tbuckley/cabot-search huggingface dataset:
Geriatric Assessment, Not ASA Physical Status, Is Associated With 6-Month Postoperative Survival in Patients With Cancer Aged ≥75 Years
Authors: Armin Shahrokni, Bella Marie Vishnevsky, Brian Jang, Saman Sarraf, Koshy Alexander, Soo Jung Kim, Robert Downey, Anoushka Afonso, Beatriz Korc-Grodzicki
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The American Society of Anesthesiologists physical status (ASA PS) classification system is the most common method of assessing preoperative functional status. Comprehensive geriatric assessment (CGA) has been proposed as a supplementary tool for preoperative assessment of older adults. The goal of this study was to assess the correlation between ASA classification and CGA deficits among oncogeriatric patients and to determine the association of each with 6-month survival. Patients and Methods: Oncogeriatric patients (aged ≥75 years) who underwent preoperative CGA in an outpatient geriatric clinic at a single tertiary comprehensive cancer center were identified. All patients underwent surgery, with a hospital length of stay (LOS) ≥1 day and at least 6 months of follow-up. ASA classifications were obtained from preoperative anesthesiology notes. Preoperative CGA scores ranged from 0 to 13. Six-month survival was assessed using the Social Security Death Index. Results: In total, 81 of the 980 patients (8.3%) included in the study cohort died within 6 months of surgery. Most patients were classified as ASA PS III (85.4%). The mean number of CGA deficits for patients with PS II was 4.03, PS III was 5.15, and PS IV was 6.95 ( P &lt;.001). ASA classification was significantly associated with age, preoperative albumin level, hospital LOS, and 30-day intensive care unit (ICU) admissions. On multivariable analysis, 6-month mortality was associated with number of CGA deficits (odds ratio [OR], 1.14 per each unit increase in CGA score; P =.01), 30-day ICU admissions (OR, 2.77; P =.003), hospital LOS (OR, 1.03; P =.02), and preoperative albumin level (OR, 0.36; P =.004). ASA classification was not associated with 6-month mortality. Conclusions: Number of CGA deficits was strongly associated with 6-month mortality; ASA classification was not. Preoperative CGA elicits critical information that can be used to enhance the prediction of postoperative outcomes among older patients with cancer.
PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt
Authors: Uzodinma U. Uche, Ann R. Piccirillo, Shunsuke Kataoka, Stephanie J. Grebinoski, Louise M. D’Cruz, Lawrence P. Kane
Journal: The Journal of Experimental Medicine (2018)

Phosphatidylinositol-3 kinases (PI3Ks) modulate cellular growth, proliferation, and survival; dysregulation of the PI3K pathway can lead to autoimmune disease and cancer. PIK3IP1 (or transmembrane inhibitor of PI3K [TrIP]) is a putative transmembrane regulator of PI3K. TrIP contains an extracellular kringle domain and an intracellular domain with homology to the inter-SH2 domain of the PI3K regulatory subunit p85, but the mechanism of TrIP function is poorly understood. We show that both the kringle and p85-like domains are necessary for TrIP inhibition of PI3K and that TrIP is down-modulated from the surface of T cells during T cell activation. In addition, we present evidence that the kringle domain may modulate TrIP function by mediating oligomerization. Using an inducible knockout mouse model, we show that TrIP-deficient T cells exhibit more robust activation and can mediate clearance of Listeria monocytogenes infection faster than WT mice. Thus, TrIP is a negative regulator of T cell activation and may represent a novel target for immune modulation.
