tbuckley/cabot-search huggingface dataset:
Aggressive Bone Metastatic Prostate Cancer With Periosteal Reaction in 18F-Choline PET/CT
Authors: Nicolas De Leiris, Valentin Ruggeri, Laurent Riou, Mathieu Laramas, Loïc Djaileb
Journal: Clinical Nuclear Medicine (2020)

Abstract Prostate cancer bone metastases usually appear as osteosclerotic lesions. However, atypical lesions have also been described. We report herein the case of a 65-year-old man treated since 2013 for prostate cancer with early bone metastases. This asymptomatic patient was referred for 18 F-choline PET/CT due to a major elevation of prostate-specific antigen to &gt;1500 ng/mL. The results indicated multiple bone lesions, disseminated on the axial skeleton, girdles, and upper extremities of femurs. Interestingly, we described the development of an intensely hypermetabolic spiculated periosteal reaction, evidencing a rapidly progressive disease.
Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction
Authors: Sean P. Murphy, Margaret F. Prescott, Alexander Camacho, Seethalakshmi R. Iyer, Alan S. Maisel, G. Michael Felker, Javed Butler, Ileana L. Piña, Nasrien E. Ibrahim, Cheryl Abbas, John C. Burnett, Scott D. Solomon, James L. Januzzi
Journal: JACC Heart Failure (2020)

This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP.In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment.Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both).Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).
Abstract 16489: Comparison of Severity of Illness at Presentation and Outcomes for Patients With Acute Cardiovascular Syndromes Before and During Covid-19 Pandemic
Authors: Cristina Sanina, Mohamed Gabr, Luigi DiBiase, Jose M Wiley, Mario J Garcia
Journal: Circulation (2020)

Introduction: The New York Governor Andrew M. Cuomo’s executive order N202.25 on March 7, 2020, canceled all elective, semi-urgent procedures, including cardiovascular interventions such as coronary angiography and angioplasty due to SARS- Cov2 (COVID 19) pandemic. New York City was devastated by COVID 19 infection carrying the highest incidence, prevalence, and mortality rates in the US. Importantly, a 4. 4.83-fold increase in death rate at home was reported. We hypothesized that the COVID19 surge postponed the patient's decision to seek medical attention leading to an increase in cardiovascular-related hospital mortality. Methods: We conducted a retrospective observational study examining the incidence, prevalence, complication rate, and mortality from cardiovascular diseases in hospitalized patients during COVID 19 surge. We performed a patient chart review of a cohort with acute cardiovascular events (STEMI, NSTEMI, Stroke, CHF) during the COVID 19 surge who were hospitalized at Montefiore Medical Center between March 7, 2020, and April 21, 2020, and compared it to a similar cohort from the preceding year (March 7, 2019 and April 21, 2019). Results: During the dates (March 7- April 21, 2020), there was a significant decrease in NSTEMI, stroke, and CHF admissions (P&lt;0.05). (Figure 1) Respectively, fewer cardiac catheterization procedures were performed for patients presenting with NSTEMI, UA, and shock. There was no difference in the number of STEMI admissions. Troponin T levels at presentation were significantly higher (P&lt;0.05), and increased prevalence of wall motion abnormalities and LVEF &lt; 50% (P&lt;0.05). Mortality for HF asdmissions was 20% in 2020 compared to 0.02% in 2019. Conclusions: Montefiore Medical Center admitted and treated significantly fewer patients with acute cardiovascular syndromes during the COVID19 surge. Non-COVID patients presented with delayed MI. All HF patients (COVID+Non-COVID) carried a significantly higher mortality rate.
