tbuckley/cabot-search huggingface dataset:
Abstract 11647: Influence of Hypercoagulability and Impaired Fibrinolysis on Occurrence of Acute Myocardial Infarction and Prognostic Implication Following Percutaneous Coronary Intervention
Authors: Hyun Kuk Kim, Seung Hun Lee, Yongwhi Park, Young-hoon Jeong, Jinyong Hwang, Jong-Hwa Ahn, Udaya Tantry, Paul A Gurbel
Journal: Circulation (2021)

Introduction: Although a plaque damage such as rupture is quite commonly observed, catastrophic event with clinical symptoms is not common in real practice. Hypothesis: Hypercoagulability and impaired fibrinolysis can be associated with the risk of coronary thrombosis and long-term clinical prognosis in patients with coronary artery disease (CAD). Methods: CAD patients who underwent percutaneous coronary intervention (PCI) (n=2,705) were enrolled (presented with acute myocardial infarction [AMI], 47.8%). Global hemostatic properties were evaluated with thromboelastographic assay (TEG ® ) showing hypercoagulability (maximal amplitude [MA]: platelet-fibrin clot strength) and impaired fibrinolysis (LY 30 : percent lysis 30 minutes after maximal clot strength). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, myocardial infarction, or stroke. Results: Patients presented with AMI showed higher MA (66.5±7.8 vs. 65.3±7.2 mm, P&lt;0.001) and lower LY 30 levels (1.0±2.5% vs. 1.2±2.2%, P=0.009) compared with non-AMI patients. Combined criteria of ‘MA≥68 mm’ and ‘LY 30 &lt;0.2%’ increased the risk of AMI occurrence by 1.7-fold. During 4-year follow-up, MACE was associated with ‘MA≥68 mm’ (hazard ratio [HR] 1.447, 95% confidential interval [CI] 1.051-1.992, P=0.024) and ‘LY 30 &lt;0.2%’ (HR 1.328, 95% CI 0.965-1.828, P=0.081), respectively. In multivariate analysis, patients with ‘MA≥68 mm’ and ‘LY 30 &lt;0.2%’ showed an increased risk of MACE compared to those with ‘MA&lt;68 mm’ and ‘LY 30 ≥0.2%’ (adjusted HR 1.863, 95% CI 1.191-2.913, P=0.006) (Figure 1). Subgroup analysis showed that this trend was consistent irrespective of baseline demographics and lesional characteristics. Conclusions: Hypercoagulability and impaired fibrinolysis were more frequently observed in AMI patients. In addition, these properties were significantly associated with post-PCI clinical prognosis.
Use of Endpoints in Phase III Randomized Controlled Trials for Acute Myeloid Leukemia over the Last 15 Years: A Systematic Review
Authors: Moazzam Shahzad, Muhammad Arslan, Sibgha Gull Chaudhary, Raheel S Siddiqui, Ezza Tariq, Faryal Murtaza, Sara Shahid, Raza Ur Rahman, Iqra Anwar, Ali Hussain, Abdulraheem Yacoub, Peiman Hematti, Tara L. Lin, Joseph P. McGuirk, Muhammad Umair Mushtaq
Journal: Blood (2021)
Melphalan 140 Mg/m 2 As Conditioning Regimen for Autologous Stem Cell Transplant- Comparative Study from a Tertiary Centre in Southern India
Authors: Sani Kodathumuriyil Sunny, Nikhil Krishna Haridas, Remya Sudevan, Ambily Nadaraj, Manoj Unni, Rema Ganapathy, Ullas Mony, Neeraj Sidharthan
Journal: Blood (2021)
Oligoblastic (&amp;lt;20%) Myeloid Neoplasms with <i>KMT2A</i> (<i>MLL</i>) Rearrangement Show Significant Overlap with Acute Myeloid Leukemia (AML) and Should be Regarded As AML
Authors: Sergej Konoplev, Guilin Tang, Xiaoqiong Wang, Wei Wang, Beenu Thakral, Jie Xu, Sherry A. Pierce, Jeffrey L. Jorgensen, Farhad Ravandi, Ghayas C. Issa, Olga Pozdnyakova, Sa A Wang, Robert P. Hasserjian
Journal: Blood (2021)
Realmind: A Prospective, Multicenter, Observational Study of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Starting Second- or Third-Line Therapy and Not Receiving Autologous Stem Cell Transplant
Authors: Christopher R. Flowers, John M. Burke, Mirko Vukcevic, Susan Snodgrass, Shreekant Parasuraman, Thomas Büchele, Nuwan C. Kurukulasuriya
Journal: Blood (2021)
Combination of azacytidine and bortezomib show synergistic cytotoxicity in glioma
Authors: Shikha Gaur, Yun Yen
Journal: Cancer Research (2008)

