tbuckley/cabot-search huggingface dataset:
PS1095 RAPID INFUSION WITH CT-P10 IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA OR CHRONIC LYMPHOCYTIC LEUKAEMIA: INTERIM RESULTS FROM A EUROPEAN NON-INTERVENTIONAL POST-AUTHORISATION SAFETY STUDY
Authors: M. Bishton, S. Marshall, V. Conteh, A. Rodríguez Fernández, H. Kang, S. Kim, Y.N. Lee, P.L. Zinzani
Journal: HemaSphere (2019)

Background: T-cell directed therapies (e.g. CAR-T, blinatumomab) are associated with significant risk of Grade (Gr) ≥3 neurotoxicity and CRS/infusion-related reaction (IRR). Mosunetuzumab is a CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate malignant B-cells. Aims: To report safety results from an ongoing Phase 1/1b study (NCT02500407) of mosunetuzumab in patients (pts) with R/R B-cell NHL. Methods: Pts received ascending doses on Day 1, Day 8, and Day 15 of Cycle 1 (step-fractionation), then a fixed dose on Day 1 of every 21-day cycle thereafter, up to a maximum of 17 cycles. Primary outcome measures included safety and efficacy. Results: As of October 23, 2018, 114 pts who received step-fractionated dosing of mosunetuzumab were evaluable for safety (Table). The majority of adverse events (AE) occurred during Cycle 1 and 2. Neurologic AEs (NAE), defined from Nervous System or Psychiatric System Organ Classes, were mostly low grade, transient (median duration 4 days) and reversible; most common were headache (14%) and dizziness (8%). Gr ≥3 NAEs occurred in 4 pts (4%), with only 1 treatment-related event (hepatic encephalopathy). CRS/IRR was reported in 25% of pts, with only 1 Gr 3 event. Most common CRS symptoms were pyrexia (86%), chills (38%), tachycardia and headache (14% each). There were no Gr 5 events related to CRS or NAEs. No apparent dose toxicity relationship was observed with step-fractionation in these pts, despite escalation of the Cycle 1 Day 15 dose to 20 mg, consistent with observed peak IL-6 levels after a low Cycle 1 Day 1 dose. In these pts, objective responses were observed in 24/73 (33%; complete response [CR], 13 [18%]) aggressive NHL and 17/32 (53%; CR, 10 [31%]) indolent NHL pts.Summary/Conclusion: Step-fractionation has enabled continued dose escalation of mosunetuzumab with no apparent increases in toxicity, exhibiting a promising risk-benefit profile.
Abstract 19869: Relation Between Intramural Ablation Lesion Creation and Ablation Parameters in Humans
Authors: Shinichi Tanigawa, Akira Fujii, Tomofumi Nakamura, Benjamin Schaeffer, Saurabh Kumar, Nishaki Mehta, Sunil Kapur, Kathryn Finnerty, Daniele Ghigoli, Ihab Elsokkari, Amir AbdelWahab, Roy M. John, Usha B. Tedrow, John L. Sapp, William G Stevenson
Journal: Circulation (2017)

Introduction: Intramural substrate is a cause of failure of endocardial ablation that can be targeted by a novel needle ablation catheter. There is limited information to assess intramural lesions ...
Ohio doctor is charged with 25 counts of murder over patients’ deaths
Authors: Owen Dyer
Journal: BMJ (2019)

An intensive care physician in Columbus, Ohio, has been charged with 25 counts of murder, accused of prescribing lethal doses of fentanyl to critically ill patients in his care.

William Husel, 43, turned himself in for arrest and was later released on a $1m bond. He faces 25 charges of second degree murder, each with a maximum penalty of life imprisonment.

Husel was fired from his job at Mount Carmel Health System in December, after an internal inquiry found 35 cases in which he prescribed excessive doses, of which 29 were potentially fatal. Although most of his alleged victims were already near death, six might potentially have survived …
Abstract 12524: Changes in Pulmonary Autograft Wall Stresses Immediately After the Ross Operation: First Steps Towards Understanding Aneurysmal Remodeling
Authors: Andrew D Wisneski, Yue Xuan, Julius M Guccione, Liang Ge, Elaine E Tseng
Journal: Circulation (2016)

