tbuckley/cabot-search huggingface dataset:
Abstract P120: Association Of Carotid Intima-Media Thickness With Brain MRI Markers In The Atherosclerosis Risk In Communities Neurocognitive Study (ARIC-NCS)
Authors: Wendy Wang, Faye L Norby, Alvaro Alonso, Rebecca F Gottesman, Michelle Meyer, David Knopman, Kevin J Sullivan, Clifford R Jack, Timothy M Hughes, Kamakshi Lakshminarayan, Pamela L Lutsey
Journal: Circulation (2021)

Background: Elevated carotid intima-media thickness (cIMT) and presence of carotid plaque are markers of atherosclerosis, which may be linked to structural brain injury. Using data from the ARIC-NCS cohort, we tested the hypotheses that greater cIMT and presence of carotid plaque at late midlife were each associated with presence of infarcts (lacunar and cortical) and cerebral microbleeds (lobar and subcortical), greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late life. Methods: We included 1,795 ARIC participants who had carotid ultrasounds in 1990-92 and brain MRI scans in 2011-13. Weighted linear regression was used for continuous (brain volume) outcomes, and weighted logistic regression for dichotomous outcomes (infarcts and cerebral microbleeds). Results: Participants were aged 57±6 years at baseline, 57% were female, and 23% were Black. Mean ± SD follow-up was 21±1 years. After multivariable adjustments, the highest quintile of cIMT in late midlife was associated with smaller deep grey matter volume (β [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (β [95% CI]: -0.10 [-0.20, -0.01]) in late life (Table). At baseline, 473 (26%) participants had carotid plaque present on their carotid ultrasound. Similar to cIMT, those with carotid plaque had smaller regional brain volumes than those without carotid plaque present (βs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep grey matter and temporal-parietal meta ROI volumes, respectively). No significant relations were observed with WMH volume, or the presence of any infarcts or cerebral microbleeds. Conclusion: Greater midlife cIMT and presence of carotid plaque were associated with smaller deep grey matter volume and cortical volume in a temporal-parietal meta ROI in later life. Contrary to our hypothesis, associations between midlife subclinical atherosclerosis and markers of vascular brain injury in later life were null.
TNFAIP8 (TIPE) Deficiency Exacerbates Acute Graft Versus-Host Disease in Murine Model
Authors: Reena Kumari, Senthilnathan Palaniyandi, Ethan Strattan, Katharina Kohler, Nashwan Jabbour, Joanna Dalland, Melissa Kesler, Gerhard Carl Hildebrandt
Journal: Blood (2017)
Interleukin‐34 Reprograms Glycolytic and Osteoclastic Rheumatoid Arthritis Macrophages via Syndecan 1 and Macrophage Colony‐Stimulating Factor Receptor
Authors: Katrien Van Raemdonck, Sadiq Umar, Karol Palasiewicz, Michael V. Volin, Hatem A. Elshabrawy, Bianca Romay, Chandana Tetali, Azam Ahmed, M. Asif Amin, Ryan K. Zomorrodi, Nadera Sweiss, Shiva Shahrara
Journal: Arthritis & Rheumatology (2021)

In rheumatoid arthritis (RA), elevated serum interleukin-34 (IL-34) levels are linked with increased disease severity. IL-34 binds to 2 receptors, macrophage colony-stimulating factor receptor (M-CSFR) and syndecan 1, which are coexpressed in RA macrophages. Expression of both IL-34 and syndecan 1 is strikingly elevated in the RA synovium, yet their mechanisms of action remain undefined. This study was undertaken to investigate the mechanism of action of IL-34 in RA.
In the Era of Chemoimmunotherapy, Relapse Post Autologous Stem Cell Transplantation for Follicular Lymphoma Is Associated with Prolonged Overall Survival. an Analysis By the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Stephen Robinson, Hervé Finel, Ariane Boumendil, Herve Tilly, Gilles Salles, Paolo Corradini, Roberto Cairoli, Robert Pytlik, Harry C. Schouten, Catharina Lewerin, Catherine Thieblemont, Bernd Metzner, Alessandro Rambaldi, Mark Ringhoffer, Robert Lown, Giuseppe Rossi, Jörg Thomas Bittenbring, Adrian Bloor, Árpád Illés, Pierre Feugier, Pascal Turlure, Ghulam Mufti, Thomas Heinicke, Karl Peggs, Xavier Poire, Peter Dreger, Silvia Montoto
Journal: Blood (2017)
Abstract 15792: Etiology, Treatment and Outcomes in Patients With Left Ventricular Thrombus - Experiences From an African Center
Authors: Mohamed Hasham Varwani, Mohamed Jeilan, Jasmit Shah, Leonard Ngunga
Journal: Circulation (2020)