4025  Traditional treatment of Glioblastoma Multiforme (GBM) with surgery and radiotherapy have limited efficacy and adjuvant chemotherapy offers only a modest survival benefit in some patients. One of the mechanism responsible for impaired apoptosis in cancer results from epigenetic silencing of tumor suppressor or proapoptotic genes occurring by hypermethylation of promoter region of the gene. Inhibitors of DNA methylation induce reexpression of silenced genes and restore cell growth control or induce apoptosis. The other novel therapeutic target is the ubiquitin/proteasome pathway, a key element in the cell cycle progression and cell survival. We studied the effect of combination ofproteasome inhibitor (bortezomib) and demethylating agent (azacytidine) in glioblastoma resistance. We treated glioma cell lines U251T and U87MG (sensitive) with azacytidine (1 -5 µM) and bortezomib (0.05-0.3 µM) simultaneously for 24h. Cell titer one solution proliferation assay was used as the end point for cell proliferation. The IC50 values and combination indices (CI) were derived using Calcusyn software (Biosoft, Cambridge, UK). U251T and U87MG cell lines showed a strong synergy with a combination index of 0.3 and 0.4 respectively. The combination of azacytidine and bortezomib in the same dosage range also showed a strong synergistic effect (CI=0.19) in T98G Glioma cell line (resistant). We further evaluated the antitumor efficacy of bortezomib and/or azacytidine in U87-MG human glioma carcinoma model. U87-MG cells (1x106) were inoculated into balb/c nude mouse via s.c. injection. When the average tumor size reached ~100 mm3 (80-125 mm3), animals were randomly divided into 4 groups and treated with 0.9%NaCl (group 1), 5 mg/kg azacytidine i.v. (group 2), 1 mg/kg bortezomib i.v. (group 3), azacytidine & bortezomib (group 4) twice weekly. A significant decrease in tumor size was observed in animals treated with azacytidine alone (p
PATH-32. EXTENT, PATTERN, AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION: DOES IT DIFFER BETWEEN GLIOBLASTOMA AND IDH-WILDTYPE/TERT-MUTATED ASTROCYTOMA?
Authors: Nico Teske, Philipp Karschnia, Jonathan Weller, Sebastian Siller, Mario M Dorostkar, Jochen Herms, Louisa von Baumgarten, Jörg-Christian Tonn, Niklas Thon
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The cIMPACT-NOW update 6 introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. METHODS We searched the institutional database for patients with: 1.) glioblastoma defined by histopathology; and 2.) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. RESULTS We identified 224 patients with glioblastoma diagnosed based on histopathology, and 71 patients with IDHwt astrocytoma with pTERTmut (32 astrocytomas WHO grade II and 39 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two groups as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two groups. Surgery was associated with improved overall survival in IDHwt astrocytoma with pTERTmut. In patients treated with radiochemotherapy or radiotherapy, higher numbers of methylated CpG sites were associated with favourable outcome in both groups. CONCLUSION Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both groups, higher numbers of methylated CpG sites are associated with favourable outcome when radio/chemotherapy is administered. Surgery may form the basis for favourable outcome.
Real-World Effectiveness of Bortezomib Plus Dexamethasone in Patients with t(11;14) Positive Multiple Myeloma
Authors: Nnadozie Emechebe, Shaji Kumar, Hartmut Goldschmidt, Maria-Victoria Mateos, Juan Du, Kihyun Kim, Giampaolo Merlini, Meletios A. Dimopoulos, Heinz Ludwig, Hiroshi Handa, Carlos Fernandez de Larrea, Donna E. Reece, Wenming Chen, Noopur S. Raje, Sudeep Karve, Emma Arriola, Jeremy A. Ross, Brian G.M. Durie
Journal: Blood (2021)
Abstract 12644: Clinical Features and Outcomes by Systemic Ventricle Morphology in Adult Fontan Patients
Authors: Jessica M Hong, Vidhushei Yogeswaran, Christopher Anigwe, Anita J Moon-Grady, Ian S Harris, peter kouretas, Vaikom S Mahadevan, Anushree Agarwal
Journal: Circulation (2021)