Abstract 15875: Waitlist Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the United States
Authors: Laith Alshawabkeh, Nan Hu, Knute D Carter, KellyAnn Light-McGroary, Joseph E Cavanaugh, Heather L Bartlett
Journal: Circulation (2015)

Background: Heart failure represents a final common pathway for many adult survivors with congenital heart disease (ACHD). Data assessing severity and management of heart failure are limited, and often heart transplantation is the only viable treatment option. The criteria used to determine priority status at the time of transplant listing, however, does not account for ACHD physiology. We investigated the differences in death or delisting due to clinical worsening in ACHD vs. non-ACHD candidates for heart transplantation. Methods: We conducted a retrospective study of all patients listed for heart transplantation in the United States between 1999 and 2014 using the Scientific Registry of Transplant Recipients. Patients were censored at the time of transplant or delisting due to improvement. Results: Among the 1,290 ACHD and 35,559 non-ACHD patients listed for heart transplantation, median age was 35 vs. 56 years and 62% vs. 76% were male, respectively. Waitlist outcomes for the full follow up time per initial listing status are shown in Figure 1. Of the patients who died or worsened, 57% were initially listed at the lowest priority status for ACHD compared to 40% for non-ACHD. In patients initially listed at status 1A, the 180-day actuarial probability of death or delisting due to worsening was 41% for ACHD vs. 29% for non-ACHD, p &lt; 0.01; and for death alone was 29% vs. 21%, p = 0.05; respectively, Figure 2. Conclusion: ACHD candidates for heart transplantation in the United States are more frequently listed at the lowest priority status, and when listed at the highest priority status are more likely to die or be delisted due to clinical worsening compared to other candidates.
AB1124 PREDICTIVE VALUE OF MRI FOR CT-GUIDED POSITIVE BIOPSY IN SUSPECTED INFECTIOUS SPONDYLODISCITIS
Authors: Aicha Ben Tekaya, Lobna Ben Ammar, Olfa Saidane, Rawdha Tekaya, Mohammed Ben Hammamia, Ines Mahmoud, Leila Abdelmoula
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Spondylodiscitis is a potentially life-threatening infection burdened by high morbidity rates. MRI remains the key examination in the diagnosis of infectious spondylodiscitis. The microbiological diagnosis is the main predictive factor for successful treatment. <h3>Objectives</h3> To evaluate the MRI characteristics associated with the detection of microbial pathogens by computed tomography (CT) guided biopsy in case of suspicion of infectious spondylodiscitis. <h3>Methods</h3> Retrospective study including all patients hospitalized in our department between 1999 and 2019 and who underwent MRI and CT-guided biopsy for suspicion of septic spondylodiscitis.The diagnosis was based on clinical, biological, radiological and bacteriological data. We divided the patients into two groups: patients with a non-contributory CT guided biopsy (group 1) and patients with a contributory biopsy (Group 2). <h3>Results</h3> We included 82 patients including 37 women and 45 men with a mean age of 56 years old [16 - 86]. The median delay of consultation was 3 months. Inflammatory back pain was reported in 78% of cases. Neurologic deficiency was noticed in 19.5% of cases. The lumbar spine was involved more than 50% of cases. Spinal MRI was performed to all patients and showed paravertebral abscess in 64.6%, epiduritis in 62.1%,intra-discal abscess in 3.6%, spinal cord compression 10.9%, and vertebral ostelysis in 6.09% of cases.The causative microorganism was mycobacterium tuberculosis in 53.6%, brucella in 24.3%, and pyogenic germs in 15.8% of cases. Disco vertebral biopsy was performed in 55 patients and was contributory in 45.4% of cases. The presence of spinal cord compression, intra-discal abscess and vertebral osteolysis was more frequent in group 2, but with no statistically significant difference (p = 0.65, 1 and 0.58; respectively). In addition, there was no significant difference in the presence of paravertebral abscess and epiduritis (p = 0.41 and 0.53; respectively). <h3>Conclusion</h3> Spondylodiscitis is an emergency which must be diagnosed on time to avoid life threatening complications, neurological sequelae and spinal deformities. <h3>Disclosure of Interests</h3> None declared
