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  • Oxford University Press (OUP)  (6)
  • 1
    In: European Heart Journal, Oxford University Press (OUP), Vol. 42, No. 17 ( 2021-05-01), p. 1676-1684
    Abstract: The benefit of prophylactic implantable cardioverter-defibrillator (ICD) is not uniform due to differences in the risk of life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) and non-arrhythmic mortality. We aimed to develop an ICD benefit prediction score that integrates the competing risks. Methods and results The study population comprised all 4531 patients enrolled in the MADIT trials. Best-subsets Fine and Gray regression analysis was used to develop prognostic models for VT (≥200 b.p.m.)/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF). Eight predictors of VT/VF (male, age  & lt; 75 years, prior non-sustained VT, heart rate  & gt; 75 b.p.m., systolic blood pressure  & lt; 140 mmHg, ejection fraction ≤ 25%, myocardial infarction, and atrialarrhythmia) and 7 predictors of non-arrhythmic mortality (age ≥ 75 years, diabetes mellitus, body mass index  & lt; 23 kg/m2, ejection fraction ≤ 25%, New York Heart Association ≥II, ICD vs. cardiac resynchronization therapy with defibrillator, and atrial arrhythmia) were identified. The two scores were combined to create three MADIT-ICD benefit groups. In the highest benefit group, the 3-year predicted risk of VT/VF was three-fold higher than the risk of non-arrhythmic mortality (20% vs. 7%, P  & lt; 0.001). In the intermediate benefit group, the difference in the corresponding predicted risks was attenuated (15% vs. 9%, P  & lt; 0.01). In the lowest benefit group, the 3-year predicted risk of VT/VF was similar to the risk of non-arrhythmic mortality (11% vs. 12%, P = 0.41). A personalized ICD benefit score was developed based on the distribution of the two competing risks scores in the study population (https://is.gd/madit). Internal and external validation confirmed model stability. Conclusions We propose the novel MADIT-ICD benefit score that predicts the likelihood of prophylactic ICD benefit through personalized assessment of the risk of VT/VF weighed against the risk of non-arrhythmic mortality.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2001908-7
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  • 2
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 10, No. 7 ( 2021-08-17), p. 757-765
    Abstract: Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children. Methods An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children & lt;18 years across Israel (~75% of Israeli hospitals). Results Overall, 1007 cases (439 outpatients and 568 hospitalized) identified represent 0.35% of pediatric COVID-19 nationwide (n = 291 628). Of hospitalized cases, 464 (82%), 48 (8%), and 56 (10%) had mild, moderate/severe, and PIMS disease, respectively. The mean ± SD age was 5.6 ± 6.4 years. In mild, moderate/severe, and PIMS disease, 55%, 23%, and 4% of patients were & lt;1 year old, respectively. Obesity was reported in 1%, 4%, and 13% of patients, respectively (P & lt; .001). The most common symptom was fever in 67%, 60%, and 100%, respectively, whereas respiratory symptoms were documented in 33%, 41%, and 38% of patients, respectively. Lymphopenia was recorded in 25%, 60%, and 86% of cases, respectively. PIMS diagnosis was mainly serology-based (in 59%). Gastrointestinal symptoms, cardiovascular involvement, rash, and conjunctivitis were noted in 82%, 61%, 57%, and 34% of PIMS episodes, respectively. Elevated C-reactive protein (100%), ferritin, troponin, D-dimer, low albumin, and thrombocytopenia were common in PIMS. Echocardiography revealed pathological findings in 33% of patients. PIMS mainstay treatment included corticosteroids (77%) and intravenous immunoglobulin (53%). No mortality was recorded. Conclusions At a national level, pediatric COVID-19 is mild, even in hospitalized cases, with only a third presenting with respiratory involvement. PIMS is rare, but necessitates a high index of suspicion, and with suitable treatment prognosis is favorable.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2668791-4
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S22-S23