Introduction: Single ventricle physiology is commonly encountered in patients after Fontan palliation. However, limited data exists on the differences in clinical characteristics and long-term outcomes in adults with systemic left ventricular morphology (SLV) compared to systemic right ventricular morphology (SRV). Methods: Retrospective review of medical records from a tertiary medical center for 2010-2018 identified 191 Fontan patients ≥ 18 years of age for whom ventricular morphology data was available. Results: Of 191 patients, 62 (32%) had SRV and 129 (68%) had SLV. Mean age was 28.9 ± 9.1 years and mean age at the time of Fontan palliation was 6.4 ± 6.7 years. Patients with SLV were older (30.9 ± 9.6 years vs. 24.7 ± 6.0 years) and more likely to have classic atriopulmonary connection (17% vs. 2%). Differences in adverse outcomes by ventricular morphology are shown in the figure. After adjusting for age, patients with SRV were more likely to have atrioventricular valve regurgitation (adjusted odds ratio 3.42, 95% confidence interval 1.56-7.52, p=0.002). There were no significant age-adjusted differences between SRV and SLV patients for NYHA class, arrhythmia/pacemaker placement/implantable cardioverter-defibrillator (ICD) placement, heart failure hospitalization, thromboembolic complications, cirrhosis, protein-losing enteropathy, Fontan revision, or death. Data from cardiac catheterization, cardiopulmonary exercise testing, and liver function tests showed no significant differences. Conclusion: Adverse outcomes among adult recipients of the Fontan procedure did not differ significantly based on ventricular morphology. Further multicenter studies will be necessary to understand finer differences in SRV and SLV pathophysiology and eventually the impact of ventricular modeling on long term outcomes as the adult Fontan population continues to age.
Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients
Authors: Matteo Lambertini, Luca Boni, Andrea Michelotti, Emanuela Magnolfi, Alessio Aligi Cogoni, Anna Maria Mosconi, Monica Giordano, Ornella Garrone, Grazia Arpino, Francesca Poggio, Paola Cinacchi, Claudia Bighin, Piero Fregatti, Paolo Pronzato, Eva Blondeaux, Lucia Del Mastro
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor–positive disease. There are controversial data on its fertility preservation potential. Methods The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results Of 281 randomly assigned patients, 80.4% had hormone receptor–positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor–positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92). Conclusions Final analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor–positive disease.
Serological Response Following BNT162b2 Anti-Sars-Cov-2 mRNA Vaccination in Hematopoietic Stem Cell Transplantation Patients
Authors: Imma Attolico, Francesco Tarantini, Paola Carluccio, Claudia Schifone, Mario Delia, Vito Pier Gagliardi, Tommasina Perrone, Francesco Gaudio, Chiara Longo, Annamaria Giordano, Nicola Sgherza, Paola Curci, Rita Rizzi, Alessandra Ricco, Antonella Vita Russo Rossi, Francesco Albano, Angela Maria Vittoria Larocca, Luigi Vimercati, Silvio Tafuri, Pellegrino Musto
Journal: Blood (2021)
Phase 1/2, Open-Label, Dose Escalation, Dose Expansion Study of Menin Inhibitor DSP-5336 in Adult Patients (pts) with Acute Leukemia with and without <i>Mixed-Lineage Leukemia</i> (<i>MLL</i>)-Rearrangement or Nucleophosmin 1 (<i>NPM1</i>) Mutation
Authors: Naval Daver, John Affinito, Hongliang Cai, Hanna Dobrowolska, Edward Dow, Ken Eguchi, Gregory Song, Jay Stoudemire, Akinobu Watanbe, Philip Komarnitsky
Journal: Blood (2021)
Abstract 13350: Pulmonary Embolism Readmission Trend Over the Years: A National Readmission Database Study
Authors: Hafeez Shaka, Sujitha Velagapudi, Mukunthan Murthi, Hernan G. M Marcos-Abdala, Ramtej Atluri, Genaro R Velazquez
Journal: Circulation (2021)

