tbuckley/cabot-search huggingface dataset:
Use of Cardiac Resynchronization Therapy Defibrillator in US Hospitals
Authors: Amneet Sandhu, Haikun Bao, Karl E. Minges, Paul D. Varosy, Ryan T. Borne, Mathew M. Zipse, Lucas Marzec, Pamela Peterson, Frederick Masoudi, Steven M. Bradley
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Cardiac resynchronization therapy (CRT) provides significant reduction in morbidity and mortality in select patients with left ventricular systolic dysfunction and specific parameters of electrocardiographic evidence of dyssynchrony. Relative to the 2012 American College of Cardiology/American Heart Association/Heart Rhythm Society guideline update for patient selection, little is known about the contemporary use of CRT in the United States. <h3>Objective</h3> To describe the use of CRT defibrillator (CRT-D) in the period around guideline revision. <h3>Design, Setting, and Participants</h3> All patients undergoing new CRT-D implantations in the National Cardiovascular Data Registry for implantable cardioverter-defibrillators from January 1, 2012, to December 31, 2015, at 1710 participating hospitals were identified for this population-based study. Rates of CRT-D implantation that were concordant and discordant with the 2012 American College of Cardiology/American Heart Association/Heart Rhythm Society update of the 2008 guidelines for device-based therapy were determined. Analysis began in January 2012. <h3>Main Outcomes and Measures</h3> Increase in guideline-concordant CRT-D implantation. <h3>Results</h3> Among 135 253 patients undergoing initial CRT-D implantation, 88 923 were included in the study cohort, of which 73 859 implants (83.1%) were guideline concordant. The proportion of guideline-concordant devices increased from 81.2% (16 710 of 20 481) in 2012 to 84.2% (20 515 of 24 356) in 2015 (<i>P</i>for trend &lt; .001). Significant clustering was noted with 33% (565 of 1710) of hospitals accounting for greater than 70% (10 545 of 15 065) of guideline-discordant CRT-D implants. Conduction abnormalities, in particular, underlying right bundle branch block (3597 [23.9%] vs 7425 [10.1%];<i>P</i> &lt; .001) and nonspecific intraventricular conduction delay (3341 [22.2%] vs 4769 [6.5%];<i>P</i> &lt; .001) were more common in those who received guideline-discordant devices. <h3>Conclusions and Relevance</h3> Rates of guideline-concordant CRT-D implantation increased during the study. The major fraction of guideline-discordant implants were clustered at a minority of hospitals. Conduction abnormalities, particularly non–left bundle branch block and nonspecific intraventricular conduction delay, correlated with guideline-discordant implants indicating continued opportunity for dissemination and understanding of guideline updates.
Identification of preexisting adaptive immunity to Cas9 proteins in humans
Authors: Carsten T. Charlesworth, Priyanka S. Deshpande, Daniel P. Dever, Joab Camarena, Viktor T. Lemgart, M. Kyle Cromer, Christopher A. Vakulskas, Michael A. Collingwood, Liyang Zhang, Nicole M. Bode, Mark A. Behlke, Beruh Dejene, Brandon Cieniewicz, Rosa Romano, Benjamin J. Lesch, Natalia Gomez-Ospina, Sruthi Mantri, Mara Pavel-Dinu, Kenneth I. Weinberg, Matthew H. Porteus
Journal: Nature Medicine (2019)
PB1838 EPISTAXIS IN PEDIATRIC TERTIARY OUT‐PATIENT CLINIC: COULD IT BE AN ALARMING SIGN?
Authors: M. Elalfy, A. Tantawy, B.E. Badr Eldin, F. Ebeid, M.A. Mekawy, Y. Mohammad
Journal: HemaSphere (2019)