    Abstract: Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2; p & lt; 0.001). Likelihood of severe outcome increased significantly (p & lt; 0.001) with higher scores. The signature’s area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p & lt; 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p & lt; 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p & lt; 0.001; Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p & lt; 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation. Disclosures Alon Angel, n/a, MeMed (Employee, Shareholder) Niv Samuel Mastboim, BSc, MeMed (Employee, Shareholder) Oded Shaham, PhD, MeMed (Employee, Shareholder) Tahel Ilan Ber, MD, MeMed (Employee, Shareholder) Roy Navon, MSc, MeMed (Employee, Shareholder) Einav Simon, PhD, MeMed (Employee, Shareholder) Michal Rosenberg, PhD, MeMed (Employee) Yael Israeli, PhD, MeMed (Employee) Mary Hainrichson, PhD, MeMed (Employee, Shareholder) Noa Avni, PhD, MeMed (Employee) Eran Reiner, MD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Board Member, Employee, Shareholder) Ilya Kagan, MD, MeMed (Scientific Research Study Investigator) Shaul Lev, M.D, MeMed (Scientific Research Study Investigator) Dror Diker, MD, MeMed (Scientific Research Study Investigator) Amir Jarjou’i, MD, MeMed (Scientific Research Study Investigator) Ramzi Kurd, MD, MeMed (Scientific Research Study Investigator) Guy Danziger, MD, MeMed (Scientific Research Study Investigator) Cihan Papan, MD, MeMed (Scientific Research Study Investigator) Sergey Motov, MD, MeMed (Scientific Research Study Investigator) Maanit Shapira, Ph.D, MeMed (Scientific Research Study Investigator) Tanya Gottlieb, PhD, MeMed (Employee, Shareholder) Eran Eden, PhD, MeMed (Board Member, Employee, Shareholder)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S761-S761
    Abstract: Identifying infectious etiology is often challenging, yet essential for patient management, including antibiotic use. Studies have shown that a host signature comprising TNF-related apoptosis induced ligand (TRAIL), interferon gamma induced protein-10 (IP-10) and C-reactive protein (CRP) accurately differentiates bacterial from viral infection with negative predictive value & gt;98%. Performance data was lacking in chronic obstructive pulmonary disease (COPD) patients with suspected lower respiratory tract infection (LRTI). Methods Adults aged & gt;18 years with suspected LRTI were prospectively recruited at 3 medical centers (OBSERVER; grant #684589; NCT003011515). Reference standard infection etiology was adjudicated by 3 independent experts based on clinical, laboratory, microbiological, radiological and follow-up data. Host signature generates a bacterial likelihood score (0-100), providing three results: viral (0-35), equivocal (35-65) and bacterial (65-100). Experts were blinded to the signature result. Results Out of 583 adults recruited with suspected LRTI, 422 met infectious criteria, of whom 48 had a recorded history of COPD. 19 cases were adjudicated by the experts as bacterial, 14 as viral and 15 were indeterminate (Figure 1). The mean age was 68.2 years (standard deviation 12.3); 33 (68.8%) presented after two or more days of symptoms and 38 (79.2%) were hospitalized for a median of 6 days. 15 (31.2%) were female. For the patients adjudicated bacterial or viral labels (n=33), the discharge diagnoses were: COPD exacerbation, 12 cases (36.4%); pneumonia, 12 cases (36.4%) (3.0%); acute bronchitis, 2 cases (6.1%); upper RTI ,1 case; unspecified viral infection 1 case (3.0%); or other, 5 cases (15.2%). Host signature correctly classified all 19 bacterial cases and 8 of the viral cases, providing accurate etiology labels for 27/33 COPD patients with reference standard labels (81.8%). The remaining 6 viral cases received equivocal scores (18.2%). COPD patient enrollment and etiology labels in the Observer study Conclusion Host signature accurately differentiates between bacterial and viral infections in patients with COPD history, supporting potential to improve management among these patients frequently admitted for RTIs. Disclosures Michal Stein, MeMed (Employee) Meital Paz, MD, MeMed (Employee) Tanya Gottlieb, PhD, MeMed (Employee, Shareholder) Eran Barash, MA, MeMed (Employee) Roy Navon, MSc, MeMed (Employee, Shareholder) Einat Moscoviz, BSc+ MBA, MeMed (Employee) Tahel Ilan Ber, MD, MeMed (Employee, Shareholder) Liran Shani, MD, MeMed (Employee) Olga Boico, PhD, MeMed (Employee) Einav Simon, PhD, MeMed (Employee, Shareholder) Noa Avni, PhD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Board Member, Employee, Shareholder) Eran Eden, PhD, MeMed (Board Member, Employee, Shareholder)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 5
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi19-vi20
    Abstract: There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E–mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer. METHODS This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologically-confirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. RESULTS Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%). CONCLUSIONS Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E‒mutated HGG or LGG, with manageable AEs and no new safety signals.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2094060-9
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
    In: The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Oxford University Press (OUP)
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2043927-1
    SSG: 12
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