Introduction: Pulmonary autograft dilatation is the Achilles heel of the Ross operation, often necessitating reoperation. To understand normal and abnormal autograft remodeling, first biomechanical understanding of human autografts after exposure to systemic pressure is required. Our aim was to quantify biomechanical wall stresses on normal autografts after Ross operation prior to remodeling and dilatation. Hypothesis: Elevated pressure of systemic circulation results in increased autograft wall stress to drive biomechanical remodeling. Methods: We previously developed a normal human autograft model using micro-computed tomography to obtain zero-pressure luminal geometry. Material properties of normal human autografts (n=9) was obtained by bi-axial stretching. Patient-specific zero-pressure wall thickness was incorporated. Autograft diameter and wall stress were determined at pulmonic and systemic pressures using finite element analyses. Results: At systemic systole, mean autograft diameter was 35.0±1.7mm at sinuses and 33.4±1.3mm at sinotubular junction (STJ); while at pulmonary systole, they were 32.5±1.9mm and 30.5±1.4mm, respectively. Distensibility, percent change in diameter from diastole to systole, was 1.4% at systemic pressures versus 3.0% at pulmonary pressures. Peak von Mises wall stress was 581±449kPa at systemic systole compared to 89.7±65.3kPa at pulmonic systole. Average wall stress at systemic systole was 223±88.3kPa and at pulmonic systole was 37.4±16.8kPa (Fig 1). Conclusions: Normal human pulmonary autograft biomechanical responses to systemic pressure were quantified. Nearly 6 fold increase in peak and average wall stress was observed at systemic pressures. Regions of peak stresses were observed in the sinuses. This data will serve as a necessary control for future comparison to aneurysmal pulmonary autografts, and will enable better understanding of patient-specific risk for autograft dilatation.
Abstract 16945: Activation of the "Splenocardiac Axis" by Electronic and Tobacco Cigarettes in Otherwise Healthy Young Adults
Authors: Zachary Boas, Pawan Gupta, Roya Moheimani, May Bhetraratana, Fen Yin, Kacey Peters, Jeffrey Gornbein, Jesus Araujo, Johannes Czernin, Holly Middlekauff
Journal: Circulation (2017)

Background: The “Splenocardiac Axis” describes an inflammatory signaling network underlying acute cardiac ischemia, characterized by sympathetic nerve stimulation of hematopoietic tissues, such as ...
Abstract 16481: Timeline ("Chronology") and Clinical Correlates of Early Cardiovascular Events in Adults with Premature Artery Disease
Authors: Pavel J Levy, Hamza Rana, Jeanette S Andrews, Billy Chacko, Matthew Edwards, Kimberley J Hansen
Journal: Circulation (2012)

Background: The systemic nature of early subclinical atherosclerotic cardiovascular disease (ASCVD) is well established. Cardiovascular events in the young result mainly from coronary artery diseas...
AB0576 SERUM CATHELICIDIN (LL 37) LEVELS IN PATIENTS WITH BEHCET’S DISEASE AND ITS ASSOCIATION WITH DISEASE ACTIVITY
Authors: Melike Zelal Cakir, Pelin Oktayoglu, Nuriye Mete, Mehmet Caglayan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Behcet's disease (BD) is a recurrent multisystem inflammatory disease which is characterized by recurrent episodes of oral aphthous and genital ulcers, ocular inflammation and skin lesions. Anti-microbial peptides (AMPs) such as the cathelicidin (LL-37) and defensins have recently been implicated in the pathogenesis of autoimmune and autoinflammatory diseases. <h3>Objectives:</h3> The aim of this study was to investigate the serum levels of cathelicidin and its potential association with disease activity, and some other laboratory parameters such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), white blood cell count (WBC) in patients with BD. <h3>Methods:</h3> A total of 45 patients who presented to Dicle University Rheumatology clinics between September 2018 and December 2018 and met the International Study Group Classification Criteria for BD and 37 healthy control subjects who presented to Dicle University Physical Medicine and Rehabilitation clinics for various reasons other than rheumatoid complaints between the same dates were included in this study. Patients' demographic features, including age and sex, were noted. Duration of disease was also noted, and the disease activity was assessed by means of BD Current Activity Form (BDCAF). Laboratory investigations included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete blood count and routine biochemical analyses. Serum levels of cathelicidin (LL 37) were determined by means of human cathelicidin antimicrobial peptide ELISA Kit according to the manufacturer's protocol. <h3>Results:</h3> Serum mean level of cathelicidin (LL 37) in patients with BD was lower than healthy controls but this result was not statistically significant. Cathelicidin levels were not correlated with ESR, CRP, BDCAF and WBC (p&gt;0.05). <h3>Conclusion:</h3> However serum mean levels of cathelicidin (LL 37) were lower in patients with BD compared to healthy controls, this result was not statistically significant. It may may be sourced from our relatively small sample size. To validate cathelicidin (LL 37) value as a prognostic or pathophysiologic biomarker, future studies should investigate the levels of cathelicidin LL37 in patients with BD in large cohorts of patients with different levels of disease activity, remission, and relapse. <h3>Reference</h3> [1] Hoffmann MH, Bruns H, Backdahl L, et al. The cathelicidins LL-37 and rCRAMP are associated with pathogenic events of arthritis in humans and rats. Ann Rheum Dis. 2013;72(7):1239-48 [2] Gasim A. Cathelicidin antimicrobial peptide as a serologic marker and potential pathogenic factor in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Res Ther. 2014: 28;16(1):105 <h3>Disclosure of Interests:</h3> None declared
PF699 LUSUTROMBOPAG IS A SAFE TREATMENT OPTION FOR THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC LIVER DISEASE UNDERGOING A SCHEDULED INVASIVE PROCEDURE: POOLED SAFETY ANALYSIS FROM 3 STUDIES
Authors: R.S. Brown, N. Izumi, T. Kano, T. Ochiai, M. Kurosaki, F. Violi, P. Shrestha
Journal: HemaSphere (2019)

