tbuckley/cabot-search huggingface dataset:
Abstract 16647: Surgical Cryoablation of Ventricular Tachycardia at the Time of LVAD Implantation
Authors: Erica S Zado, Pasquale Santangeli, Gregory Supple, Brian Betensky, Michael Riley, Pavan Atluri, Sanjay Dixit, Michael Acker, Francis E Marchlinski
Journal: Circulation (2015)

Introduction: Patients (pts) with advanced heart failure (HF) undergoing implantation of a left ventricular assist device (LVAD) are at high risk of recurrent ventricular tachycardia (VT). We report the outcome of surgical VT cryoablation (VT CA) at the time of LVAD insertion in pts with advanced HF and drug-refractory VT. Hypothesis: Outcome will be enhanced with pre-operative mapping. Methods: We included consecutive patients with advanced HF and recurrent VT refractory to antiarrhythmic drug therapy and/or conventional catheter ablation, who underwent LVAD implantation and concomitant surgical VT CA. Results: The cohort included 6 pts (5 [83%] male, age 62±10 years) with ischemic (4, 67%) or nonischemic (2, 33%) cardiomyopathy. The mean LVEF prior to surgery was 19±7% (10-27%). All patients had history of recurrent VT, with 4 (67%) pts presenting in VT storm. All were on amiodarone, 1 on oral and the others on IV amiodarone along with IV lidocaine prior to surgery. Four pts (67%) had preoperative detailed electroanatomic mapping (EAM) of the VT substrate, which was used to guide surgical ablation. Cryo lesions were deployed endocardially using the LV apical core as access and/or epicardially to areas identified as scar visually complemented by preop EAM when available (figure). There were no complications related to the CA. Over a follow-up 10.3±12.7 months (range 2-35 months), 4 pts (67%) had no VT, 1 pt had 2 ATP-terminated episodes at 2 months and 1 pt had significant reduction of VT burden (from 11 shocks before surgery to 1 shock at follow-up). The 2 pts with recurrences did not have pre-operative mapping prior to surgical ablation. One patient died of non-cardiac causes at 7 months and 2 patients underwent heart transplant at 10 and 35 months. Conclusions: In pts with advanced HF and refractory VT, surgical ablation can be safely and effectively accomplished at the time of LVAD implantation. When ablation is guided by pre-operative EAM, the outcome may be enhanced.
SAT0637 Radiographic and mri detected sacroiliitis is more often observed in patients with lumbosacral transitional vertebra in the desir cohort
Authors: G. Carvajal Alegria, M. Voirin-Hertz, F. Garrigues, A. Simon, A. Feydy, D. van der Heijde, M. Reijnierse, D. Loeuille, P. Claudepierre, T. Marhadour, A. Saraux
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lumbosacral transitional vertebra (LSTV) is a congenital anomaly of the lumbosacral transition reported in 16% to 36% of the general population. One study reported low clinical relevance of LSTV in the early diagnosis of axial spondyloarthritis (axSpA), but data remains scarce. <h3>Objectives</h3> Our objectives were to evaluate the association of LSTV with sacroiliitis on conventional radiographs (CR) and magnetic resonance imaging (MRI) in a population with inflammatory back pain (IBP) suspected of axSpA. <h3>Methods</h3> Baseline pelvic and lumbar CR of DESIR cohort patients (18–50 years, IBP≥3 months but &lt;3 years and suspicion of axSpA) were analysed by readers blinded to clinical and other radiologic information. Baseline sacroiliac joint MRI had been read for sacroiliitis according to the ASAS definition. Radiographic sacroiliitis was defined according to the modified New York classification (mNYc). Unilateral sacroiliitis was defined as at least grade 2 according to the mNYc. LSTV were defined on radiographs, according to Castellvi classification: 0 normal; 1 enlarged transverse processes (a=unilateral, b=bilateral); 2 pseudo-articulation with the sacral bone (a=unilateral, b=bilateral); 3 fusion with the sacral bone (a=unilateral, b=bilateral); 4 pseudo-articulation on one side and fusion on the other. Imaging data collected at inclusion were compared in patients with LSTV versus patients without using Chi-square test or exact Fischer’s test when appropriate. <h3>Results</h3> 688 patients with available CR enabling LSTV analysis were studied, 47% were men, mean age was 33 years, 64% fulfilled ASAS criteria. Among the 688 patients 29.1% presented LSTV. Number and percentages of patients with different classes of LSTV are presented in Table I. Patients with LSTV had more often sacroiliitis on CR than patients without, respectively 27% and 19% (p=0.013). Patients with LSTV had more often sacroiliitis on MRI (figure 1) than patients without, respectively 39% and 29% (p=0.019). Presence of fusion on the right transverse process was associated with both right (p=0.001) and left (p=0.001) sacroiliitis on CR. Presence of fusion on the left transverse process was associated with sacroiliitis in CR on both right (p=0.006) and left (p=0.001) sides. <h3>Conclusions</h3> LSTV is observed in 29.1% of patients from the DESIR cohort, as reported in the literature and is associated with sacroiliitis on conventional radiography and MRI. Further study is mandatory to understand if this is based on mechanical stress or AxSpA and to assess the potential bias of LSTV in axSpA diagnosis. <h3>Disclosure of Interest</h3> None declared