Nicotinic acid receptor subtypes and their ligands
Authors: Willem Soudijn, Ineke van Wijngaarden, Adriaan P. IJzerman
Journal: Medicinal Research Reviews (2007)

Abstract Half a century ago, nicotinic acid (niacin) was introduced into the clinic as the first orally available drug to treat high cholesterol levels and to improve the balance between (V)low density lipoproteins (LDL) and high density lipoproteins (HDL). Remarkably, its putative mechanism of action has only been recently elucidated, particularly because of the cloning of a G protein‐coupled receptor (HM74A or GPR109A). This receptor responds to both nicotinic acid and the ketone body β‐hydroxybutyrate, the latter thought to be the more probable endogenous ligand for HM74A. In this review, we will discuss the pharmacology and medicinal chemistry of this receptor subtype and a related one (HM74 or GPR109B). Although still in its infancy, the ligand repertoire is developing, and a number of compound classes have now been described, among which are both full and partial agonists. Antagonists, however, are still lacking, thus compromising thorough pharmacological studies. Mutagenesis experiments have provided clues regarding the ligand binding site; in particular, an arginine residue in transmembrane domain 3 of the receptor seems to recognize the acidic moiety present in nicotinic acid and related substances. HM74A has also been linked to one of the major side effects of nicotinic acid, that is, flushing, since this receptor subtype also occurs in skin immune cells. It is not known yet whether HM74 is also present on these cells. Since nicotinic acid is one of the few available medicines that raise HDL (“good cholesterol”) levels, HM74A and HM74 appear promising targets for future pharmacotherapy. © 2007 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 417–433, 2007
PS1577 PLATELET COUNT AND MEAN PLATELET VOLUME IN ACUTE STROKE: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Authors: H.A. Shemirani, F. Sadeghi, S. Kovács, K.S. Zsóri, Z. Bereczky, Z. csiki
Journal: HemaSphere (2019)

Background: Changes of platelet count (PC) and mean platelet volume (MPV) could be a marker or a predictor of acute stroke (AS). Aims: We conducted a systematic review and meta‐analysis of the published literature on the reporting of MPV and PC in AS. Methods: Medline, EBSCOhost, Web of Science, ScienceDirect, Google Scholar and Scopus were searched for studies. Studies were included in accordance with Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting (PICOS) framework. The PRISMA strategy was used to report findings. Risk of bias was assessed with Newcastle‐Ottawa Scale. The inclusion criteria were case‐control or cross‐sectional studies, individuals suffered an acute stroke, with fatal or non‐fatal stroke outcomes. Standardized mean difference (SMD) was calculated with a confidence interval of 95% (95% CI). Results: We included 32 eligible articles retrieved from the literature. PC was significantly lower in AS patients [standardized mean difference (SMD) = 0.30, (95%CI: 0.49–0.11), N = 2492, P = 0.002] compared with controls (N = 3615). The MPV was significantly higher [SMD = 0.51, (95%CI: 0.27–0.74), N = 2413, P &lt; 0.001] compared with controls (N = 3621). Subgroup analyses showed significantly lower PC in both ischemic stroke (Difference SMD = 0.18, 95%CI: 0.35‐0.01) and hemorrhagic stroke (0.94, 1.62–0.25), but only samples by citrate anticoagulant showed significantly lower result for patients compared to controls (0.36, 0.68–0.04). Ischemic stroke patients had higher MPV (0.55, 0.29–0.81), and samples by EDTA anticoagulant showed significantly higher result for patients compared to controls (0.79, 0.49–1.10). Summary/Conclusion: PC and MPV appeared to be significantly different between patients with AS and control populations. MPV was significantly higher in ischemic stroke and PC was significantly lower in both ischemic and hemorrhagic strokes. It is advisable to pay attention to the type of anticoagulant for hematology analyses in AS. Our results highlight the potential predictive role of PC and MPV in the occurrence of stroke.