Background: Lusutrombopag is a thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing planned invasive procedures. In an integrated analysis of 2 Phase 3 studies, lusutrombopag reduced the need for platelet transfusions compared to placebo. Aims: Treatment with thrombopoietin receptor agonists has been associated with an increased risk of thrombotic events in patients with chronic liver disease. Thus, a thorough safety assessment of new agents is critical. A pooled retrospective analysis of 3 clinical studies was performed to assess safety of lusutrombopag. Methods: Safety data from 3 double‐blind, randomized, placebo‐controlled studies in patients with chronic liver disease and thrombocytopenia undergoing a scheduled invasive procedure (Phase 2b: M0626 [Japan; JapicCTI‐121944], Phase 3: L‐PLUS 1 [Japan; JapicCTI‐132323] and L‐PLUS 2 [global; NCT02389621]) were pooled. Adults with platelet counts &lt;50x10 9 /L at baseline received lusutrombopag 3 mg or placebo for up to 7 days before a procedure scheduled 9–14 days after randomization. Platelet transfusion was given if the platelet count remained &lt;50x10 9 /L no more than 2 days prior to procedure. Adverse event data were collected from signing of informed consent until the end of the post‐treatment period or early termination. Results: The pooled safety population included 341 patients (n = 171, lusutrombopag; n = 170 placebo). Approximately 65% of patients in the lusutrombopag and placebo groups experienced an adverse event ( Table ). Thrombotic and thromboembolic adverse events occurred in 1.8% (3/171) of lusutrombopag patients (cardiac ventricular thrombosis, n = 1 [patient had prior history of cardiac ventricular thrombosis]; portal vein thrombosis, n = 2) and 2.4% (4/170) of placebo patients (mesenteric vein thrombosis, n = 2; portal vein thrombosis, n = 2). Overall, bleeding‐related adverse events occurred in less lusutrombopag vs placebo patients (15 [8.8%] vs 27 [15.9%]), respectively. The 3 adverse events leading to death were not considered treatment‐related but due to the progression of underlying disease. Summary/Conclusion: In this pooled safety analysis, lusutrombopag was safe and well‐tolerated in patients with thrombocytopenia and chronic liver disease undergoing invasive procedures. Approximately 50% fewer bleeding‐related adverse events and no increased risk of thrombotic and thromboembolic adverse events were observed in patients treated with lusutrombopag vs placebo. image
Social and Mental Health Care Integration
Authors: Laura Shields-Zeeman, Cara Lewis, Laura Gottlieb
Journal: JAMA Psychiatry (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Abstract 3798: Impact of Worsening Renal Function During Hospitalization for Heart Failure on 30 Day Outcomes Among Medicare Beneficiaries in OPTIMIZE-HF
Authors: Uptal Patel, Melissa Greiner, Gregg C Fonarow, Adrian F Hernandez, Christopher O’Connor, Lesley H Curtis
Journal: Circulation (2009)

Background: While baseline renal disease is common in heart failure (HF), the impact of worsening renal function (WRF) on outcomes following hospitalization for HF is poorly understood. Methods: OP...
Survival Outcomes Among Patients With Gastric Adenocarcinoma Who Received Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery
Authors: Charles W. Kimbrough, Eliza Beal, Sherif Abdel-Misih, Timothy M. Pawlik, Jordan M. Cloyd
Journal: JAMA Surgery (2019)