Age-Associated Deviations of Amygdala Functional Connectivity in Youths With Psychosis Spectrum Disorders: Relevance to Psychotic Symptoms
Authors: Maria Jalbrzikowski, Vishnu P. Murty, Brenden Tervo-Clemmens, William Foran, Beatriz Luna
Journal: American Journal of Psychiatry (2019)

Objective: The authors created normative growth charts of amygdala functional connectivity in typically developing youths, assessed age-associated deviations of these trajectories in youths with psychosis spectrum disorders, and explored how these disruptions are related to clinical symptomatology. Methods: Resting-state functional neuroimaging data from four samples (three cross-sectional, one longitudinal) were collected for 1,062 participants 10–25 years of age (622 typically developing control youths, 194 youths with psychosis spectrum disorders, and 246 youths with other psychopathology). The authors assessed deviations in the psychosis spectrum and other psychopathology groups in age-related changes in resting-state functional MRI amygdala-to-whole brain connectivity from a normative range derived from the control youths. The authors explored relationships between age-associated deviations in amygdala connectivity and positive symptoms in the psychosis spectrum group. Results: Normative trajectories demonstrated significant age-related decreases in centromedial amygdala connectivity with distinct regions of the brain. In contrast, the psychosis spectrum group failed to exhibit any significant age-associated changes between the centromedial amygdala and the prefrontal cortices, striatum, occipital cortex, and thalamus (all q values <0.1). Age-associated deviations in centromedial amygdala–striatum and centromedial amygdala–occipital connectivity were unique to the psychosis spectrum group and were not observed in the other psychopathology group. Exploratory analyses revealed that greater age-related deviation in centromedial amygdala–thalamus connectivity was significantly associated with increased severity of positive symptoms (r=0.19; q=0.05) in the psychosis spectrum group. Conclusions: Using neurodevelopmental growth charts to identify a lack of normative development of amygdala connectivity in youths with psychosis spectrum disorders may help us better understand the neural basis of affective impairments in psychosis, informing prediction models and interventions.
Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome
Authors: Helga Westerlind, Marie Holmqvist, Lotta Ljung, Thomas Frisell, Johan Askling
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. Methods By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996–2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations. Results We identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations. Conclusion Siblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).
A Novel Point-of-Care Whole Blood Coagulation Assay to Monitor Emicizumab Therapy in Patients with Hemophilia
Authors: Michael A Suster, Debnath Maji, Lalitha V. Nayak, Christina Jenkins, Susan Hunter, Alvin H. Schmaier, Pedram Mohseni, Sanjay Ahuja
Journal: Blood (2018)
Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins
Authors: ChangDong Lin, YouHua Zhang, Kun Zhang, YaJuan Zheng, Ling Lu, HaiShuang Chang, Hui Yang, YanRong Yang, YaoYing Wan, ShiHui Wang, MengYa Yuan, ZhanJun Yan, RongGuang Zhang, YongNing He, GaoXiang Ge, Dianqing Wu, JianFeng Chen
Journal: Immunity (2019)
Bariatric/Metabolic Surgery for Diabetes: Lessons From the Past and Present
Authors: Jonathan Q. Purnell, Bruce M. Wolfe
Journal: Diabetes Care (2019)

One of the most important breakthroughs in diabetes was announced in 1921 by a surgeon-led team working on the gastrointestinal tract. Frederick Banting, a general surgeon in Canada, partnered with a physiologist, John Macleod, and others to purify insulin from pancreatic extracts and demonstrated that this gut hormone could treat diabetes. Eighty years later, more than 30 gut-derived hormones have been described (1), many of which have also been shown to influence glucose as well as lipid metabolism, appetite control, and energy expenditure. And these are just the ones we know about.

