliminated by suction, as demonstrated by epi-carotid ultrasound. No significant changes were observed in hemodynamic and laboratory parameters. Conclusions The CardioGard cannula is as simple to use as a regular commercially available aortic cannula, having a similar safety profile and proven efficacy in capturing intraoperative emboli.

Undernourished patients treated in general surgery departments suffer from prolonged and complicated hospitalizations, and higher mortality rates compared with well nourished patients. Pivotal information regarding patients' nutritional status and its effect on clinical outcome is lacking for cardiac surgery patients. We investigated the prevalence of malnutrition risk and its association with 30-day hospital mortality and postoperative complications.Four hundred and three patients who underwent cardiac surgery during 2008 and were screened with the Malnutrition Universal Screening Tool (MUST) on admission were enrolled. Univariate and multivariate logistic regression analyses compared the association of high and low risk for malnutrition with length of hospitalization (LOS), in-hospital and 30-day mortality, and postoperative complications. Almost 20% of the patients were found to be at high risk for malnutrition. Univariate analyses revealed higher in-hospital mortality rates (p = 0.03) and greater incidence of LOS and antibiotic treatment longer than 21 days (p = 0.002 and p = 0.04, respectively), vasopressor treatment longer than 11 days (p = 0.02), and positive blood cultures (p = 0.02) in patients belonging to the high-risk MUST group. Incorporation of the MUST in a multivariate model with the European System for Cardiac Operative Risk Evaluation (EuroSCORE) significantly improved postoperative complications prediction, as well as in-hospital and 30-day mortality, compared with the EuroSCORE alone.Malnutrition is prevalent in patients undergoing cardiac surgery, associated with higher postoperative mortality and morbidity. Preoperative MUST screening has emerged as highly relevant for enabling early diagnosis of patients at malnutrition risk, predicting postoperative mortality and morbidity, thus promoting well timed treatment. Prospective studies are needed to explore whether intervention can decrease malnutrition risk.

Evaluation of aortic proximal anastomoses in patients who have undergone coronary artery bypass surgery poses a special challenge to the interventional cardiologist during follow-up angiography procedures. We present a simple, safe, and fast technique for proximal anastomoses marking using hemostatic clips. Successful visualization of the graft marker was achieved using medium-sized hemoclips during fluoroscopy. The use of hemoclips for this procedure proved to be straightforward and required no additional surgical training.

Background Differentiating between viral and bacterial etiology is essential in order to enable the adequate use of antibiotics. Previous studies showed that TNF-related apoptosis induced ligand (TRAIL) can serve as a useful biomarker for distinguishing between bacterial and viral infections when combined with IP-10 and CRP (ImmunoXpert™). Here we evaluate the potential of a new proteomic fingerprints in children with suspected viral and bacterial infections that had a confirmed viral detection. Methods In the prospective multinational multicenter study “AutoPilot-Dx” (NCT03052088) we aim to validate the diagnostic accuracy of the ImmunoXpert™ test. Infection etiology was assigned by majority adjudication of three experts based on comprehensive clinical and laboratory investigation. Viruses were detected using multiplex-PCR applied to nasopharyngeal swabs (Allplex™, Seegene). We performed an interim analysis of the first 134 febrile children recruited that had both PCR viral detection and etiology determination. TRAIL, IP-10, CRP and ImmunoXpert™ values were measured via a Tecan EVO75 ELISA platform. Results Bacterial diagnoses were assigned by the experts to 29%, 29% and 25% of patients with adenovirus (ADV), rhinovirus (RV), and respiratory syncytial virus (RSV) detection, respectively. Children with a viral infection including ADV, RSV, and RV had significantly lower ImmunoXpert™ scores as compared with children with a bacterial infection. Notably, TRAIL levels were markedly increased in viral infections as compared with bacterial infection, irrespective of the detected virus. Conclusion Classification of viral infections correlated significantly with elevated TRAIL levels and low ImmunoXpert™ scores. The differential expression of TRAIL in response to viral vs. bacterial infections can complement molecular viral detection, appears useful in the diagnostic workup for febrile children and may reduce antibiotic misuse. Disclosures L. Etshtein, MeMed Diagnostics: Employee, Salary. N. Mastboim, MeMed Diagnostics: Employee, Salary. A. Cohen, MeMed Diagnostics: Employee, Salary. E. Simon, MeMed: Employee, Salary. O. Boico, MeMed Diagnostics: Employee, Salary. L. Shani, MeMed Diagnostics: Employee, Salary. T. Gottlieb, MeMed Diagnostics: Employee, Salary. R. Navon, MeMed Diagnostics: Employee, Salary. K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary.