This study assesses survival outcomes among patients with gastric adenocarcinoma who received hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery at US academic centers.
AB0081 NOVEL COOPERATION BETWEEN CCL26 AND CX3CL1 VIA CX3CR1 IN THE INJURY OF SMALL BILE DUCT IN PRIMARY BILIARY CIRRHOSIS
Authors: Yihan Cao, Xiaochuan Sun, Zhilei Chen, Shuo Zhang, Hua Chen, Fengchun Zhang, LI Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> CX3CL1-CX3CR1 pathway has been found to be critically involved in the pathogenesis of primary biliary cholangitis (PBC)<sup>1</sup>. As a novel ligand to CX3CR1, CCL26 can promote chemotaxis of CX3CR1+ immune cells but its role in PBC remains elusive<sup>2</sup>. <h3>Objectives</h3> This study aimed to explore the role of CCL26, together with CX3CL1-CX3CR1 pathway, in the pathogenesis of PBC. <h3>Methods</h3> We recruited 40 patients diagnosed with PBC in the Peking Union Medical College Hospital from Jan 2018 to May 2018 and 18 age and sex-matched healthy controls (HCs). Peripheral blood and liver tissue samples were collected. The plasma level of CX3CL1 and CCL26 were determined by ELISA. Flow cytometry was used to measure the percentage of CX3CR1+ cells in various subsets of PBMCs. The expression of CX3CL1 and CCL26 in liver tissues was revealed by immunohistochemical staining. Using ELISA and flow cytometry, the change of CX3CL1/CCL26-CX3CR1 pathway expression in human intrahepatic biliary epithelial cells (HIBECs) upon stimulation of various cytokines was studied. <h3>Results</h3> The plasma level of CX3CL1 and CCL26 was higher in patients with PBC than HCs with a P value of 0.044 and 0.104 respectively. The increased level of CCL26 was positively correlated with peripheral eosinophils, basophils and CRP level. In comparison with HCs, the expression of CX3CR1 was significantly higher in NKT-like and CD4+ T cells in PBC patients. In liver samples from PBC patients, CX3CL1 and CCL26 were significantly over-expressed in intrahepatic bile ducts and CCL26 also tended to be abundant in hepatocytes near portal areas and gradually weakened in distant regions. This distribution pattern was not observed in HCs. Upon stimulation of IFN-γ, the expression of CX3CR1 on HIBEC surface and CX3CL1 in culture supernatant was significantly up-regulated, while the expression of CCL26 was increased upon IL-4 and IL-13 stimulation. <h3>Conclusion</h3> CCL26 may cooperate with CX3CL1 to mediate the immune injury of intrahepatic bile ducts via CX3CR1 in PBC. <h3>References</h3> [1] Isse K, Harada K, Zen Y, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology. 2005;41(3):506-16. [2] Nakayama T, Watanabe Y, Oiso N, et al. Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1. J Immunol. 2010;185(11):6472-9. <h3>Disclosure of Interests</h3> None declared
PS1365 NEXT‐GENERATION OPTICAL MAPPING REVEALS LARGE GENETIC HETEROGENEITY IN MULTIPLE MYELOMA
Authors: A. Petrackova, R. Fillerova, J. Minarik, Z. Mikulkova, J. Balcarkova, P. Krhovska, T. Pika, P. Gajdos, M. Behalek, T. Papajik, E. Kriegova
Journal: HemaSphere (2019)