Despite its gastrointestinal origins, research into the mechanisms of insulin’s action and its use for the treatment of diabetes became the domain of endocrinologists, who to this day, it may be argued, have otherwise ignored the largest endocrine organ in the body to focus on the five or six hypothalamic-pituitary axes. As a result of these efforts, diabetes is now understood to be a chronic disease that manifests when too little insulin is secreted by pancreatic islets in response to the body’s needs: an absolute deficiency in the case of type 1 diabetes and a relative insulin deficiency in type 2 diabetes. It is frustrating that, despite nearly 100 years of research since insulin’s discovery, the specific causes of insulin resistance and impaired insulin secretion that lead to diabetes remain largely elusive.

Enter the surgeons again. Starting in the latter half of the last century, obesity became an increasingly prevalent medical problem in the U.S. and other developed nations. As obesity rates have risen, so has our understanding of the importance of excess fat storage in expression of …
AB0148 Extracellular vesicle-mediated delivery of ebv small rna (EBER1) activates lupus nephritis related antiviral immunity in tubular epithelial cells via tlr3
Authors: R. Baglio, N. Masoumi, M. Tsang a Sjoe, M. Eijndhoven, K. Jordanova, K. Heutink, K. de Wildt, N. Groenewegen, R. Ten Berge, R. Schiffelers, J. van Weering, S. Verkuijlen, I. Bultink, J. Middeldorp, J. Roelofs, A.E. Voskuyl, M. Pegtel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In lupus nephritis (LN), genetic and environmental factors drive the chronic activation of antiviral defenses leading to immune complex-mediated glomerular and tubular damage. Increasing evidence suggests the involvement of extracellular vesicles (EVs) in autoimmune disease. Currently a role for EVs in the pathogenesis of lupus nephritis has not been proposed. <h3>Objectives</h3> To investigate the role of EVs in the pathogenesis of LN. <h3>Methods</h3> To determine the presence of EVs in kidneys, biopsies from LN patients and IgA- nephropathy and Focal Segmental Glomerulosclerosis control patients were used. Serum samples from SLE patients and from RA patients as controls were used to determine the presence of circulating EVs. Primary renal tubular epithelial cells (TEC) were cultured, and Kidney injury molecule-1 (KIM1) expression was assessed by FACS. Exosomes were analyzed by electron microscopy and western blot. mRNA analysis was performed by qPCR. TLR3 inhibition was performed with TLR3/dsRNA complex inhibitor and with hydroxychloroquine. <h3>Results</h3> We show that EVs deliver virus-derived small RNA and activate TEC via toll-like receptor 3 (TLR3). Highly specific stem-loop RT-PCRs revealed Epstein Barr Virus (EBV)-encoded small RNAs in LN biopsies while quantitative EBV-DNA PCR, sensitive to a single copy was negative. In situ hybridization failed to detect nuclear EBV-EBER1 (i.e. EBV-infected cells) in LN biopsies. However, we observed atypical EBER signal in the cytoplasm of TECs in LN but not in disease control biopsies, suggestive of uptake of extra-renal EBER. Consistent with this, we detected EBER1 in circulating EVs of SLE sera. The LN tissues express strongly elevated levels of TLR3, Interferon induced transmembrane-1 and -3, and TNFα. Primary TEC cultured in vitro endocytose EBER1-EVs secreted by EBV-infected B cells via phosphatidylserine receptors such as KIM-1. Importantly, EV-EBER1 uptake by TEC triggers antiviral immunity and pro-inflammatory cytokine secretion in a Toll-like receptor 3 (TLR3)-dependent manner. Treatment with hydroxychloroquine (HCQ) or a small molecule inhibitor that blocks TLR3-RNA interactions strongly reduced the pro-inflammatory effects of EBER1. <h3>Conclusions</h3> We propose that small RNA-loaded EVs exacerbate pre-existing autoimmunity in SLE patients by engaging tubular epithelial TLR3, supporting the rationale for TLR3-blockade as therapeutic strategy in the treatment of lupus nephritis. <h3>Disclosure of Interest</h3> None declared
Pulmonary rehabilitation for bronchiectasis: if not now, when?