Introduction: Left ventricular thrombus (LVT) may lead to thromboembolism and has been associated with increased morbidity and mortality. Little is known about the incidence, etiology and outcomes in patients with LVT in Africa. Objectives: To determine the etiology, treatment practices, rate of resolution and outcomes in patients with LVT in the region. Methods: A review of all echocardiograms performed in 2017 and 2018 at the Aga Khan University Hospital, Nairobi was carried out and patients with LVT identified. Physician review of charts was performed to document clinical characteristics and outcomes. Results: During the study period 100 patients with LVT were identified (1.3% of adult echoes). The mean LVEF was 28.5% (±11.0%) and 88% of the patients had an LVEF of less than 40%. Underlying etiology of LV dysfunction was post MI in 28%, chronic ischemic cardiomyopathy in 42% and non ischemic cardiomyopathy in 30%. In 15% of the patients a stroke or TIA predated the diagnosis of LVT. Long term anticoagulation was given to 92 patients. Among these, 37% received warfarin while 63% were treated with a DOAC (rivaroxaban (50%), dabigatran(7.6%) and apixaban(5.4%)). In 60% of the patients, anticoagulation was continued beyond a year. In patients with reassessment imaging (64%, median time 177 days), complete thrombus resolution was noted in 59.4%. One year follow-up data was available for 85 patients: 13 (15.3%) patients had died, 4 (4.7%) had suffered a stroke, and 8(9.4%) had a bleeding episode. Rates of thrombus resolution, stroke and bleeding were not significantly different among patients treated with warfarin and DOAC (Figure 1). Conclusions: We noted a high incidence of LVT compared to contemporary Western series. The majority of our patients were treated with DOACs. There were no significant differences in outcomes between patients treated with a DOAC and those receiving warfarin. Prospective evaluation on the efficacy and safety of DOACs for this indication is needed.
Abstract 15556: Clinical Outcomes After Routine Cox-MAZE IV and Appendectomy and Aggressive Left Atrial Plication Added to Mitral Valve Repair for Atrial Functional Mitral Regurgitation
Authors: Naoko Ikeda, Kohei Wakabayashi, Kaoru Tanno, Hiroki Yamaguchi
Journal: Circulation (2020)