Abstract 13830: Soluble Klotho Suppresses Human Aortic Valve Interstitial Cell Fibrocalcification Induced by Fibroblast Growth Factor 23
Authors: Erlinda The, Lihua Ao, Yufeng Zhai, David A Fullerton, Xianzhong Meng
Journal: Circulation (2020)

Aortic valve interstitial cells (AVIC) play a major role in the pathogenesis of calcific aortic valve disease (CAVD). Higher fibroblast growth factor 23 (FGF23) levels are associated with chronic kidney disease (CKD), an important risk factor of CAVD. The role of FGF23 in AVIC pathobiology associated with CAVD remains unclear. Klotho (KL) is an anti-aging protein present in membrane (mKL) and soluble (sKL) forms. While mKL is a coreceptor for FGF23, sKL may function as a FGF23 antagonist. We have found that KL inhibits osteogenic activity in AVIC exposed to CKD-associated high phosphate condition. We hypothesized that FGF23 mediates AVIC fibrocalcification, and sKL inhibits the effect of FGF23. Methods and Results: Protein levels of FGF23 and KL were analyzed in AVIC and aortic valves from CAVD patients. Diseased aortic valves and AVIC had higher FGF23 and lower KL levels than normal valves and AVIC, and diseased AVIC secreted greater amount of FGF23. Knockdown or neutralization of FGF23 in diseased AVIC suppressed their spontaneous fibrocalcification. Treatment of normal AVIC with recombinant FGF23 (40 ng/ml) for 72h enhanced the expression of collagens I and IV, Runx2, and alkaline phosphatase. Prolonged treatment of normal AVIC with FGF23 resulted in collagen and calcium deposition. Elevated levels of FGF receptor (FGFR) 1 and 4 were detected in normal AVIC after FGF23 stimulation. Inhibition of FGFR1 attenuated FGF23-induced fibrogenic response, while inhibition of FGFR4 abrogated FGF23-induced osteogenic response. Recombinant KL (0.5 μg/ml) reduced FGFR expression and fibrocalcification induced by FGF23. Further, KL attenuated FGF23-induced collagen and calcium deposition in normal AVIC. In vitro incubation of KL and FGF23 led to the formation of a complex. Conclusion: Diseased aortic valves and AVIC have higher levels of FGF23 and lower levels of KL. FGF23 is capable of inducing fibrocalcification in normal AVIC via FGFR1 and FGFR4. sKL suppresses FGF23 activities by inhibiting FGFR upregulation and direct interaction with FGF23. Our novel findings suggest that FGF23 may accelerate CAVD progression. sKL suppresses the pro-fibrocalcific effect of FGF23 and may offer therapeutic potential for slowing CAVD progression, especially in CKD patients.
Standardized Definitions for Evaluation of Heart Failure Therapies: Scientific Expert Panel From the Heart Failure Collaboratory and Academic Research Consortium
Authors: William T. Abraham, Mitchell A. Psotka, Mona Fiuzat, Gerasimos Filippatos, JoAnn Lindenfeld, Roxana Mehran, Amrut V. Ambardekar, Peter E. Carson, Richard Jacob, James L. Januzzi, Marvin A. Konstam, Mitchell W. Krucoff, Eldrin F. Lewis, Jonathan P. Piccini, Scott D. Solomon, Norman Stockbridge, John R. Teerlink, Ellis F. Unger, Emily P. Zeitler, Stefan D. Anker, Christopher M. O’Connor
Journal: JACC Heart Failure (2020)
Incremental Risk of Developing Severe COVID-19 Among Mexican Patients With Diabetes Attributed to Social and Health Care Access Disadvantages
Authors: Sandra G. Sosa-Rubí, Jacqueline A. Seiglie, Carlos Chivardi, Jennifer Manne-Goehler, James B. Meigs, Deborah J. Wexler, Veronika J. Wirtz, Octavio Gómez-Dantés, Edson Serván-Mori
Journal: Diabetes Care (2020)

OBJECTIVE Diabetes is an important risk factor for severe coronavirus disease 2019 (COVID-19), but little is known about the marginal effect of additional risk factors for severe COVID-19 among individuals with diabetes. We tested the hypothesis that sociodemographic, access to health care, and presentation to care characteristics among individuals with diabetes in Mexico confer an additional risk of hospitalization with COVID-19. RESEARCH DESIGN AND METHODS We conducted a cross-sectional study using public data from the General Directorate of Epidemiology of the Mexican Ministry of Health. We included individuals with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 between 1 March and 31 July 2020. The primary outcome was the predicted probability of hospitalization, inclusive of 8.5% of patients who required intensive care unit admission. RESULTS Among 373,963 adults with COVID-19, 16.1% (95% CI 16.0–16.3) self-reported diabetes. The predicted probability of hospitalization was 38.4% (37.6–39.2) for patients with diabetes only and 42.9% (42.2–43.7) for patients with diabetes and one or more comorbidities (obesity, hypertension, cardiovascular disease, and chronic kidney disease). High municipality-level of social deprivation and low state-level health care resources were associated with a 9.5% (6.3–12.7) and 17.5% (14.5–20.4) increased probability of hospitalization among patients with diabetes, respectively. In age-, sex-, and comorbidity-adjusted models, living in a context of high social vulnerability and low health care resources was associated with the highest predicted probability of hospitalization. CONCLUSIONS Social vulnerability contributes considerably to the probability of hospitalization among individuals with COVID-19 and diabetes with associated comorbidities. These findings can inform mitigation strategies for populations at the highest risk of severe COVID-19.