Authors: Mark L. Metersky, Richard L. ZuWallack
Journal: European Respiratory Journal (2019)

<b>This study provides robust evidence that outpatient pulmonary rehabilitation is effective in patients with bronchiectasis: it is time to increase the use of this under-utilised intervention</b>http://ow.ly/3tle30ndsZq
Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder
Authors: Jody L. Greaney, Erika F.H. Saunders, Lakshmi Santhanam, Lacy M. Alexander
Journal: Circulation Research (2019)

In rodent models of depression, oxidative stress-induced reductions in NO bioavailability contribute to impaired endothelium-dependent dilation. Endothelial dysfunction is evident in major depressive disorder (MDD); however, the molecular mediators remain undefined.We sought to translate preclinical findings to humans by testing the role of oxidative stress in mediating microvascular endothelial dysfunction, including potential modulatory influences of sex, in MDD.Twenty-four treatment-naive, otherwise healthy, young adults with MDD (14 women; 18-23 years) and 20 healthy adults (10 women; 19-30 years) participated. Red blood cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine, alone and in combination with an NO synthase inhibitor (L-NAME), a superoxide scavenger (Tempol), and an NADPH oxidase inhibitor (apocynin), as well as during perfusion of the endothelium-independent agonist sodium nitroprusside. Tissue oxidative stress markers (eg, nitrotyrosine abundance, superoxide production) were also quantified. Endothelium-dependent dilation was blunted in MDD and mediated by reductions in NO-dependent dilation. Endothelium-independent dilation was likewise attenuated in MDD. In MDD, there were no sex differences in either NO-mediated endothelium-dependent dilation or endothelium-independent dilation. Acute scavenging of superoxide or inhibition of NADPH oxidase improved NO-dependent dilation in MDD. Expression and activity of oxidative stress markers were increased in MDD. In a subset of adults with MDD treated with a selective serotonin reuptake inhibitor for their depressive symptoms and in remission (n=8; 7 women; 19-37 years), NO-mediated endothelium-dependent dilation was preserved, but endothelium-independent dilation was impaired, compared with healthy adults.Oxidative stress-induced reductions in NO-dependent dilation, as well as alterations in vascular smooth muscle function, directly contribute to microvascular dysfunction in MDD. Strategies targeting vascular oxidative stress may be viable therapeutic options for improving NO-mediated endothelial function and reducing cardiovascular risk in MDD.
THU0431 Are extremity telangiectases related to severe disease in systemic sclerosis ?
Authors: Y. Yalçınkaya, O. Pehlivan, Z. Ertürk, U. Gazel, A. Aksoy, F. Alibaz-Oner, P. Atagunduz, H. Direskeneli, N. Inanc
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The number and morphology of telangiectases (T) have been studied in terms of severity and organ involvement in sytemic sclerosis (SSc). T are located more frequently on face and trunk than extremities. <h3>Objectives</h3> We aimed to evaluate the impact of the localisation of T on different skin areas in addition to number on disease severity of SSc. <h3>Methods</h3> SSc patients fulfilling ACR/EULAR classification criteria (2013) who had the manifestation T were included. The number of T were calculated by using telangiectasia score (TS) (Shah A., et al) and localisation was classified according to presence of T on extremities or not. Simultaneously; ealy, active and late scleroderma patterns (Cutolo et al.) were determined qualitatively and capillary number (CN) was calculated per linear mm at distal row quantitatively by using nail fold video-capillaroscopy (NVC) in all patients. <h3>Results</h3> In 113 (106 female) SSc patients with T; the mean age was 52±12, the duration of follow-up 57±62 months, Raynaud and non-Raynaud symptom 10±8 and 7±7 years. Limited cutaneous form was found to be in 77 (%68), ANA positivity in 102 (%90) ve anti-Scl70 positivity in 33 (%29) patients. In SSc patients with TS score ≥6 or extremity T; the duration of non-Raynaud