Introduction: Atrial functional mitral regurgitation (AFMR) is one of the significant factors to worsen the outcomes in heart failure. The optimal therapy for AFMR is still controversial. Previous studies reported AFMR patients underwent mitral valve repair alone frequently had heart failure re-hospitalization or stroke after surgery. New guidelines recommend adding surgical ablation as a concomitant procedure for class I indications. However, many surgeons avoid concomitant procedure especially in patients with extremely enlarged left atrium (LA) and long atrial fibrillation (AF) duration. Hypothesis: Routine strategy of adding surgical ablation and appendectomy and aggressive LA plication to mitral valve repair might improve the outcomes with keeping sinus rhythm and without stroke events in AFMR patients. Methods and Results: We investigated 35 consecutive patients with severe AFMR who underwent surgery in our institute between 2014 and 2018. Our strategy was Cox-maze IV and appendectomy for all patients and if LA volume was more than 200 ml by echocardiography, we added LA plication. In addition to clinical data and conventional echocardiographic assessment (Table), left ventricular (LV) function was evaluated using 2D speckle tracking echocardiography. MR grade improved in all patients. Despite enlarged LA, 76% of patients regained sinus rhythm and atrial kick was detected by pulse doppler method (mean value: 55 ± 19 cm/s). After 2-year follow-up, LV global longitudinal strain and LA peak strain were significantly improved (Table). During 4.1 ± 1.3 years observation, no patient experienced heart failure re-hospitalization and stroke. Conclusions: Majority of AFMR patients had long duration of AF and severely enlarged LA. The routine Cox-maze IV, appendectomy and aggressive LA plication in enlarged LA patients improved LV and LA function. This strategy may contribute to the better long-term outcomes of AFMR compared to mitral valve repair alone.
All-Cause and Cancer-Specific Death of Older Adults Following Surgery for Cancer
Authors: Tyler R. Chesney, Natalie Coburn, Alyson L. Mahar, Laura E. Davis, Victoria Zuk, Haoyu Zhao, Amy T. Hsu, Frances Wright, Barbara Haas, Julie Hallet, Ines Menjak, Douglas Manuel, Dov Gandell, Lesley Gotlib-Conn, Grace Paladino, Pietro Galluzzo
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Cancer care has inherent complexities in older adults, including balancing risks of cancer and noncancer death. A poor understanding of cause-specific outcomes may lead to overtreatment and undertreatment. <h3>Objective</h3> To examine all-cause and cancer-specific death throughout 5 years for older adults after cancer resection. <h3>Design, Setting, and Participants</h3> This population-based cohort study was conducted in Ontario, Canada, using the administrative databases stored at ICES (formerly the Institute for Clinical Evaluative Sciences). All adults 70 years or older who underwent resection for a new diagnosis of cancer between January 1, 2007, and December 31, 2017, were included. Patients were followed up until death or censored at date of last contact of December 31, 2018. <h3>Exposures</h3> Cancer resection. <h3>Main Outcome and Measures</h3> Using a competing risks approach, the cumulative incidence of cancer and noncancer death was estimated and stratified by important prognostic factors. Multivariable subdistribution hazard models were fit to explore prognostic factors. <h3>Results</h3> Of 82 037 older adults who underwent surgery (all older than 70 years; 52 119 [63.5%] female), 16 900 of 34 044 deaths (49.6%) were cancer related at a median (interquartile range) follow-up of 46 (23-80) months. At 5 years, estimated cumulative incidence of cancer death (20.7%; 95% CI, 20.4%-21.0%) exceeded noncancer death (16.5%; 95% CI, 16.2%-16.8%) among all patients. However, noncancer deaths exceeded cancer deaths starting at 3 years after surgery in breast, prostate, and melanoma skin cancers, patients older than 85 years, and those with frailty. Cancer type, advancing age, and frailty were independently associated with cause-specific death. <h3>Conclusions and Relevance</h3> At the population level, the relative burden of cancer deaths exceeds noncancer deaths for older adults selected for surgery. No subgroup had a higher burden of noncancer death early after surgery, even in more vulnerable patients. This cause-specific overall prognosis information should be used for patient counseling, to assess patterns of over- or undertreatment in older adults with cancer at the system level, and to guide targets for system-level improvements to refine selection criteria and perioperative care pathways for older adults with cancer.
Patient preferences for stratified medicine in psoriasis: a discrete choice experiment*
Authors: G. Dalal, S.J. Wright, C.M. Vass, N.J. Davison, G. Vander Stichele, C.H. Smith, C.E.M. Griffiths, K. Payne
Journal: British Journal of Dermatology (2021)

Background New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients' preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. Objectives To quantify patient preferences for an algorithm-based approach to prescribing biologics ('biologic calculator') in psoriasis. Methods An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. Results Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. Conclusions This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic.
Abstract 14595: Characteristics of Patients With Primary Mitral Regurgitation With Early Failure of Mitral Valve Repair: A Matched Comparison Study
Authors: Agostina M Fava, A Marc Gillinov, Per Wierup, Brian P Griffin, Milind Y Desai
Journal: Circulation (2019)

Background: Mitral valve repair (MVr), performed for primary mitral regurgitation (PMR) has excellent long-term durability. However, occasionally, there is failure of MVr requiring a reoperation. W...
Visual intracortical and transthalamic pathways carry distinct information to cortical areas
Authors: Antonin Blot, Morgane M. Roth, Ioana Gasler, Mitra Javadzadeh, Fabia Imhof, Sonja B. Hofer
Journal: Neuron (2021)