Background: Epistaxis could be an alarming bell to diagnose a hemostatic disorder. Aims: To detect those with possible bleeding tendencies using simple tools of assessment. Methods: A prospective study for children attended tertiary pediatric out‐patient clinic (POPC) over a one year; who had been presented with epistaxis of non‐apparent cause. They underwent clinical assessment and parents answered pediatric bleeding questionnaire and epistaxis severity score. Complete blood count and coagulation profile, platelet function screening tests. Results: 100 patients less than 18 years with epistaxis (53 females and 47 males), estimated annual frequency of epistaxis was 1 in 300 children attended Ain Shams University out‐patient clinic. Half of them were younger than six years. 76 had recurrent epistaxis and 12 had systemic comorbidities. 90% presented by anterior nasal bleeding and the majority had been controlled just by nasal compression. 43 patients presented with epistaxis only; 15% had definite local cause, 85% of them were considered idiopathic on initial evaluation. 57 presented with other bleeding manifestations; 82% of them had a definite hemostatic disorder and ten percent needed further assessment. There was a positive family history for epistaxis in half of those with definite hemostatic disorders. A bleeding score of ≥2 showed significant value in suspecting hereditary hemostatic disorder as a cause of epistaxis. Summary/Conclusion: Epistaxis as a presenting symptom to the POPC is not uncommon; the use of pediatric bleeding questionnaire was helpful to detect those with an underlying hemostatic disorder. Epistaxis was a presenting symptom for a hemostatic bleeding disorder in half of the referred cases. Still around 20% of epistaxis with suspected hemostatic disorder need further studies to reach a definite diagnosis.
Abstract 13076: Lipid-lowering Therapy Stabilizes the Complexity of Non-culprit Plaques in Human Coronary Artery: A Quantitative Assessment Using OCT Bright Spot Algorithm
Authors: Yoshiyasu Minami, Taylor Hoyt, Jennifer E Phipps, Thomas E Milner, Lei Xing, Bo Yu, Marc D Feldman, Ik-Kyung Jang
Journal: Circulation (2015)

Introduction: Recent studies using optical coherence tomography (OCT) reported that statin therapy increases the thickness of fibrous cap in human coronary plaques. However, the efficacy on the stabilization of plaque complexity remains unknown. Aim: To quantitatively evaluate the statin efficacy on the change of plaque complexity using an OCT bright spot algorithm. Methods: From a randomized trial (NCT01023607), we identified 59 lipid-rich coronary plaques in non-culprit lesions from 40 patients who were randomized to receive atorvastatin 60mg (AT60), rosuvastatin 10mg (RT10) or atorvastatin 20mg (AT20), and had serial image acquisition at baseline, 6-month, and 12-month by time-domain OCT. We applied an OCT algorithm which is able to identify bright spots representing variety of plaque components including macrophage. The density of bright spots was measured within superficial 250μm of the vessel wall as the number of bright pixels divided by the number of pixels in each frame through the entire plaque length. Results: Significant reduction of bright spot density was observed from baseline to 12-month, particularly during the second 6 months (Figure). All three types of statin demonstrated the marked reduction of bright spot density from the baseline to 12-month (-0.61% [-0.93, -0.34], P&lt;0.001, -0.45% [-0.99, -0.34], P=0.001 and -0.41% [-0.98, -0.19], P&lt;0.001, in AT60 (n=22), RT10 (n=15) and AT20 (n=22), respectively) without significant difference among the groups (P=0.76). There was no significant difference in the reduction of bright spot density from baseline to 12-month between patients with acute coronary syndrome (n=47) and those with stable angina (n=12) (-0.49% [-0.97, -0.28] vs. -0.41% [-0.89, -0.21], P=0.62). Conclusions: Coronary plaque complexity evaluated by a quantitative OCT algorithm was significantly improved by 12-month statin therapy irrespective of the statin type and baseline clinical presentation.
Abstract 3351: Erectile Dysfunction Predicts Peripheral Arterial Disease as Measured by Screening Ankle Brachial Index Testing
Authors: R Parker Ward, Justin Weiner, S Nasir Ghani, Linda A Taillon, James K Min
Journal: Circulation (2006)

Background: Peripheral arterial disease (PAD) as determined by ankle brachial index (ABI) testing is a potent marker of adverse cardiovascular prognosis, yet PAD frequently remains asymtomatic or u...
A Tribute to John Mendelsohn: A Pioneer in Targeted Cancer Therapy
Authors: Rakesh Kumar, Marc Van de Vijver, Giampaolo Tortora, Fortunato Ciardiello, Tzipora Goldkorn, Wilson H. Miller, Larry Norton
Journal: Cancer Research (2019)

