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Providing candid advice on the ups and downs of entrepreneurship, this book interweaves the world of tech start-ups, the American immigrant experience, and the realities of running a business with your life partner. Across two decades as entrepreneurs, Elma and Dov Levy faced economic recessions, government shutdowns, work-life balance issues, leadership conflicts, and the emotions of letting go of their company Dovel Technologies - a technology consulting firm that they grew from a space in their attic to a multimillion-dollar operation with major government contracts. In this conversational and practical book they share insights on: How next-generation entrepreneurs can develop business relationships and networking skills, and maintain a high level of risk tolerance and manage risks strategically, including how and when to scale the business. How to stay true to guiding principles as co-owner spouses and woman-owned business entrepreneurs. What trends and opportunities to watch out for in a post-COVID-19 world. Aspiring entrepreneurs, growth-focused founders, family business owners, and government and technology professionals will especially value the Levys' business and personal success stories, with guidance on how to manage a marriage and business simultaneously, creating boundaries with a home office, and showing mutual respect in the boardroom. © 2023 Elma Levy and Dov Levy. All rights reserved.
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Background: QT interval prolongation is common in critically ill patients and is associated with increased mortality. However, the predictive value of a prolonged corrected QT interval (QTc) for myocardial injury and long-term mortality among patients hospitalized with COVID-19 infection is not well known. Purpose: To evaluate the association of prolonged QTc with myocardial injury and with 1-year mortality among patients hospitalized with COVID-19 infection. Methods: A total of 335 consecutive patients hospitalized with COVID-19 infection were prospectively studied. All patients underwent a comprehensive echocardiographic evaluation within 48 hours from admission. Using the Bazett formula, the QTc interval was calculated from the first ECG tracing recorded at the ER. QTc ≥440 msec in males and ≥450 msec in females was considered prolonged. Patients with elevated cardiac biomarkers and/or echocardiographic signs of myocardial dysfunction were considered to have myocardial injury. The predictive value of QTc prolongation for myocardial injury was calculated using a multivariate binary regression model. One-year mortality rate of patients with and without QTc prolongation was compared using the log-rank test, and a multivariate Cox regression model adjusting for multiple covariates was performed to evaluate the 1-year mortality risk. Results: One-hundred and nine (32.5%) patients had a prolonged QTc. Compared to patients without QTc prolongation, patients with prolonged QTc were older (70±14.4 vs 62.7±16.6, p <0.001), had more comorbidities, and presented with a more severe disease. Prolonged QTc was an independent predictor for myocardial injury (adjusted HR 2.07, 95% CI 1.22-3.5;p=0.007). One-year mortality of patients with prolonged QTc was higher than those with no QTc prolongation (40.7% vs 16.9;p <0.001, adjusted HR 1.85[1.2-2.84];p=0.005). Compared to patient without QTc prolongation and no myocardial injury, the adjusted 1-year mortality risk was highest in patients with prolonged QTc and myocardial injury (HR 6.63, 95% CI 2.28-19.3;p=0.001), followed by patients with QTc prolongation without myocardial injury (HR 6.12 95% CI 1.83-20.49;p=0.003), and patients with myocardial injury without QTc prolongation (HR 4.95 95% CI 1.83-20.49.;p=0.003). Conclusion: Prolonged QTc is an independent risk factor for both myocardial injury and 1-year mortality among patients hospitalized with COVID-19 infection. (Figure Presented).