Sensory processing involves information flow between neocortical areas, assumed to rely on direct intracortical projections. However, cortical areas may also communicate indirectly via higher-order nuclei in the thalamus, such as the pulvinar or lateral posterior nucleus (LP) in the visual system of rodents. The fine-scale organization and function of these cortico-thalamo-cortical pathways remains unclear. We find that responses of mouse LP neurons projecting to higher visual areas likely derive from feedforward input from primary visual cortex (V1) combined with information from many cortical and subcortical areas, including superior colliculus. Signals from LP projections to different higher visual areas are tuned to specific features of visual stimuli and their locomotor context, distinct from the signals carried by direct intracortical projections from V1. Thus, visual transthalamic pathways are functionally specific to their cortical target, different from feedforward cortical pathways, and combine information from multiple brain regions, linking sensory signals with behavioral context.
Severe thrombocytopenia from temozolomide (TMZ) in newly diagnosed patients with high-grade gliomas.
Authors: David E. Gerber, Stuart A. Grossman
Journal: Cancer Research (2006)

5283  BACKGROUND: Standard therapy for patients with newly diagnosed glioblastoma multiforme now includes temozolomide (TMZ) (75 mg/m2/day) administered with radiation therapy (RT) for 6 weeks, followed by 6 cycles of adjuvant TMZ (150-200 mg/m2/day for 5 days during each 28-day cycle). In the phase III clinical trial of this regimen (Stupp et al., NEJM 2005), thrombocytopenia was reported to be modest (12% grade 3/4) over the 8.5 months of planned treatment, and most cases (73%) of grade 3/4 thrombocytopenia developed during the monthly adjuvant cycles of TMZ. In this study, we further characterize the thrombocytopenia associated with this therapy. METHODS: A retrospective chart review was conducted of 52 consecutive patients with newly diagnosed high-grade gliomas treated with this regimen at The Johns Hopkins Hospital between June 2004 and October 2005. RESULTS: The median age of these patients was 57 years, and 54% were male. Almost all patients received corticosteroids, anticonvulsants, and trimethoprim-sulfamethoxazole. Histology included glioblastoma multiforme (73%), anaplastic astrocytoma (21%), and anaplastic oligodendroglioma (6%). Grade 3/4 thrombocytopenia was seen in 10 patients (19%). Five patients (10%) required platelet transfusions (range 1-59 transfusions). Two patients (4%) never recovered platelet counts, requiring biweekly platelet transfusions for over 6 months. In these patients, bone marrow evaluation demonstrated absent megakaryocytes. Therapy was discontinued in 9 patients (17%) because of thrombocytopenia. The median time to onset of grade 3/4 thrombocytopenia was 52 days, and the median duration was 32 days (range 1-217 days). Most cases (80%) of grade 3/4 thrombocytopenia developed during the daily TMZ and RT segment of therapy. Grade 3/4 thrombocytopenia occurred in 25% of women and 14% of men on this regimen and was not associated with age, renal or hepatic function, body surface area, use of anticonvulsants or antibiotics, or tumor histology. Grade 3/4 neutropenia (10%) and anemia (10%) had much less impact on the clinical course of these patients. CONCLUSIONS: This treatment regimen can result in severe and potentially irreversible thrombocytopenia. The factors that predispose certain patients to this toxicity have yet to be determined.
Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors
Authors: Tomoko Kobayashi, Shintaro Iwama, Daisuke Sugiyama, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Sachiko Ito, Mariko Sugiyama, Takeshi Onoue, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Hiroyoshi Nishikawa, Hiroshi Arima
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Pituitary dysfunction is a life-threatening immune-related adverse event (irAE) induced by immune checkpoint inhibitors (ICIs). To date, it is not possible to identify patients who may develop pituitary irAEs prior to ICI treatment. The aim of this study was to characterize the predisposition for ICI-induced pituitary irAEs by analyzing anti-pituitary antibodies (APAs) and human leukocyte antigens (HLAs). Methods In this case–control study, APAs and HLA alleles were analyzed in 62 patients (17 who developed ICI-induced isolated adrenocorticotropic hormone deficiency (ICI-IAD), 5 who developed ICI-induced hypophysitis (ICI-H) and 40 who did not develop pituitary irAEs) treated with ICIs between November 2, 2015, and March 31, 2020, at Nagoya University Hospital. The main outcome measures in this study were the association between the development of pituitary irAEs with APAs at baseline and after treatment and HLA alleles. Results Eleven of 17 (64.7%) patients who developed ICI-IAD had APAs at baseline, whereas APAs were positive only in 1 of 40 (2.5%) control patients. Although APAs were negative at baseline in all patients who developed ICI-H, they had become positive before the onset of ICI-H in 3 of 4 patients several weeks after ipilimumab administration. At the onset of ICI-IAD and ICI-H, APAs were positive in 15 of 17 (88.2%) and 4 of 5 (80%) patients, respectively. The prevalence of HLA-Cw12, HLA-DR15, HLA-DQ7, and HLA-DPw9 was significantly higher in patients with ICI-IAD, whereas that of HLA-Cw12 and HLA-DR15 was significantly higher in patients with ICI-H than in controls. Conclusions This study showed distinct and overlapped patterns of APAs and HLA alleles between ICI-IAD and ICI-H. Our findings also showed that positive APAs at baseline and after treatment, together with susceptible HLA alleles, could become predictive biomarkers for ICI-IAD and ICI-H, respectively. Trial registration number UMIN000019024.
Abstract 12991: Growth Differentiation Factor-15 is a New Predictor of Cardiovascular Events in Atrial Fibrillation Patients After Elective Percutaneous Coronary Intervention
Authors: Elena Krivosheeva, Ekaterina Kropacheva, Elena Titaeva, Anatoly Dobrovolsky, Anatoly Samko, Elizaveta Panchenko
Journal: Circulation (2020)