Abstract 13284: Cardiac Rehabilitation, Cardiorespiratory Fitness, and Risk of Incident Atrial Fibrillation in Patients With Coronary Artery Disease
Authors: Hongwei Liu, Danielle A Southern, Ross Arena, Tolulope Sajobi, Sandeep Aggarwal, Stephen Wilton
Journal: Circulation (2020)

Introduction: Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Cardiac rehabilitation (CR) can reduce cardiovascular risk factors and improve CRF. However, the relationship between CR, CRF, and risk of incident atrial fibrillation (AF) in patients with cardiovascular disease is less clear. Objectives: To examine the association of CR completion and associated CRF changes with the incidence of new-onset AF in patients referred to a CR program after coronary revascularization. Methods and Results: We included 11,662 patients without a history of AF, referred to CR after coronary revascularization between January 1996 to March 2016. The mean age was 60.9 ± 10.9 years and 80.6% were males. Incident AF was ascertained by linkage with provincial administrative data sources and the local ECG repository. Competing-risks regression was used to estimate the association of CR completion and CRF with incident AF, with death as a competing event. During a median follow-up of 4.8 years, 618 patients developed AF, and 638 died. In adjusted models, CR completion was not associated with the risk of incident AF [Hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.83-1.15]. However, both baseline CRF [HR: 0.83; 95% CI: 0.76-0.90 per metabolic equivalent (MET)] and CRF gain (HR: 0.82; 95% CI: 0.72-0.94 per MET increase) for those who completed the CR program were associated with a lower risk of incident AF (Table 1). Conclusions: In patients referred to CR, CR completion was not associated with a reduced risk of incident AF. However, both higher baseline CRF and CR-associated CRF gains had a dose-dependent protective association with incident AF. Therefore, it is important to maximize CRF gains during the CR program. Further attention to AF-specific risk factor modification (i.e., obesity, sleep apnea, and alcohol) may be required to enhance CR program efficacy for this outcome, especially in patients with lower baseline CRF.
