tbuckley/cabot-search huggingface dataset:
Abstract 14103: Impact of Chronic Kidney Disease on the Association of Cardiovascular and Renal Biomarkers With the Presence and Severity of Coronary Artery Disease in Patients With Suspected Coronary Artery Disease: The EXCEED-J Study
Authors: Hiromichi Wada, Tsuyoshi Shinozaki, masahiro suzuki, Satoru Sakagami, Yoichi Ajiro, JUNICHI FUNADA, Morihiro Matsuda, masatoshi shimizu, Takashi Takenaka, Yukiko Morita, Kazuya Yonezawa, Hiromi Matsubara, Yujiro Ono, Toshihiro Nakamura, Kazuteru Fujimoto, Kazuro Yoshida, Toru Kato, Takashi Unoki, Daisuke Takagi, Moritake Iguchi, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2020)

Background: The impact of chronic kidney disease (CKD) on the association of cardiovascular (CV) and renal biomarkers with the presence and severity of coronary artery disease (CAD) in patients with suspected CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 2324 patients with suspected but no history of CAD undergoing elective coronary angiography, we assessed the impact of CKD on the association of CV and renal biomarkers with the presence and severity of CAD. Heparin-free fasting serum levels of soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), VEGF, placental growth factor (PlGF), N-terminal pro-brain natriuretic peptide (NT-proBNP), contemporary sensitive cardiac troponin-I (cTnI), high-sensitivity CRP (hs-CRP), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured in 887 CKD and 1437 non-CKD patients enrolled in the EXCEED-J study. The severity of CAD was quantified using the Gensini score. Results: The mean age (standard deviation) of the patients was 69.8 (10.8) years; 65.6% were men. Serum levels of all biomarkers except PlGF were significantly higher in CKD than in non-CKD patients. In the entire patient cohort, only natural log-transformed (Ln-) cTnI was significantly associated with CAD, multi-vessel or left main trunk disease (MVD/LMTD), and Ln-Gensini score after adjustment for potential confounders. These associations were still significant in non-CKD, but not in CKD: Ln-cTnI was significantly associated with MVD/LMTD and Ln-Gensini score, but not with CAD. Stepwise regression analyses including potential confounders and all biomarkers revealed that Ln-cTnI was independently associated with CAD, MVD/LMTD, and Ln-Gensini score in the entire cohort and in non-CKD, but not in CKD: Ln-cTnI was independently associated with MVD/LMTD and Ln-Gensini score, but not with CAD. No other biomarker exhibited an independent association with CAD, MVD/LMTD, or Ln-Gensini score in the entire cohort, in non-CKD, or in CKD. Conclusions: Among CV and renal biomarkers measured in this study, only Ln-cTnI was independently associated with the presence and severity of CAD in patients with suspected CAD. These associations were attenuated in patients with CKD.
Abstract 15619: Personalized Assessment of Stroke Risk in AF Patients Undergoing Left Atrial Appendage Closure Using Blood-flow Analysis
Authors: Nikhil Paliwal, Ryan Ohara, Usama A Daimee, Konstantinos Aronis, Rheeda Ali, Tauseef Akhtar, Ronald D Berger, David D Spragg, Hugh G Calkins, Natalia Trayanova
Journal: Circulation (2020)

Introduction: Left atrial appendage (LAA) is the primary source of clot formation that can cause stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF). LAA closure devices have emerged as alternatives to traditional anticoagulation therapy for reducing stroke risk in AF patients. However, ~1-2% of AF patients undergoing LAA closure have subsequent stroke/TIA event. Hypothesis: The presence of a persistent low-flow zone in LA, distinct from LAA, explains why some patients have stroke/TIA events after LAA closure. Methods: We developed a personalized stroke risk prediction tool that uses patient’s CT image to perform computational fluid dynamics simulation and determine presence of low blood-flow in the LA before and after LAA closure. Low flow is quantified by the establishment of low velocity fraction (LVF) in the LA volume, and low wall shear stress fraction (LWSSF) on the surface of the LA wall. The tool was applied retrospectively on 4 AF patients who had undergone LAA closure: 2 patients with TIA 4 months after LAA closure, and 2 controls matched for age, gender, CHA2DS2-VASc score and LAA dimensions with no complications at follow-up up to 2 years. Results: Before LAA closure, TIA and control groups had similar LVF (0.07 and 0.06, respectively) and LWSSF (0.12 and 0.16, respectively). However, after LAA closure, the TIA group had smaller reductions as compared to controls in both LVF (67% vs 79%) and LWSSF (17% vs 52%). This suggests that the LA low-flow region (especially at LA wall) was not substantially reduced after LAA closure, explaining why these patients might have experienced TIA. Conclusion: This proof-of-concept study demonstrates that LAA closure might not substantially reduce low-flow zones for all AF patients, as some retain low-flow zones in LA. Our stroke prediction tool has the potential to identify patients at risk of future stroke/TIA, thus enabling personalized patient selection to increase efficacy of LAA closure devices.