Cancer scientists and clinicians are mourning the death of one of the most accomplished members of their community: Dr. John Mendelsohn. He was a pioneer in targeted cancer therapy and was instrumental for the discovery and deployment of the first antagonist epidermal growth factor receptor (EGFR) therapeutic antibodies, broadening the concept of targeted EGFR therapy to encompass other receptor tyrosine kinases, such as HER2, and developing blocking antibody-combination therapy with chemotherapies or radiotherapy. Dr. Mendelsohn, who died on January 7, 2019, always led by the strength of his accomplishments and the humility of his character. Above all, he was a well-revered mentor and clinician, who extended compassion and the gift of his time to patients, colleagues, and mentees alike. In tribute to Dr. Mendelsohn, Cancer Research has invited his former mentees and colleagues who were associated with Dr. Mendelsohn for over three decades to reflect on the broad impact of his work. Here, we discuss Dr. Mendelsohn's illustrious career at three elite academic cancer institutions and hospitals in the United States, his acumen to build, grow, and uplift institutions, and train a generation of medical oncologists, physician scientists, and cancer biologists. His profound legacy on targeted therapy and cancer research and treatment continue to prolong and save the lives of cancer patients globally.
Tumor-associated macrophage expression of interferon regulatory Factor-8 (IRF8) is a predictor of progression and patient survival in renal cell carcinoma
Authors: Jason B. Muhitch, Nicholas C. Hoffend, Gissou Azabdaftari, Austin Miller, Wiam Bshara, Carl D. Morrison, Thomas Schwaab, Scott I. Abrams
Journal: Journal for ImmunoTherapy of Cancer (2019)

Tumor-associated macrophages have been well-characterized in solid malignancies, including renal cell carcinoma and generally correlate with poor prognosis. However, the molecular mechanisms which govern intratumoral macrophage behavior and patient outcome are unclear. Here, we investigated whether alterations in macrophage expression of the transcriptional regulator for myeloid commitment and function, interferon regulatory factor-8 (IRF8), could predict survival of clear cell renal cell carcinoma patients. Transcriptional analysis of publicly available data revealed elevated IRF8 expression was associated with prolonged disease-free survival. Evaluation of protein expression within histologic sections of primary clear cell renal cell carcinoma patient samples showed intensity of IRF8 by CD68
PB1773 OVERAL SURVIVAL OF MEXICAN NATIONAL REGISTRY OF ACUTE PROMYEOLOCYTIC LEUKEMIA, AN ANALYSIS OF 324 CASES
Authors: N. Zapata, E. Montaño, C. Ramos, R. Espinoza, J.C. Solis, E. Barrera, J. Mijangos, G. Diaz, R. Solís, O. Perez, M. Herrera, D. Gomez, A. Cabrera, J.A. Flores, M. Solano, V. Guillermo, A. Ceballos, J. Ojeda, G. Gomez, L. Lyn, V. Mena, J.A. De la Peña, M. Ortiz, J. Perez, M.E. Espitia, J.L. Alvarez, M. Aguilar, M. Alvarado
Journal: HemaSphere (2019)

Background: Acute Promyelocytic Leukemia is a myeloid dissease wich is informed to be more frequent in latinos, but there is few epidemiological data about these. This is a review of 19 Hospitals in different states of Mexico, from Northern to South of Mexico. A retrospective study of all cases of acute promyelocytic leukemia treated from 2007‐2018, a total of 324 cases. Aims: Our Aim objective is to know our overall survival of the population with acute promyelocyic leukemia treated in different institutions in Mexico Secondary objectives: Learn about treatment used in theses different institutions, and mortality related. Methods: We perform a rtrospective analysis from 2007‐2018, a total of 324 cases diagnose with acute promylocytic leukemia, inform consent was perform in all cases Results: The Median age 36 years old (range 15‐73), relation male:female 163:161. Infection at diagnosis 12%(39cases), DIC 31% (102 cases), Hemorrages 21%, CNS:8cases, Gastrointestinal 18cases, urinary tract:15, skin:28 cases. Leucocite at diagnosis median of 22.3 (1.0‐450), Platelets median of 40 (2‐318), Fybrogen median 190 range22‐825, TTPa 32 seconds (28‐255). Risk at diagnosis: low 36%, intermediate:24%, high risk:40%. ATRA used in 94% of the cases and antracyclines used Daunorrubicin 58%, and Idarrubicin 42%. Mortality of 14%. ATRA syndrome 16% in the Daunorrubicin arm and 20% idarrubicin Summary/Conclusion: We show that patient treated with daunorrubicin had a better survival during the induction, with a overall mortality of 14% in the induction related mortality. Median age of diagnosis 36 years old. In Mexico there is no ATO, so we still treating patients with chemotherapy and a maintenance of 2 years afther 3 consolidations, the most used atracycline is daunorrubicin. There was no difference between the ATRA syndrome in both antracyclines.
18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma
Authors: Trond V. Bogsrud, Ayca Londalen, Petter Brandal, Henning Leske, Ioannis Panagopoulos, Per Borghammer, Tore Bach-Gansmo
Journal: Clinical Nuclear Medicine (2019)