Introduction: Acute pulmonary embolism(PE) is known to be associated with significant short term and long term complications. However with evolution of PE management, the outcomes of PE related complications and need for readmission has not been well studied. Our aim of this study is to see the trend in readmissions in PE patients from the years 2010 to 2018. Methods: We utilized the National Readmission Database from 2010 to 2018 to identify hospitalized patients with a principal diagnosis of acute pulmonary embolism. Identified the total number of readmissions for acute PE from 2010 to 2018. Multivariate cox regression model was used to identify independent predictors of readmission. Results: The number of patients with 30-day readmissions have gradually increased from 14,508 in 2010 to 19,703 in 2018. The proportion of females admitted was higher than males in all years.The 30-day all cause readmission after principal admission for PE decreased from 11.2% to 9.7% from 2010 to 2014 but increased to 11.8% in 2018 (p&lt;0.001). Risk adjusted readmission specific for PE showed a decrease from 1.2 to 1% (p=0.023) from 2010 to 2018, with the proportion decreasing from 11.9% to 9.5% during the same period. There was no significant difference in the inpatient mortality (p=0.382) and length of stay (p=0.658) during the study period. There was an increasing trend in the total hospital charges from 2010 (13,374$) to 2018 (15,104$) but the difference was not statistically different (p=0.086). Conclusion: Our study suggests that there is a statistically significant decrease in PE specific readmission, with a decrease followed by an increase in all-cause admission after a PE. There is also no significant difference in mortality and length of stay. These findings warrant further studies to elucidate the mechanism for decrease PE-specific readmission but possible causes for the increase in all-cause readmission in the hope of optimizing management and continuing improving outcomes.
An Inpatient COVID-19 Prophylaxis Protocol and Its Outcomes: Adherence and Efficacy
Authors: Adrienne Kaufman, Yael Kusne, Molly Klanderman, Heidi E. Kosiorek, Thomas Oliver, Miguel Gonzalez-Velez, Robert D. McBane, Waldemar E. Wysokinski, Damon E. Houghton, Leslie Padrnos
Journal: Blood (2021)
A strategy for NHS Scotland focused on reducing emissions and enhancing wellbeing
Authors: Elaine Mulcahy
Journal: BMJ (2021)

In 2019, the Scottish Government announced its ambition for NHS Scotland to become net-zero by 2045. After much anticipation in the lead up to COP26 in Glasgow, the NHS Scotland Climate Emergency and Sustainability Strategy was published on 10 November 2021 and opened for consultation until February 2022.1

The strategy raises the bar on the initial target by bringing forward the date for achieving net-zero emissions to 2040. Fundamental to the goal of reducing emissions is an ambition to do this is in a way that enhances wellbeing and reduces health inequalities: “A health service that improves the opportunities, life chances, health and wellbeing of every citizen in our country and fully contributes to a more cohesive, resilient and net-zero society in a just way that contributes of population wellbeing and a reduction in health inequalities.” 

Achieving such an ambitious aim will require commitment across all elements of the health service, including the people it serves. Significant progress in reducing emissions will be made through a shift from fossil fuels to renewables, and improving infrastructure and facilities to make them more energy efficient. The expectations of the healthcare workforce, patients, and visitors of the way in which the service operates will also need to adjust to enable the transformation to more sustainable …
Abstract 11101: The Creation and Early Outcomes of a Nurse Led, IV Diuretic Clinic in a Rural Setting
Authors: Susan D'Anna, Margaret Emmons, Deborah Cantlin, Carolyn DeMark, Kim Ambrose, Amanda Racine, Lauren Gilstrap
Journal: Circulation (2021)