PS1072 SURVIVAL OF B‐CELL LYMPHOMAS IN THE PRE‐ AND POST‐RITUXIMAB ERAS: 30 YEARS REAL‐WORLD DATA
Authors: M. Gouda
Journal: HemaSphere (2019)

Background: Rituximab is an anti‐CD20 monoclonal antibody that has been approved by FDA in 1997 for treatment of B cell lymphomas. Most data about the effect of Rituximab on survival come from either randomized controlled trials or retrospectively from local centers’ experiences. Aims: The aim of this study was to report on the real‐world experience in the United States for patients with B‐cell lymphomas using data available in the SEER (National Cancer Institute Surveillance, Epidemiology, and End Results) program's database. SEER incorporates data from 18 cancer registries all over the United States and includes data dating back to 1973. These nationwide and historical data enabled the comparison between cases diagnosed 1983–1997 (15 years before Rituximab approval) and cases diagnosed 1998–2012 (15 years after Rituximab approval). Methods: Data were obtained using SEER ∗ Stat version 8.3.5 where (SEER 18 Regs Nov 2017 Submission) database was used as the main data source. B‐cell Non‐Hodgkin lymphoma cases diagnosed between 1983 and 2012 were included. Survival analyses were made using IBM SPSS version 25.0 and SEER ∗ Stat software. Comparison between groups was done using Log‐rank test while relative survival was calculated using Ederer II method. image Results: A total number of 230577 cases were included in the analysis. B‐Cell lymphomas showed a median survival of 94 months (95% CI: 93–95) compared to 50 months (95% CI: 48.7–51.3) in the post and pre rituximab eras, respectively. Log rank test showed statstically significant difference in survival between the two groups (p &lt; 0.001) (Figure1). This difference was consistent among all stage groups (Table 1). Summary/Conclusion: Rituximab's approval has led to a dramatic improvement in survival of patients with B‐Cell lymphomas. Data from United States confirms that this improvement was consistent in all disease stages.
Abstract 255: Sex Difference of Clinical Outcomes in Patients with Out-of-Hospital Cardiopulmonary Arrest: A Prospective Multicenter Observational Study
Authors: Tomoyoshi Tamura, Noritoshi Ito, Kei Nishiyama, Kei Hayashida, Masaru Suzuki, Toshiaki Mochizuki, Atsushi Kataoka, Noriaki Yamada, Tsuyoshi Hatada, Hideo Himeno, Masayuki Fujioka, Taku Oomura, Yukitoshi Toyoda, Mitsuru Abe, Takaya Morooka, Yuusuke Taniguchi, Shingo Hori
Journal: Circulation (2013)

OBJECTIVE: There is a strong interest in differences in the outcomes between men and women with out-of-hospital cardiopulmonary arrest (OHCA). The aim of this study is to examine the sex differences of clinical outcomes in patients with OHCA. METHODS: The Japan-Prediction of neurological Outcomes in patients Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether regional cerebral oxygen saturation (rSO2) predicts neurological outcomes in OHCA. In this post-hoc analysis, OHCA were collected after excluding patients exposed to extracorporeal cardiopulmonary bypass from the J-POP registry. The primary outcome measure was a return of spontaneous circulation (ROSC) prior to hospital arrival, and secondary outcome measure was a 90-days neurological outcome. Results: Between May 2011 and July 2012, 1204 consecutive patients, age 72±15 years, 40.4% of women, were examined. Men were younger than women (70±15 vs. 75±15 years, p&lt;0.001), with higher percentage of witness status (53.7% vs. 43.1%, p&lt;0.001), and with higher percentage of rSO2 more than 40% at hospital arrival (12.1% vs. 7.0%, p&lt;0.01), and tended to have higher percentage of cardiac etiology (57.6% vs. 52.4%, p=0.07). 118 (9.8%) patients achieved ROSC prior to hospital arrival. 90-day survival rate was 6.1% (n=73), and 90-day good neurological outcome rate was 3.5% (n=42). Men had higher chance of ROSC (11.7% vs. 7.0%, p&lt;0.01), and good neurological outcome at 90 days (4.6% vs. 1.8%, p=0.01). Multivariate analysis adjusting for age (less than 75 y/o or not), witnessed, received CPR by bystander and etiology revealed that sex male was chosen as an independent predictor for ROSC prior to arrival (RR 1.59, 95%CIs 1.03-2.45). Mantel-Haenszel test adjusting for cardiac etiology also showed that men had higher rate of good neurological outcome (RR 2.47, 95%CIs 1.16-5.23). Conclusion: Our results demonstrate that men had significantly better chance of ROSC regardless of age, received BLS and etiology, and had better neurological prognosis after cardiogenic OHCA. Additional studies are needed to validate these observations for other potential genetic factors.