Purpose To retrospectively investigate the uptake of 18 F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG). Methods Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth. Results All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1–20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to &gt;400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1–84.4). In 4 patients, 18 F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR. Conclusions The uptake of 18 F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of 18 F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.
Abstract #494: Anti-inflammatory effects of the nigella sativa seed extract, thymoquinone, in pancreatic cancer cells
Authors: Navdeep Chehl, Galina Chipitsyna, Qioake Gong, Charles Yeo, Hwyda Arafat
Journal: Cancer Research (2009)

Background: Both hereditary and sporadic forms of chronic pancreatitis are associated with an increased risk of developing pancreatic ductal adenocarcinoma (PDA). Inflammation has been identified as a significant factor in the development of solid tumor malignancies. Thymoquinone (Tq), the major constituent of the Nigella sativa oil extract induces apoptosis and inhibits PDA cell proliferation. Tq also increases p21 WAF1 expression, inhibits histone deacetylase (HDAC) activity, and induces histone hyperacetylation. HDAC inhibitors have been shown to ameliorate inflammation-associated cancer in several animal models. Objective: To evaluate the anti-inflammatory potential of Tq in PDA cells in comparison to a specific HDAC inhibitor, trichostatin A (TSA). Methods: PDA cells (AsPC-1, HS766T, MiaPaca) were cultured and treated with or without Tq (25-75 \#956;M), with or without pre-treatment of TNF-\#945; (30nM). The effect of Tq on the expression of different proinflammatory cytokines and chemokines was analyzed by real time PCR. Luciferase-labeled promoter studies evaluated the effect of Tq on the transcription of monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-\#954;B (NF-\#954;B). The effect of Tq on the endogenous and TNF-\#945;-induced activation and nuclear translocation of NF-\#954;B was examined by ELISA and immunohistochemistry. Results: Within 6 h, Tq significantly and dose-dependently reduced PDA cell production of TNF-\#945; (p  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 494.
IRF-1 mediates apoptosis and FADD/activated caspase 8 complex formation in breast carcinoma independent of the death ligands Fas, TNFa and TRAIL
Authors: Michael T. Stang, Michaele J. Armstrong, Greg Watson, Ye Liu, Ki-Young Sung, John H. Yim
Journal: Cancer Research (2006)