IMPACT OF BASELINE ALANINE AMINOTRANSFERASE LEVELS ON THE SAFETY AND EFFICACY OF REMDESIVIR IN MODERATE COVID-19 PATIENTS
Authors: Gaggar, Anuj, Osinusi, Anu O., Diana M. Brainard
Journal: Hepatology (2020)

Background: Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated potent in vitro and in vivo activity against SAR-CoV-2 and favorable clinical efficacy and tolerability in patients with moderate and severe COVID-19 Elevated transaminase levels are commonly seen in patients with severe COVID-19 prior to treatment Here we report safety and clinical outcomes after RDV treatment in patients with normal versus elevated baseline alanine aminotransferase (ALT) levels Methods: We conducted a randomized, open-label, phase 3 trial, involving hospitalized patients with confirmed COVID-19 pneumonia with Sat 5x the upper limit of normal (ULN) were excluded from the study Patients were randomized 1:1 to receive either 5 or 10 days of intravenous RDV once daily We compared patients with baseline ALT below and above the ULN based on AASLD criteria (ALT 35 U/L for males and 25 U/L for females) Covariates for adjustment included age, sex, race and baseline oxygen support Clinical recovery and all-cause mortality were evaluated using logistic regression Clinical outcomes and adverse events (AEs) were assessed through day 28 Results: Of 397 patients treated with RDV, 215 (54%) had elevated baseline ALT Median ALT was 53 U/L (IQR: 40 - 78 U/L) in the high ALT group Patients with high ALT at time of RDV initiation were younger (median 58 vs 65 years, p<0 001), required less oxygen (p=0 02), and had longer symptom duration (median 10 vs 8 days, p<0 001) prior to first dose of RDV  Incidence of serious AEs, grade ≥3 AEs, and AE leading to discontinuation were similar between groups (Table1)  Grade ≥3 hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher in the high ALT group (8 8% vs 3 3%, p=0 068) Time to clinical recovery, 2-point clinical improvement, 1-point clinical improvement, room air, and death were similar between groups Conclusion: In severe COVID-19 patients, adverse events and clinical outcomes after RDV initiation were similar among patients with baseline normal ALT and those with elevated ALT (1-5x ULN)(Table Presented)
AB0101 Transverse myelitis: a rare manifestation of behÇet’s disease
Authors: C Macieira, C Miranda Rosa, JC Teixeira da Costa, M Viana Queiróz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The diagnosis of Behçet's disease is based on well-known criteria. Although skin, eye and joints are the most frequently involved organs, other systems may be affected such as the nervous system. Transverse myelitis is a rare and serious manifestation of the disease. We present the case of a 51 year-old woman with a 2 year diagnosis of Behçet's disease, initially presented as oral aphtosis, genital ulcerations, symmetrical polyarthritis and a maculo-papular hand rash. Eye examination was normal. The patient remained well for 2 years, when suddenly presented with severe headache, back pain, a rapidly progressive tetraparesia and a global sensitive deficit. Erythrocyte sedimentation rate, C-reactive protein, total blood cell count, lisozyme, angiotensin-converting enzyme and complement factors were within the normal laboratory ranges. The serologic tests for rickettsial and Lyme?s diseases were