Introduction: IV diuretic clinics are becoming an increasingly common way to manage HF in the outpatient setting. Limited data exists for the effectiveness and safety of these nurse led clinics when operating in rural areas. This is important because rural HF patients have poorer outcomes and limited access to HF-focused providers. This study aims to describe the development, implementation and outcomes of a nurse led, rural IV diuretic clinic. Methods: We began by conducting stakeholder interviews, including patients and caregivers, to establish goals for the clinic. We created a clinic eligibility criteria and diuretic dosing algorithms based on CARRESS-HF trial and other published studies. We worked with clinic staff to develop a workflow and schedule. We partnered with multidisciplinary providers to enable access to ancillary services while patients received care in clinic. Finally, we met with providers and groups within our hospital and referral institutions to advertise the clinic ( Figure 1 ). Results: Since opening in January 2021, the clinic has had 39 appointments and treated 25 individual patients (min. 1 visit/pt, max. 6 visits/pt). The average patient was 68 years old, with an ejection fraction of 47%. In 85% of visits, the patient was NYHA III-IV. Sixty-eight percent reported that HF had limited their life “quite a lot” or “extremely.” The average patient was 17 lbs. ± 13 lbs. above their dry weight. Ninety-five percent received an IV furosemide bolus and 18% received a subsequent infusion as well. During the visit, 18% saw care management, and 10% saw wound care. The average urine output in clinic was 288cc and the average weight loss within 24-72 hours was 3.6lbs. Conclusions: By engaging local stakeholders and partnering with other providers, administering safe and effective outpatient IV diuresis and multidisciplinary care in a rural setting is possible. More work is needed to determine the impact of nurse led, rural IV diuretic clinics on long-term outcomes.
Abstract 10554: One Year Follow-up After Resuscitated Cardiac Arrest Admitted For Emergency Coronary Angiography: A Prospective, Observational Registry
Authors: QUENTIN DELBAERE, Florence Leclercq, Mariama Akodad, BenoÃ®t Lattuca, Guillaume Cayla
Journal: Circulation (2021)

Introduction: Despite improvement of in-hospital survival rate after aborted sudden cardiac death (SCD), cerebral anoxia may have severe neurologic consequences and may impair long term outcome and quality of life of surviving patients. Methods: This prospective, observational and multicentre (Montpellier and Nimes) study included patients &gt; 18 yo admitted in the cathlab for CA after aborted SCD between May 1, 2018 to May 31, 2020. Only patients who were discharged alive from hospital were evaluated. The primary end point was survival without neurological sequelae at one year follow-up defined by Cerebral Performance Category (CPC) of 1 or 2. Secondary end points included global mortality, NYHA functional class, neurologic evaluation at discharge, 3-months and 1 year follow-up using the CPC scale, and quality of life at 1 year using the QOLIBRI (Quality of LIfe after BRain Injury) questionnaire. Results: Among 143 patients included during the study period, 61 (43%) were discharged alive from hospital and 55 (90%) of them completed follow-up at 1 year. Patients were young (59.4 +/- 14.1), mainly male (77%), with few cardiovascular risk factors. Duration of no and low flow period was short (1.9 +/- 2.4 and 16.5 +/- 10.4 minutes respectively). For 93% of the surviving patients, an initial shockable rhythm (n=57) was observed and acute coronary syndrome (ACS) was diagnosed in 75% of them (n=46). At 1 year, survival rate without neurologic sequelae was 87% (n=48). There were few recurrences of rhythm disorder (5%) or ischemic event (4%). Patients with poor outcome were older (p=0.036), have lower body mass index (p=0.013) and a lower initial LVEF (p=0.046). During follow-up, neurological status improved in 37% of patients presenting sequelae at discharge and overall quality of life was globally satisfying for 66% of patients according to the QOLIBRI questionnaire. No death from cardiac cause was reported, and mean LVEF at 1 year was improved (51.5 ± 9.2 vs 47.5 ± 11.5, p &lt; 0.01). Conclusion: Among patients admitted to the cathlab for aborted SCD, mainly related to ACS, less than half of them were alive at discharge. However, their 1-year survival rate without neurological sequelae was high and their overall quality of life was good.