Background: Genetic heterogeneity in multiple myeloma (MM) affects not only the disease development but also therapeutic response and prognosis. Nowadays, karyotype and FISH are standard diagnostic tools for the detection of genetic aberrations in MM. However, comprehensive analysis of genome architecture, particularly structural variations (SVs), still remain a challenge. Aims: To study the genomic architecture of MM cells using a novel nanochannel technology based on optical mapping of high‐molecular weight DNA in order to refine genomic variability in human MM. Methods: We analysed five samples of bone marrow aspirates from patients with newly diagnosed MM. High‐molecular weight DNA was isolated from sorted MM cells, labelled by DLS chemistry and visualised by Saphyr optical system (BioNano Genomics). Created single molecules were de novo assembled into physical maps spanning whole genome based on known labelled specific motifs. After filtering of structural variants against the database of healthy controls, only rare de novo variants were analysed. Karyotype, FISH , and arrayCGH results were available for the enrolled patients and were compared to the results of optical mapping. Results: For all MM samples, the optical genome maps (480 Gbp) were assembled with an average effective coverage of 124X and aligned to a human reference genome (GRCh38). In our cohort, numerous copy number variations and large somatic SVs, including deletions, insertions, inversions, duplications and translocations, were identified (Table 1) with majority of SVs being deletions (∼60%). All genetic variants detected by arrayCGH were also confirmed by mapping. Additional SVs with novel intra‐ and inter‐chromosomal translocations and copy number variants were found in all patients, not detected by FISH/arrayCGH. Regarding novel translocations, majority were intra‐chromosomal (64%) within chromosomes 3, 4, 6, 14, 16, 17, and 18. Additional translocations (36%), detected only by mapping, involved unusual chromosomes in MM: t(2;8), t(3;6), t(3;12), t(6;8), t(6;17), t(8;9), and t(8;22). All samples carried novel SVs on chromosome 17, including two intra‐ (P1) and one inter‐chromosomal translocations (P2), insertions in four (P2‐P5) and deletions in two (P4‐P5) patients. Although no IGH locus rearrangements were detected by standard methods, monosomy on chromosome 14 within IGH locus was observed in four samples (P2‐P5) by mapping. The analyses of associations of SVs and affected genes with clinical characteristics are ongoing. Summary/Conclusion: A large spectrum of novel genomic rearrangements was detected in MM using next‐generation mapping technology, showing a high potential of optical maps for refinement of genomic variability in human MM. image Grant support: research grant Celgene, MZ ČR VES16–32339A, NV18–03–00500, MZ ČR – RVO (FNOl, 00098892)
Abstract 18527: Correction of Impaired Calmodulin Binding to Ryr2 as a Novel Therapy of Lethal Arrhythmia in the Pressure-Overloaded Heart Failure
Authors: Yoshihide Nakamura, Takeshi Yamamoto, Takayoshi Kato, Yoriomi Hamada, Go Fukui, Yoko Sufu, Takuma Nanno, Shigehiko Nishimura, Hironori Ishiguchi, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Journal: Circulation (2016)

Introduction: Calmodulin (CaM) plays a key role in modulating channel gating of cardiac ryanodine receptor (RyR2). Hypothesis: In this study, we hypothesized that RyR2 bound CaM plays a key role in...
AB1263 C-REACTIVE PROTEIN LEVEL AS A MARKER FOR DYSLIPIDEMIA, DIABETES, AND METABOLIC SYNDROME: RESULTS FROM THE KOREAN NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY:
Authors: Hyemin Jeong, Yeoung Hee Eun, In-Young Kim, Eun-Jung Park, Jaejoon Lee, Hyungjin Kim, Chan Hong Jeon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> High sensitivity C-reactive protein (hsCRP) C-reactive protein (CRP) is a marker of inflammation and increased hsCRP is reported in many diseases including cardiovascular disease, diabetes, metabolic syndrome, arthritis, and malignancies. <h3>Objectives:</h3> This study evaluated the association between hsCRP and comorbidities. <h3>Methods:</h3> A total of 5,887 (weighted n = 40,251,868) participants age 19 or older from the 2016 Korean National Health and Nutrition Examination Survey were included for analysis. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed according to the continuous variable of log hsCRP levels. <h3>Results:</h3> Mean age was 46.7 and mean hsCRP levels were 1.23mg/L. Mean hsCRP levels were higher in participants with cardiovascular diseases and cardiovascular risk factors, osteoarthritis, rheumatoid arthritis, pulmonary tuberculosis, and several cancers of gastric, colon, breast, and cervix than the general population. In multivariable analysis, hsCRP concentration was associated with increased prevalence of hypertriglyceridemia (OR 1.15, 95% CI 1.04-1.28, p = 0.007), diabetes (OR 1.20, 95% CI 1.05-1.37, p = 0.005), and metabolic syndrome (OR 1.22, 95% CI 1.11-1.35, p &lt; 0.001) after adjustment for socioeconomic and lifestyle characteristics. There was no significant association between hsCRP level and cancers. <h3>Conclusion:</h3> hsCRP was associated with increased risk of dyslipidemia, diabetes, and metabolic syndrome in the general population. <h3> Disclosure of Interests:</h3> None declared
DegNorm: normalization of generalized transcript degradation improves accuracy in RNA-seq analysis
Authors: Bin Xiong, Yiben Yang, Frank R. Fineis, Ji-Ping Wang
Journal: Genome biology (2019)

RNA degradation affects RNA-seq quality when profiling transcriptional activities in cells. Here, we show that transcript degradation is both gene- and sample-specific and is a common and significant factor that may bias the results in RNA-seq analysis. Most existing global normalization approaches are ineffective to correct for degradation bias. We propose a novel pipeline named DegNorm to adjust the read counts for transcript degradation heterogeneity on a gene-by-gene basis while simultaneously controlling for the sequencing depth. The robust and effective performance of this method is demonstrated in an extensive set of simulated and real RNA-seq data.