AB0680 NAIFOLD VIDEOCAPILLAROSCOPY PATTERN CORRELATES WITH ORGAN INVOLVEMENT AND DISEASE OUTCOME IN SYSTEMIC SCLEROSIS: A SINGLE-CENTER OBSERVATIONAL STUDY
Authors: Argyro Repa, George Bertsias, Nikolaos Kougkas, Nestor Avgustidis, Maria Terizaki, Paraskevi Kyfonidou, Prodromos Sidiropoulos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized by systemic autoimmunity, vasculopathy and fibrosis. Nailfold Videocapillaroscopy (NVC) is a safe method to detect and to analyze morphological microvascular abnormalities in SSc patients. There is circumstantial evidence to suggest an association between NVC abnormalities and disease severity, particularly vascular manifestations.<sup>1</sup> <h3>Objectives</h3> To evaluate the association of NVC patterns with demographic, clinical, laboratory features and disease progression in the SSc cohort of University Hospital of Heraklion. <h3>Methods</h3> Retrospective study (2011-2018) of SSc patients who underwent NVC. NVC findings were classified into three distinct patterns namely early, active and late according to <i>Cutolo et al<sup>2</sup></i>. NVC patterns were correlated with the clinical characteristics of the patients. We also correlated baseline NVC patterns with the progression of the disease at 3 years. <h3>Results</h3> 62 patients [(88.8% women, mean age of diagnosis 49.8 years, range 18-82)] were included. Compared to early/active pattern, patients with late pattern were more likely to have diffuse SSc (dSSc) (p=0.006), interstitial Lung Disease (ILD) (80.0% vs 38.1% p=0.002) and esophageal involvement (80.0% vs 47.6% p=0.0034). There was a trend for increased frequency of Pulmonary arterial Hypertension (PAH), digital ulcers (DU) and calcinosis in patients with late pattern (p=0.079, p=1.103 and p=0.079 respectively). Patients with active NVC pattern were more likely to have arthritis (early/active/late: 36.4%/75.9%/55.0%, p=0.054). A total 42 patients had NVC data at the time of SSc diagnosis. At 3 years there were no significant differences regarding disease progression, although patients with late NVC pattern had more hospitalizations due to infections (33.3% vs 9.1%, p=0.191), higher death rate (16.7% vs. 8.3%, p=0.543), need to use cyclophosphamide (33.3% vs 17.4%, p=0.391) and/or bosentan (40.0% vs 22.7%, p=0.426). <h3>Conclusion</h3> In this single-center SSc cohort, NVC pattern was found to correlate with organ involvement especially ILD, esophageal involvement and dSSc. Serious infections and treatment intensification were also more frequent among patients with late NVC pattern. NVC may be a useful prognostic marker for SSc patients. <h3>References</h3> [1] Paxton Det al, Semin arthritis Rheum. 2018Dec;48(3):482-494 [2] Cutolo M, et al. Assessing microvascular changes in systemic sclerosis diagnosis and management, Nat Rev Rheumatol. 2010 <h3>Acknowledgement</h3> This study was funded by Hellenic Society of Rheumatology &amp; Professionals Union of Rheumatologists of Greece <h3>Disclosure of interests</h3> None declared
Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity
Authors: Annelise G. Snyder, Nicholas W. Hubbard, Michelle N. Messmer, Sigal B. Kofman, Cassidy E. Hagan, Susana L. Orozco, Kristy Chiang, Brian P. Daniels, David Baker, Andrew Oberst
Journal: Science Immunology (2019)