766  Background Interferon regulatory factor 1 (IRF-1) is a nuclear transcription factor with known tumor suppressor activity and has been shown to induce apoptosis in breast cancer. The mechanism of IRF-1 mediated apoptosis is largely unknown. We hypothesize that IRF-1 induces apoptosis through a caspase 8 mediated death pathway. Methods MDA-MB-468 breast cancer cells were transfected with recombinant adenovirus (Ad-Null or Ad-IRF-1) at an MOI of 25 caspase 8 specific inhibitor IETD (50 uM). Whole cell lysates at 24 hours underwent immunoblotting for caspases 8, 3 and 7. Immunoprecipation was performed at 24 hours (Ad-Null or Ad-IRF-1) with anti-FADD antibody and analyzed by immunoblotting for caspase 8. Cells treated with recombinant TRAIL, FasL and TNFa (100 ng/mL) were analyzed at 24 hours for apoptosis by Annexin V/PI flow cytometry. Transduced cells (Ad-Null and Ad-IRF1) blocking antibodies to TNFR, Fas and TRAIL receptors DR4/DR5 (20 ug/mL) were analyzed at 24 hours for apoptosis by flow cytometry. Results IRF-1 induces marked apoptosis compared to control (Ad-Null 6.4% Annexin V positive, Ad-IRF-1 33.7%) and induces caspase 8 cleavage followed by cleavage of both caspase 3 and 7 which is blocked by a caspase 8 specific inhibitor. Immunoprecipitation of FADD in IRF-1 transduced cells shows formation of a FADD and activated caspase 8 complex. TRAIL, FasL and TNFa alone do not induce apoptosis nor caspase 8 cleavage/activation in MDA-MB-468 breast cancer cells. Blocking antibodies to TNFR, Fas or TRAIL receptors do not inhibit IRF-1 induced apoptosis (Ad-IRF-1 plus TNFR Ab 40.7% Annexin V positive, Ad-IRF-1 plus Fas Ab 33.7%, Ad-IRF-1 plus DR4 Ab 48.5%, Ad-IRF-1 plus DR5 Ab 43.6%). Conclusions IRF-1 induces apoptosis and is accompanied by caspase 8 cleavage and formation of a FADD and activated caspase 8 complex in human MDA-MB-468 breast cancer cells. This appears to be independent of the death ligands FasL, TRAIL and TNFa. Targeting of IRF-1 expression may provide insight into a mechanism of cell death mediated by FADD and caspase 8 independent of death ligands.
PF780 STEM CELL TRANSPLANTATION FOR ACQUIRED APLASTIC ANEMIA: THE ROLE OF THE CONDITIONING REGIMEN
Authors: S. Giammarco, M.T. Van Lint, R. ONETO, C. Di Grazia, A.M. Raiola, S. Bregante, T. Lamparelli, F. Gualandi, R. Varaldo, S. Sica, E. Angelucci, A. Bacigalupo
Journal: HemaSphere (2019)

Background: Hemopoietic stem cell transplantation (HSCT) remains the standard of care for eligible patients with acquired aplastic anemia (AA). Conditioning rfegimens have changed over the years Aims: To asses the role of different conditioning regimens over the years in HSCT in patients with acquired AA Methods: We have analyzed the outcome of 179 patients with acquired aplastic anemia (AA) undergoing an HSCT in 3 consecutive eras: before year 2000, between 2001 and 2010 and beyond year 2010. The median age of the patients was 20,28,31 years in the three periods, and there has been an increased use of donors other than HLA identical siblings (6%, 45%, 62% respectively). The major change in the 3 periods, has been in the use of conditioning regimens: cyclophosphamide (CY) 200 mg/kg was used in 92%, 32% and 20% of patients respectively in the 3 periods; the combination of fludarabine (FLU), CY low dose (1200 mg/m^2) and total body irradiation 2 Gy (FLU‐LDCY‐TBI) was used in 5%, 58% and 20% of patients in the 3 periods; finally the combination of FLU CY 120 mg/kg and TBI 2 Gy (FLU‐CY‐TBI) was given to 0%, 9%, 58% of patients respectively. GvHD prophylaxis remained unchanged during the three transplant periods: cyclosporin methotrexate and ATG for all patients, with the addition of rituximab 200 mg on day+5, as of year 2002. Results: The 5 year survival has improved in three consecutive transplant eras, from 58% before year 2000, to 73% in the years 2001–2010, and 92% in the years 2011–2018.We then compared the outcome of transplants prepared with FLU‐LDCY‐TBI (n = 38) or with FLU‐CY‐TBI (n = 21): the 2 groups were comparable for patients age (31 years for FLU‐LDCY‐TBI, range 17–60, versus 39 years for FLU‐CY‐TBI, range 18–62, p = 0.2) and donor type (p = 0.2), with 44% and 55% of donors being unrelated. The 5 year survival was 62% for FLU‐LDCY‐TBI vs 95% for FLU‐CY‐TBI (p = 0.02). In the FLU‐LDCY‐TBI, 4 patients died of graft failure (11%), 7 died of infections (18%) and 3 (8%) of toxicity. In the FLU‐CY‐TBI, 1 patient died of rejection (4%) and 1 of GvHD (4%). No patient experience EBV‐driven post transplant lymphoproliferative disorders (PTLD) Summary/Conclusion: In conclusion CY200 mg/kg remains standard of care for young patients grafted from identical siblings. The combination of FLU‐CY 120 mg/kg and TBI2 Gy appears to allow a better engraftment as compared to FLU‐LDCY‐TBI, and may be preferred for older patients and patients grafted from unrelated donors. We recommend low dose rituximab on day+5, which will effectively prevent PTLD.