Introduction: Patients (pts) with AF, undergoing elective PCI, receiving multicomponent antithrombotic therapy (MAT) have high risk of stroke/systemic embolism and coronary events. There is no biochemical markers associated with negative prognosis in AF pts after elective PCI. Growth differentiation factor-15 (GDF-15) has demonstrated strong relationship with adverse prognosis in pts with cardiovascular disease. Purpose: To investigate the prognostic value of GDF-15 level in AF pts after elective PCI. Methods: 150 pts (104 males), aged 70.8±8.5 years, with AF after elective PCI were enrolled in the prospective study. All pts received DOACs and double (89.3%) or single (10.7%) antiplatelet therapy. Median duration of follow up period was 11.5 months [IQR 8.0; 12.0]. Efficacy endpoint of the study was the sum of cardiovascular events (CVE): ACS, ischemic stroke (IS), VTE, cardiovascular death and need for unplanned PCI. Plasma samples for GDF-15 were analyzed using ELISA. Results: AF pts receiving MAT demonstrated high thrombotic risk (CHA 2 DS 2 -VASc, Med 5 [IQR 4; 6]), high rate of comorbidity (index Charlson, Med 7 [IQR 5; 9]). Frequency of CVE during follow up period was 16% (ACS 2; fatal IS 2; VTE 2, include 1 fatal pulmonary embolism; cardiovascular death 2; pts needed an unplanned PCI 16). Median GDF-15 level was 1270 pg/ml [IQR 953; 1778]. According to multiple regression analysis GDF-15 level was associated with the D-dimer (t=3.20; p=0.0018), diabetes mellitus (t=3.97; p=0.0001) and clinical and angiographic Syntax II score (t=4.77; p&lt;0.0001). In pts with only coronary artery disease, the level of GDF-15 was significantly lower than in pts with atherosclerotic lesion of 3 vascular pools (p=0,0119). According to ROC analysis GDF-15 level &gt; 1191 pg / ml (sensitivity 83.0, specifity 50.0) increase the probability of the development of CVE (AUC=0.647, p=0.0076, 95% CI 0.565–0.723). Kaplan-Meier curves demonstrated significant difference in CVE free survival between the patients with GDF-15 level &gt; and ≤ 1191 pg/ml (75.9% and 94.0% respectively, log-rank test p = 0.0032, [HR 4.36, CI 1.50-7.48]). Conclusions: GDF-15 is a possible marker of CVE determining prognosis in AF pts after elective PCI. The results could be used to individualize the duration of MAT.