symptom was found to be longer (p=0010 or 0,009), MRSS and activity scores were higher (p=0004 or 0012 and p=0010 or 0,009) and severity scores of general, peripheral vascular involvement and skin were higher (p=0022 or 0,014, p=0030 or 0025 and p=0006 or 0,02), digital ulcers and flexion contractures were more frequent (p=0008 or 0035 and p=0027 or 0,032), late NVC pattern was more frequent and CN was lower (p=0001 or 0003 and p=0001 or 0,007). When patients were classified in 3 groups according to TS and presence of extremity T, differences in terms of organ involvement, disease activity and severity scores and NVC findings were summarised in table 1. <h3>Conclusions</h3> Disease duration was shown to be long, disease activity and severity were high and NVC findings were severe in patients with high scores of TS and extremity T. In patients with lower TS the presence of T on extremities was found to be related to severe disease. The number and localisation of T was emphasised as they are easy to evaluate in clinical practice and may be useful in determining severe patients with SSc. <h3>Disclosure of Interest</h3> None declared
Comparison of Mitoxantrone-Based Salvage Therapies (MEC vs CLAG-M) in Relapsed or Refractory Acute Myeloid Leukemia
Authors: Caleb J Scheckel, Jeffrey Alan Betcher, Lisa Sproat, Raoul Tibes, James L. Slack, Jose F. Leis, Pierre Noel, Lanyu Mi, Jeanne Palmer
Journal: Blood (2017)
SAT0375 Impact of febuxostat on renal function among gout patients with different renal function
Authors: T.-T. Chung, C.-F. Kuo, J.-S. Chen, M.-J. Chiou
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Febuxostat is a new xanthine oxidase inhibitor which is effective in the treatment of hyperuricemia. Its use in people with different levels of renal function has not been thoroughly assessed. <h3>Objectives</h3> To assess the risk of renal function deterioration in gout patients using febuxostat and compare it with patients using allopurinol and other uricosuric agents. <h3>Methods</h3> We included 5882 adult patients with gout diagnosed between 2012 and 2015. We divided patients into three groups by usage of urate-lowering drugs used (allopurinol, febuxostat and uricosuric agents including benzbromarone, probenecid and sulfinpyrazone). The primary outcome was a progress of one chronic kidney disease (CKD) stage. The index date was the first date of urate-lowering drugs used. We follow each patient to the date of event, death, switch to other drug or the end of the study. The Cox proportional hazards model was used to estimate the adjusted hazard ratios (HRs), adjusted for age, sex, baseline eGFR, baseline serum urine acid, comorbidity, co-medication. <h3>Results</h3> The incident rate of the renal function deterioration was 2.37 (95% CI, 1.75–3.14) per 1000 person-days in allopurinol users, 1.54 (95% CI, 1.30–1.81) per 1000 person-days in febuxostat users and 1.43 (95% CI, 1.32–1.56) per 1000 person-days in uricosuric agent users. The HRs of progession of CKD stage in febuxostat and uricosuric agent users were 0.98 (95% CI, 0.70–1.38) and 0.80 (95% CI, 0.59–1.09) compared with allopurinol. Among febuxostat users, the HRs were 1.80 (95% CI, 0.85–3.98) in patients with an estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m<sup>2</sup>), 1.06 (95% CI, 0.56–2.03) for patients with an eGFR 60–89 ml/min/1.73 m<sup>2</sup>, 0.78 (95% CI, 0.45–1.42) for patients with an eGFR 30–59 ml/min/1.73 m<sup>2</sup> and 0.73 (95% CI, 0.22–3.52) for patients with an eGFR 15–29 ml/min/1.73 m<sup>2</sup>. Among uricosutic agent users, the HRs were 0.94 (95% CI, 0.52–1.88) in patients with an eGFR ≥90 ml/min/1.73 m<sup>2</sup>, 0.88 (95% CI, 0.55–1.50) in patients with an eGFR 60–89 ml/min/1.73 m<sup>2</sup>, 0.71 (95% CI, 0.41–1.28) in patients with an eGFR 30–59 ml/min/1.73 m<sup>2</sup> and 0.71 (95% CI, 0.19–3.62) in patients with an eGFR 15–29 ml/min/1.73 m<sup>2</sup>. <h3>Conclusions</h3> Renal function deterioration is not uncommon after initiation of urate-lowering treatment and febuxostat has a similar renal safety profile as allopurinols and uricosuric agents. <h3>Disclosure of Interest</h3> None declared