Although the signaling events that induce different forms of programmed cell death are well defined, the subsequent immune responses to dying cells in the context of cancer remain relatively unexplored. Necroptosis occurs downstream of the receptor-interacting protein kinases RIPK1 and RIPK3, whose activation leads to lytic cell death accompanied by de novo production of proinflammatory mediators. Here, we show that ectopic introduction of necroptotic cells to the tumor microenvironment promotes BATF3+ cDC1- and CD8+ leukocyte-dependent antitumor immunity accompanied by increased tumor antigen loading by tumor-associated antigen-presenting cells. Furthermore, we report the development of constitutively active forms of the necroptosis-inducing enzyme RIPK3 and show that delivery of a gene encoding this enzyme to tumor cells using adeno-associated viruses induces tumor cell necroptosis, which synergizes with immune checkpoint blockade to promote durable tumor clearance. These findings support a role for RIPK1/RIPK3 activation as a beneficial proximal target in the initiation of tumor immunity. Considering that successful tumor immunotherapy regimens will require the rational application of multiple treatment modalities, we propose that maximizing the immunogenicity of dying cells within the tumor microenvironment through specific activation of the necroptotic pathway represents a beneficial treatment approach that may warrant further clinical development.
PF703 LONG‐TERM FOSTAMATINIB TREATMENT OF ADULTS WITH IMMUNE THROMBOCYTOPENIA (ITP) DURING THE PHASE 3 CLINICAL TRIAL PROGRAM
Authors: J. Bussel, D. Arnold, R. Boccia, M. Boxer, N. Cooper, Q. Hill, D. Liles, M. Scholzberg, R. Numerof, H. Zayed, S. Tong, A.‐M. Duliege
Journal: HemaSphere (2019)

Background: Fostamatinib (Tavalisse ® ), an oral SYK inhibitor was approved in 2018 for the treatment of adults with chronic ITP who had an insufficient response to a prior treatment. In two randomized, double‐blind studies, 102 patients received fostamatinib and 48 received placebo; in the open‐label extension study, 123 received fostamatinib, including 44 from the placebo group. Aims: This abstract provides an update on 146 patients who have had up to 3 years of fostamatinib treatment. Methods: Adults with persistent/chronic ITP who had failed ≥1 prior therapy and had ≥3 platelet counts &lt;30,000/μL at screening, were treated with fostamatinib at 100 mg BID, which increased to 150 mg BID based on tolerability, if platelets were &lt;50,000/μL after 1 month. An overall response (post‐hoc analysis) was defined as achieving ≥1 platelet count of ≥50,000/μL within the first 12 weeks of treatment. Analyses excluded counts within 4 weeks of rescue therapy. Results: At the time of analysis, 42 (29%) of the 146 patients who received fostamatinib were continuing treatment. Reasons for treatment discontinuation included lack of response (41%), adverse events (AEs) (18%) and other (12%). An overall response occurred in 64/146 (44%) patients. Responders had reduced need for rescue medications and fewer bleeding episodes. The median platelet count in overall responders remained above 50,000/μL for more than 36 months. The most common AEs were diarrhea, hypertension and nausea, which were manageable with targeted treatment, dose modifications, or treatment withdrawal. Serious adverse events (SAE) were reported in 27% of patients and were possibly related to fostamatinib in 6%. SAEs led to treatment discontinuation in 3% of patients. Summary/Conclusion: 44% of patients had an overall response to fostamatinib. Fostamatinib was well tolerated for an extended period of time. No new safety signals and no cumulative toxicity was detected during long‐term treatment with fostamatinib (up to 41 months). image