Abstract 12811: Clinical Outcomes and Prognostic Impact of Triglyceride Deposit Cardiomyovasculopathy Among Hemodialysis Patients Suspected of Coronary Artery Disease
Authors: Tomohiro Onishi, Yusuke Nakano, Ken-ichi Hirano, Yasuyuki Nagasawa, Atomu Tajima, Hideki Ishii, Hiroshi Takahashi, Hirohiko Ando, Shinichiro Sakurai, Hiroaki Takashima, Tetsuya Amano
Journal: Circulation (2020)

Introduction: Hemodialysis (HD) has been reported as a strong prognostic factor in patients with cardiovascular disease. It is unknown how much triglyceride deposit cardiomyovasculopathy (TGCV), a novel identified rare cardiovascular disorder, is associated with cardiovascular mortality among HD patients. Hypothesis: We hypothesized that comorbidity of TGCV in HD patients who suspected of CAD plays a critical role for cardiovascular outcomes in this population. Methods: We examined the data obtained from 83 consecutive HD patients suspected of coronary artery disease who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy and subsequent coronary angiography (CAG). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke up to 5 years of follow-up. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, target vessel revascularization, or any hospitalization for heart failure. Results: A total of 83 HD patients were grouped into either the definite TGCV (17 patients), the probable TGCV (22 patients), or the non-TGCV control group (44 patients). At the end of the follow-up period for a median of 4.7 years, a primary endpoint event occurred in 58.8% of the definite TGCV patients (hazard ratio, 8.06; 95% confidence interval [CI], 2.52-25.8, Log-rank p&lt;0.001) and 27.3% of the probable TGCV patients, as compared to 9.1% of the non-TGCV control patients; the corresponding rates of the key secondary endpoint were 88.2% for the definite TGCV patients (hazard ratio, 6.36; 95% CI, 2.89-14.0, Log-rank p&lt;0.001) and 59.1% for the probable TGCV patients. In the multivariate Cox proportional hazard analyses after adjustment for confounding factors, various variables related to mortality on HD patients, or variables known as a classical cardiovascular risk, the definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes in any of the three models. Conclusions: Comorbidity of TGCV in patients on HD was associated with increased risk of cardiovascular events including cardiovascular death, which might highlight the potential therapeutic target.
Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer
Authors: Hiroyuki Arai, Yi Xiao, Fotios Loupakis, Natsuko Kawanishi, Jingyuan Wang, Francesca Battaglin, Shivani Soni, Wu Zhang, Christoph Mancao, Bodour Salhia, Shannon M Mumenthaler, Daniel J Weisenberger, Gangning Liang, Chiara Cremolini, Alfredo Falcone, Joshua Millstein, Heinz-Josef Lenz
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunogenic cell death (ICD) is a tumor cell death involving both innate and adaptive immune responses. Given published findings that oxaliplatin, but not irinotecan, drives ICD, we investigated whether single nucleotide polymorphisms (SNPs) in the ICD pathway are associated with the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer (mCRC). Methods Two randomized clinical trials data were analyzed: discovery cohort, FOLFOX/bevacizumab arm (MAVERICC); validation cohort, FOLFOXIRI/bevacizumab arm (TRIBE); and two control cohorts, FOLFIRI/bevacizumab arms (both trials). Genomic DNA extracted from blood samples was genotyped. Ten SNPs in the ICD pathway were tested for associations with clinical outcomes. Results In total, 648 patients were included. In the discovery cohort, three SNPs were significantly associated with clinical outcomes in univariate analysis: CALR rs1010222 with progression-free survival (G/G vs any A, HR=0.61, 95% CI 0.43–0.88), ANXA1 rs1050305 with overall survival (OS) (A/A vs any G, HR=1.87, 95% CI 1.04–3.35), and LRP1 rs1799986 with OS (C/C vs any T, HR=1.69, 95% CI 1.07–2.70). Multivariate analysis confirmed the trend, but statistical significance was not reached. In the validation cohort, ANXA1 rs1050305, and LRP1 rs1799986 were validated to have the significant associations with clinical outcome. No significant associations of these SNPs were observed in the two control cohorts. Treatment-by-SNP interaction test confirmed the predictive values. Conclusions The predictive utility of ICD-related SNPs for the efficacy of oxaliplatin-based chemotherapy was demonstrated, warranting further validation studies to be translated into personalized treatment strategies using conventional cytotoxic agents in mCRC.