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Introduction: Treatment-free remission (TFR) is an emerging treatment goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). Current evidence shows that 40%-60% of patients relapse while in TFR;and nearly all regain response once tyrosine kinase inhibitors (TKIs) treatment are reinitiated. However a robust predictor of prolonged TFR has not been reported yet. Considering real-life setting, 2 key factors may affect TFR outcome if not properly done: Access to serial molecular monitoring at optimal timepoints and quality laboratory terms as accuracy, sensitivity and rapid results. This motivated the creation of the AST study in our region to guarantee adequate molecular monitoring for TFR in Argentina and characterize new prognostic biomarkers helpful to identify more accurately patients who will be able to sustain TFR. We aimed to assess the proportion of patients with sustained major molecular response (MMR) after TKIs discontinuation and define precise conditions for stopping treatment. Methods: This prospective, multicentre Argentina Stop Trial (AST) trial is recruiting chronic phase CML patients under TKI treatment for at least ≥ 4 years, in DMR (≥MR4.0) sustained for ≥ 2 years in standardized laboratory, confirmed typical BCR-ABL1 transcripts b3a2 and/or b2a2 and aged > 18 years. Molecular tests are centralized in 2 harmonized laboratories and performed monthly for the first 6 months, every 2 months until the first year, and every 3 months during the second year. If patients lost MMR, TKI was restarted immediately. Molecular relapse Free Survival was estimated by Kaplan-Meier method. Difference between survival variables was evaluated through log-rank test. Multivariate analysis was performed through Cox proportional hazards model. The cutoffs of the numerical variables were considered according to the log-rank test. Results: Between February 2019 and July 2020, we evaluated 50 CML patients of whom 46 were enrolled from 7 centers in Argentina and 4 were screening failures. Recruitment was interrupted due to COVID-19 pandemic. Patient median age was 57.5 years (range 24-85). Before discontinuation, TKI treatment was as follows: Imatinib 37/46 (80%), Nilotinib 5/46 (11%) and Dasatinib 4/46 (9%), 2G-TKI as 1st line, 11% of the patients received non-branded treatment. Sokal risk score showed to be low in 22 patients (48%), intermediate in 14 (30%) and high in 10 (22%). Median follow-up was 10 months (range 4-17) and the estimated molecular relapse-free survival was 80.2% (95%CI 69-93) at 6 months Fig 1. Longer DMR durations before discontinuation were associated with increased probability of maintaining response at 6 and 12 months: 83.2% for patients who had >54 months in DMR vs 70% with <54 months and 72% vs 23.3% respectively (p=0.0453) Fig 2. Cox multivariate analysis was performed including different variables as age at diagnosis, time in DMR, time in TKI previous to discontinuation and Sokal risk. The only significant variable associated to improved prognosis was time in DMR (HR 2.8 95%CI 1.002-8.07 p=0.0495). Our cohort had a long time on TKI treatment previous to discontinuation, median 10.5 years (4.16-17.5) probably considering it a favorable factor for the high TFR rates described at 6 months. Among the 46 patients included, 15 (33%) lost MMR, all restarted treatment with the same TKI used before discontinuation, 12/15 (80%) regained MMR with a median time of 3 months (range1-8) and 9/15(60%) obtained MR 4.0 with a median time of 3 months (range1-5). Conclusion: This is the first multicenter study of TKI discontinuation in CML patients in Argentina showing that TKI can be safely discontinued in those who achieve and maintain a DMR before discontinuation. We observed high rates of molecular relapse free survival, although longer follow-up is needed. We must continue with this approach for patients participating in TFR trials or TFR programs in order to decrease the risk of relapse and make this goal a fact in our region. This discontinuation study will allow in a near futu e significant saving of economic resources and might improve patients quality of life specially in those who are currently experiencing treatment adverse events. [Formula presented] Disclosures: Pavlovsky: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS: Speakers Bureau;Pfizer: Speakers Bureau;Pint Pharma: Speakers Bureau. Varela: Novartis: Consultancy, Speakers Bureau. Pavlovsky: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Varifarma: Speakers Bureau. Moiraghi: BMS: Speakers Bureau;Novartis: Speakers Bureau.
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Introduction: Red blood cell (RBC) rich vs fibrin rich clots have different mechanical properties and greater knowledge about clot composition in the context of clinical, imaging, and procedural factors in mechanical thrombectomy (MT) may help with procedural optimization. The EXCELLENT Registry (NCT03685578) is a prospective, global, multi-center, observational registry of EmboTrap as the first line MT device for large vessel occlusion (LVO). We present an interim analysis of clot collected per pass in the registry. Methods: Five hundred thirty-three clot specimens from 376 subjects were collected by 20 sites and sent for analysis by independent Central Labs under standardized protocol. Analysis was interrupted by COVID-19, but the labs were fully operational as of June 2020 and on track to deliver results for 300 subjects in Q4. At the time of abstract submission, composition data for 234 clots from 163 subjects was available. All available data will be presented at the time of the conference. Results: Cardioembolic etiology (n=100) was associated with lower RBC (40.2 vs 47.2%) and higher fibrin content (31.7 vs 26.7%) compared to large artery disease (n=12). Hyperdense/vessel susceptibility sign (78+, 24-, per independent imaging core lab) corresponded to higher mean RBC content (44.4 vs 34.9%). Treatment with IV tPA (60+, 91-) had no clear impact on clot composition (42.3 vs 40.6% RBC;30.4 vs 30.0% fibrin). Notably, clots retrieved with the first 2 passes of were more RBC rich (42.1 vs 28.0%) and clots retrieved in higher passes had a higher average fibrin content (35.5 vs 29.6%) suggesting that higher fibrin content leads to greater refractoriness. Conclusions: Clot density/susceptibility on baseline imaging, stroke etiology and number ofthrombectomy passes were associated with differential clot composition. These findings may havepotential implications for the development of better MT strategies.