negative. The immunological study was positive for anti-Scl70 antibody and lupus anticoagulant. Cerebrospinal fluid analysis revealed a 48-cell count with predominance of mononuclear forms and normal cultural and pathology examinations. Spinal cord magnetic resonance imaging (MRI) identified a cervico-thoracic lesion suggestive of transverse myelitis. The cranial MRI was normal. Pulsed methylprednisolone (1 g/day) was initiated, with rapid clinical improvement. After 45 days, with a maintenance dose of prednisone (30 mg/day) the patient was doing well referring residual sensitive deficit. With a one-year follow-up and daily prednisone (20 mg) and azathioprine (50 mg), the patient is assymptomatic and there are no neurological sequelae. A literature review was performed. Central nervous system involvement occurs in less than 5% of cases of Behcet's disease and in this group 69% have clinical manifestations suggestive of transverse myelitis. High methylprednisolone doses are fundamental for favourable clinical outcome. <h3>Objectives &nbsp;Methods &nbsp;Results &nbsp;Conclusion</h3>
Fine-needle aspiration of pancreatic cystic lesions: a randomized study with long-term follow-up comparing standard and flexible needles
Authors: Mohammad Al-Haddad, Michael B. Wallace, William Brugge, Sundeep Lakhtakia, Zhao-Shen Li, Amrita Sethi, Douglas Pleskow, Cuong C. Nguyen, Rahul Pannala, John DeWitt, Massimo Raimondo, Timothy A. Woodward, Mohan J. Ramchandani, Zhendong Jin, Can Xu, Douglas O. Faigel
Journal: Endoscopy (2020)

Pancreatic cystic lesions (PCLs) are increasingly found on cross-sectional imaging, with the majority having a low risk for malignancy. The added value of fine-needle aspiration (FNA) in risk stratification remains unclear. We evaluated the impact of three FNA needles on diagnostic accuracy, clinical management, and the ability to accrue fluid for tumor markers.A multicenter prospective trial randomized 250 patients with PCLs ≥ 13 mm 2:1:1 to 19G Flex, 19G, and 22G needles with crossover for repeated FNA procedures. Diagnostic accuracy was established at 2-year follow-up, with the final diagnosis from surgical histopathology or consensus diagnosis by experts based sequentially on clinical presentation, imaging, and aspirate analysis in blinded review.Enrolled patients (36 % symptomatic) had PCLs in the head (44 %), body (28 %), and tail (26 %). Percentage of cyst volume aspirated was 78 % (72 % - 84 %) for 19G Flex, 74 % (64 % - 84 %) for 22G, and 73 % (63 % - 83 %) for 19G (P = 0.84). Successful FNA was significantly higher for 19G Flex (89 % [82 % - 94 %]) and 22G (82 % [70 % - 90 %]) compared with 19G (75 % [63 % - 85 %]) (P = 0.02). Repeated FNA was required more frequently in head/uncinate lesions than in body and tail (P < 0.01). Diagnostic accuracy of the cyst aspirate was 84 % (73 % - 91 %) against histopathology at 2-year follow-up (n = 79), and 77 % (70 % - 83 %) against consensus diagnosis among nonsurgical cases (n = 171). Related serious adverse events occurred in 1.2 % (0.2 % - 3.5 %) of patients.Our study results demonstrate a statistically significant difference among the three needles in the overall success rate for aspiration, but not in the percentage of cyst volume aspirated. Flexible needles may be particularly valuable in sampling cystic PCLs in the pancreatic head/uncinate process.
Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)
Authors: Michael J Wagner, Megan Othus, Sandip P Patel, Chris Ryan, Ashish Sangal, Benjamin Powers, G Thomas Budd, Adrienne I Victor, Chung-Tsen Hsueh, Rashmi Chugh, Suresh Nair, Kirsten M Leu, Mark Agulnik, Elad Sharon, Edward Mayerson, Melissa Plets, Charles Blanke, Howard Streicher, Young Kwang Chae, Razelle Kurzrock
Journal: Journal for ImmunoTherapy of Cancer (2021)

Purpose Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study. Methods This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used. Results Overall, there were 16 evaluable patients. Median age was 68 years (range, 25–81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3–4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR. Conclusion The combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma. Trial registration number NCT02834013 .
Abstract 13747: Investigation of the Probability of Spontaneous Conversion From Atrial Fibrillation to Sinus Rhythm Utilizing Continuous Rhythm Monitoring
Authors: Paul D Ziegler, Efstratios I Charitos
Journal: Circulation (2020)

Introduction: Atrial fibrillation (AF) recurrence or spontaneous conversion to sinus rhythm (SR) are regarded as random events. Hypothesis: We hypothesized that the probability of spontaneous conversion to SR decreases as more time is spent in AF. We attempt to quantify this phenomenon and investigate factors that can affect this probability. Methods: Cardiac rhythm histories of 1195 patients (age 73.0 ± 10.1, follow-up: 349 ± 40 days; 14533 AF episodes) with implantable devices were reconstructed and analyzed. No patients received cardioversion, AF ablation, or any obvious AF therapies during follow-up. Patients with no AF recurrence or continuous AF during follow up were excluded. Hierarchical regression methods were employed to investigate the time course of the probability of rhythm change and factors that influence it. Results: Probabilities of spontaneous conversion from AF to SR (solid blue line) and recurrence of AF in patients with SR (solid red line) are shown in the Figure. For patients in AF , spontaneous conversion probability significantly decreases with time spent in AF and plateaus after ~7 days (dotted blue line). Similarly for patients in SR, increasing time in SR reduces the probability of developing AF (solid red line) and plateaus after ~7 days (dotted red line). Patient age (p&lt;0.001), LVEF (p&lt;0.05) and presence of coronary artery disease (p&lt;0.01) significantly influence the spontaneous conversion probabilities independent from AF burden. Conclusions: Spontaneous SR conversion or AF recurrence diminishes with increasing time spent in AF or SR, respectively, and are influenced by several patient-related factors. These findings suggest that patients should be closely monitored after AF recurrence or SR conversion.
ETNK1 Mutations in Atypical Chronic Myeloid Leukemia Induce a Mutator Phenotype That Can be Reverted with Phosphoethanolamine
Authors: Diletta Fontana, Mario Mauri, Rossella Renso, Mattia Docci, Ilaria Crespiatico, Lisa M Røst, Mi Jang, Antonio Niro, Deborah D'Aliberti, Luca Massimino, Mayla Bertagna, Giovanni Zambrotta, Mario Bossi, Stefania Citterio, Barbara Crescenzi, Francesca Fanelli, Valeria Cassina, Roberta Corti, Domenico Salerno, Luca Nardo, Clizia Chinello, Francesco Mantegazza, Cristina Mecucci, Fulvio Magni, Guido Cavaletti, Per Bruheim, Delphine Rea, Steen Larsen, Rocco Piazza, Carlo Gambacorti-Passerini
Journal: Blood (2020)
Abstract 17183: Severity of Myocardial Injury in COVID-19 Hospitalized Patients
Authors: Saagar K Sanghvi, Logan Schwarzman, Noreen Nazir, Sreenivas Konda
Journal: Circulation (2020)