SP0023 Haemopoietic stem cell transplanation for severe autoimmune disease
Authors: A Tyndall
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Reporting on behalf of the EULAR and EBMT Autoimmune Disease Stem Cell Project. High dose immunoablative therapy with autologous haemopoietic stem cell transplantation (HSCT) has been used to treat selected patients with severe autoimmune disease (AD) in over 400 cases world wide.334 transplants (327 autologous) are registered in the combined EULAR/EBMT data base, target ADs and numbers being: multiple sclerosis-102, SSc-70, RA-41, JIA-35, SLE-25, dermatomyositis-6, Bechets-3, vasculitis 6 and others. Patients were from 78 transplant centres in 22 countries with a median follow up of 16(1–81) months. Four basic conditioning regimens were used in phase I and II pilot studies, with an unmanipulated graft product in 85 cases. A transplant related mortality (TRM) of 9% overall was observed, with inter disease differences (12.5% in SSc and only one TRM in RA). Around 2/3 of patients responded with improvement or stabilisation. In SSc, 69% achieved a 25% or greater improvement in skin score, and in secondary progressive MS, 78% a 3 year progression free survival. Relapse was more common with RA and JIA, mostly being a synovitis easy to control with agents which were ineffective pre transplant. Randomised, controlled prospective trials are underway in SSc (ASTIS Trial: HSCT versus monthly pulse cyclophosphamide)), and planned for RA and MS. Trials in JIA are being discussed and further phase I/II data are required for SLE and vasculitis. These will be presented, together with immune reconstitution data, sometimes predicting relapse, and new developments in HSCT, especially non myeloablative “mini” allograft techniques. This may be applicable to full sibling matched selected patients. <h3>Reference</h3> Biggs M, Passweg J, Furst D, <i>et al</i>. PhaseI/I trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis. 2001, in press
Abstract PO-048: Lack of L1CAM increases tumorigenicity, stemness and tumor fibrosis in pancreatic ductal adenocarcinoma
Authors: Donatella Delle Cave, Silvia Buonaiuto, Vincenza Colonna, Enza Lonardo
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of &amp;lt;8%, characterized by extensive fibrosis, which causes chemotherapy failure and tumor progression. Pancreatic stellate cells (PSCs) are the major cellular stromal component in PDAC, which contributes to extracellular matrix (ECM) deposition and tumor development. L1 cell adhesion molecule (L1CAM) expression is generally associated with metastases and poor prognosis in different human tumors, while its role in PDAC remains debated. We found that the majority of PDAC biopsies have reduced L1 expression that involves a more aggressive phenotype. We also found, in vitro, that the L1low cells had enhanced CSC features, including self-renewal, migration and chemoresistance. In vivo the L1low cells display augmented tumorigenic potential and were able to recapitulate the tumor heterogeneity compared to their L1high counterpart. Conversely, ectopic overexpression of L1 resulted in a consistent decrease in cell proliferation and reduction in the stem properties of tumor cells. This data indicates that restoration of L1 expression could counteracts the malignant behavior of the tumor cells, thus leading to a less aggressive phenotype. Mechanistically we found that the TGF-β1 secreted by the PSC increased in vitro the migratory potential and the resistance to gemcitabine of the PDAC cells through the reduction of L1 expression. PSC silenced for TGF-β1 were not able anymore to modulate the L1 expression, and in vivo when co-injected with PDAC cells do not sustain tumor formation as observed in the PSC control. The transcriptome profiling (by mRNA sequencing) of L1low cells revealed pathways associated with collagen secretion and degradation, suggesting that the absence of L1 in cancer cells concurs to the remodeling of the surrounding microenvironment. In vitro experiments with cancer cells knocked down for L1 showed an increase in collagen deposition, which contribute to enhance extracellular matrix (ECM) stiffness and tumor fibrosis. Interestingly, we demonstrated in co-culture experiments that the L1low PDAC cells stimulate the collagen production in PSC. By contrary, the overexpression of L1 has no significant effects on collagen production by PSC cells. Altogether these data demonstrate an intrigued cross-talk between PSC and PDAC cells, in which the PSCs represent a supportive niche for PDAC cells promoting their aggressiveness and stemness through the downregulation of L1CAM mediated by TGF-β1 and the secretion of collagen. Citation Format: Donatella Delle Cave, Silvia Buonaiuto, Vincenza Colonna, Enza Lonardo. Lack of L1CAM increases tumorigenicity, stemness and tumor fibrosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-048.