Background Identifying bacterial coinfection in influenza patients can be difficult as the symptoms of simple influenza vs. mixed infections are often similar, leading to antibiotic overuse. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind validation studies. Here we sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection. Methods The study population included 653 febrile pediatric and adult patients prospectively recruited in the “Curiosity” study. Patient etiology (simple viral vs. mixed infection) was determined by unanimous expert adjudication based on comprehensive clinical, laboratory and radiological assessment. Influenza strains (A or B) were detected using multiplex PCR applied to nasal swabs (Seeplex-RV15). We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. An equivocal outcome does not provide diagnostic information and is observed in ~10% of cases. Results Out of 653 patients, 51 had positive influenza detection and unanimous expert diagnosis: 44 simple viral infections and seven influenza with bacterial coinfections (Figure 1). Antibiotics were prescribed to all seven cases of influenza with bacterial coinfection and to 20/44 cases adjudicated as simple viral infections, indicating an overuse rate of 45%. The assay correctly classified 40 of the 44 simple viral cases (out of the remaining four, two were assigned viral with bacterial coinfection, and two received equivocal outcomes) as well as five of the seven viral with bacterial coinfection cases (the remaining two received equivocal outcomes) supporting the assay’s potential to reduce antibiotic overuse 5-fold (from 45% to 4/44 = 9%, P < 0.001). Conclusion The host–response assay can differentiate between simple influenza and influenza patients with bacterial coinfection, with potential to reduce antibiotic overuse. Utility studies are warranted to demonstrate that the assay can safely assist physicians in correct management of influenza patients. Disclosures M. Paz, MeMed Diagnostics: Employee, Salary. K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. T. Gottlieb, MeMed Diagnostics: Employee, Salary. A. Cohen, MeMed Diagnostics: Employee, Salary. R. Navon, MeMed Diagnostics: Employee, Salary. N. Mastboim, MeMed Diagnostics: Employee, Salary. E. Bamberger, MeMed Diagnostics: Employee, Salary. T. Friedman, MeMed Diagnostics: Employee, Salary. L. Etshtein, MeMed Diagnostics: Employee, Salary. O. Boico, MeMed Diagnostics: Employee, Salary. I. Potasman, MeMed Diagnostics: Holding stock options, Stock options. E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. L. Shani, MeMed Diagnostics: Employee, Salary.

The generation of emboli during cardiopulmonary bypass (CPB) is profoundly affected by the hemodynamic properties of the aortic cannula used in the current study. The aim of the current work was to numerically investigate the hemodynamic efficiency and feasibility of a novel, backward suction cannula (BSC), designed to drastically reduce the potential risk for cerebral emboli (CEP). In line with the standard cannulae, the BSC provides oxygenated blood from the CPB machine through its primary lumen. However, the unique feature of the BSC lies in its secondary lumen, which is used to suck blood and embolic matter back from the surgical field to the CPB machine for filtration. Analysis included a numerical investigation of the hemodynamic characteristics of 44 different models, encompassing various anatomic orientations, cannula types, cannula orientations and flow conditions. Hemodynamic efficacy and CEP were assessed via trajectories of particle released from the surgical region, while the cannula feasibility was evaluated through potential for atheroembolism (AP) and index for hemolysis (IH). Differences between the investigated cannulae in terms of these measures were tested using analyses of variance tests (ANOVAs). Results indicate that the BSC exhibited a significant improvement of the cannula performance in terms of CEP with no significant change in the risk for other hemodynamic complications, such as hemolysis or atheroembolism (AP and IH). These findings suggest the advantageous use of the BSC in the clinical setting for its potential to diminish the risk for cerebral emboli, which presents the most pertinent cause of noncardiac complications following open heart surgery.

Introduction: thoracic aortic graft infection is a rare and devastating complication of aorta replacement surgery with an incidence range of 0.9–1.9%. Prosthetic aortic graft infections represent a major diagnostic and therapeutic challenge. Despite latest advancements in imaging and microbiological investigations there are still no agreed criteria to confirm the diagnosis. case report: We present a case of late onset culture negative thoracic aortic graft infection in a caucasian 65-year-old male, nine years after aortic replacement due to acute aortic dissection. conclusion: culture-negative vascular graft infection has not been described as a clinical entity so far. review of current literature and Issues of diagnosis and management will be discussed.