Introduction: Myocardial injury in COVID19 is reported as high as 30% and associated with worsened prognosis (Cooper et al., Circulation). Along with elevated cardiac biomarkers, elevated inflammatory markers of cytokine storm and hemophagocytic lymphohistiocytosis (HLH) are associated with increased illness severity and mortality. Our study aimed to identify patients at highest risk for myocardial injury and subsequent cardiac decompensation. Methods: 279 consecutive patients with COVID19 from a major metropolitan academic center, discharged from 3-21-2020 to 5-17-2020, were analyzed. Primary data includes age, sex, race, and peak troponin I during hospitalization. Patients were further stratified to evaluate severe cases with acute respiratory distress syndrome (ARDS) requiring intubation (n=40), and peak levels of CRP, ferritin, and D-dimer were collected. Bivariate and multivariate measures of association between peak inflammatory marker and troponin I levels were estimated. Results: Average age of ARDS population patients was 61 +/- 15 years; 50% male and 50% female. Self-identified African Americans(AA) were 35%, Hispanic/Latinos(H/L) were 55%, and Others including two White Americans were 10%. Average peak troponin I in H/L was remarkably higher 0.51 +/-1.16 compared to AA 0.18 +/- 0.23 and Others 0.13 +/- 0.16. Per multivariate regression analysis, D-dimer had the most significant effect on the elevated troponin (p=0.027). Although weakly significant, H/L showed elevated troponin (p =0.09) compared to non-H/L. Conclusion: Elevated D-dimer is associated with increased morbidity in COVID19, and also correlates with elevated troponin concerning for increased myocardial injury. Furthermore, the H/L population may be at greater risk for developing myocardial injury and have more injury as shown by higher troponin I levels. Larger studies may better assess the relation between inflammatory markers such as CRP and ferritin and myocardial injury. Our study provides evidence of systemic inflammation contributing to significant myocardial injury in COVID19, especially in the H/L population. Identifying patients at highest risk for myocardial injury early may allow for more effective medical interventions and improved outcomes.
THU0232 Fas and apoptosis in patients with familial mediterranean fever and amyloidosis
Authors: S Kiraz, I Ertenli, M Çalgüneri, MA Oztürk, E Atalar, S Apras, IC Haznedaroglu, S Kirazlı
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Amyloidosis is the drastic complication of familial Mediterranean Fever (FMF). Amyloidosis may be characterised by a tendency for keratinocytes to undergo filamentous degeneration and apoptosis. However, a possible association of FMF and apoptosis has not been previously evaluated. Binding of Fas ligand (FasL) to the Fas antigen trigger the cytoplasmic apoptotic signal. Induced cell death can be inhibited by soluble Fas protein (sFas) which binds to and functions as competitive antagonist of FasL. <h3>Objectives</h3> The aim of this study was to investigate sFas in patients with FMF complicated with amyloidosis compared to FMF patients without amyloidosis and controls. <h3>Methods</h3> Ten FMF patients with amyloidosis (mean age: 41.8, min-max: 33–51), 12 patients with FMF without amyloidosis (mean age: 24.8, min-max: 17–38) and 16 controls (mean age: 48.7, min-max: 38–63) were enrolled in the study. All FMF patients were in attack-free period during blood sampling. sFas levels were measured using a commercially available ELISA kit (Quantikine sFas Immunoassay). <h3>Results</h3> <h3>Conclusion</h3> Decreased serum sFas levels may lead to unbalanced binding of FasL to its receptor, inducing apoptosis. <i>In vitro</i> experiments demonstrated that long-term enhancement of Fas expression in Fas-normal mice resulted in an increased acute-phase response and renal amyloidosis in aged transgenic mice. Increased Fas expression in T cells of aged CD2-Fas transgenic CD-1 mice resulted in an increased immune response and T cell apoptosis. Therefore, enhanced Fas-mediated apoptosis can be associated with amyloidosis in FMF patients, and this association may be related to the dysregulated immune system activation. On the other hand, elevated levels of sFas protein in patients with FMF may also be related to the imbalanced inflammatory activity. Induced cell death of autoreactive T cells could be inhibited by sFas. sFas levels were shown to be elevated in patients with active SLE. However this observation could not be confirmed by some other authors. Since the changes in autoimmune inflammatory disorders are dynamic and complex, it is difficult to establish a relationship between sFas and their pathogenesis. It also remains to be detected which cells release the elevated amounts of sFas. Future studies are needed to elucidate exact state of sFas protein in the etiopathogenesis of FMF.