tbuckley/cabot-search huggingface dataset:
SAT0240 THE PROGNOSIS OF TWO DISTINCT CLINICAL PHENOTYPES OF SLE-PAH
Authors: J. Wang, Y. Feng, Y. Lei, X. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Based on the characteristics of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH), Sun et al has put forward a scoring system to distinguish two clinical phenotypes as vasculitic and vasculopathic subtypes[1]. A weighted score ≥2 suggested a vasculitic subtype by combining two factors: The time interval between SLE and PAH diagnosis &lt;2 years and ≥2 years were 1 and 0 point; SLE Disease Activity Index (SLEDAI) &gt;9, 5-9 and &lt;5 were 2, 1, 0 point, respectively. While the vasculitic subtype seemed to have poorer prognosis in Sun’s research, other study has shown controversial result[2]. Objectives: To find out the prognosis of two distinct clinical phenotypes of SLE-PAH. Methods: Between 2008 and 2019, a SLE-PAH cohort confirmed by right heart catheterization (RHC) from Guangdong Provincial People’s Hospital was included. Other groups of pulmonary hypertension were excluded. Based on the scoring system, patients were divided into vasculitic (weighted score≥2) and vasculopathic subtypes (weighted score&lt;2). The endpoint was PAH-related mortality. Survival status were confirmed by clinic follow-up data or phone call. Results: A total of 53 SLE-PAH patients were enrolled. The cases of vasculitic and vasculopathic subtype were 14 and 39, respectively. Ten endpoint events occurred. Eight attributed to PAH and the cause could not be traced in two which were still included in study. The pooled 1-, 3-, 5-year survival rates were 85.7%, 78.6%, 65.5% in vasculitic subtype, and 93.9%, 87.5%, 87.5% in vasculopathic subtype, respectively. Kaplan-Meier analysis showed vasculitic subtype tended to have a poorer prognosis than vasculopathic subtype ( p =0.16, HR 2.4, 95%CI 0.5-13.8, figure 1). Figure 1. Survival curves for patients with systemic lupus erythematosus-pulmonary arterial hypertension (SLE-PAH) in two distinct subtypes. RHC, Right Heart Catheterization. Conclusion: The prognosis of the two phenotypes of SLE-PAH was statistically indifferent while the vasculitic subtype showed a trend of worse prognosis. Further studies are needed. References: [1]F. Sun, Y. Lei, W. Wu, L. Guo, K. Wang, Z. Chen, W. Xu, X. Wang, T. Li, X. Zhang, S. Ye, Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to systemic lupus erythematosus, Ann Rheum Dis 78(1) (2019) 148-150. [2]J. Qian, M. Li, J. Zhao, Q. Wang, Z. Tian, X. Zeng, Inflammation in SLE-PAH: good news or not?, Ann Rheum Dis (2018). 0 :1–2. doi:10.1136/annrheumdis-2018-214605 Disclosure of Interests: None declared
Optimizing the Gold Standard—Low-Dose Computed Tomography Modalities as a Part of Clinical Practice in Acute Appendicitis Imaging
Authors: Jussi Haijanen, Sami Sula, Paulina Salminen
Journal: JAMA Surgery (2021)

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Open letter to Chris Whitty and Susan Hopkins: change covid-19 case definition in line with WHO to save lives
Authors: Alex Sohal
Journal: BMJ (2021)

<h3>BACKGROUND AND PURPOSE:</h3> Dynamic contrast-enhanced MR imaging parameters can be biased by poor measurement of the vascular input function. We have compared the diagnostic accuracy of dynamic contrast-enhanced MR imaging by using a phase-derived vascular input function and “bookend” T1 measurements with DSC MR imaging for preoperative grading of astrocytomas. <h3>MATERIALS AND METHODS:</h3> This prospective study included 48 patients with a new pathologic diagnosis of an astrocytoma. Preoperative MR imaging was performed at 3T, which included 2 injections of 5-mL gadobutrol for dynamic contrast-enhanced and DSC MR imaging. During dynamic contrast-enhanced MR imaging, both magnitude and phase images were acquired to estimate plasma volume obtained from phase-derived vascular input function (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function (<i>K</i><sup>trans</sup>_Φ) as well as plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (<i>K</i><sup>trans</sup>_SI). From DSC MR imaging, corrected relative CBV was computed. Four ROIs were placed over the solid part of the tumor, and the highest value among the ROIs was recorded. A Mann-Whitney <i>U</i> test was used to test for difference between grades. Diagnostic accuracy was assessed by using receiver operating characteristic analysis. <h3>RESULTS:</h3> Vp_ Φ and <i>K</i><sup>trans</sup>_Φ values were lower for grade II compared with grade III astrocytomas (<i>P</i> &lt; .05). Vp_SI and <i>K</i><sup>trans</sup>_SI were not significantly different between grade II and grade III astrocytomas (<i>P</i> = .08–0.15). Relative CBV and dynamic contrast-enhanced MR imaging parameters except for <i>K</i><sup>trans</sup>_SI were lower for grade III compared with grade IV (<i>P</i> ≤ .05). In differentiating low- and high-grade astrocytomas, we found no statistically significant difference in diagnostic accuracy between relative CBV and dynamic contrast-enhanced MR imaging parameters. <h3>CONCLUSIONS:</h3> In the preoperative grading of astrocytomas, the diagnostic accuracy of dynamic contrast-enhanced MR imaging parameters is similar to that of relative CBV.
Clinician perspectives on preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies.
Authors: Kelsey S. Lau-Min, Lisa A. Varughese, Maria N. Nelson, Christine Cambareri, Nandi J. Reddy, Randall A. Oyer, Ursina R. Teitelbaum, Sony Tuteja
Journal: Journal of Clinical Oncology (2021)

54 Background: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods: We conducted a multi-site mixed-methods study to understand clinician attitudes toward PGx testing and to identify facilitators and barriers to using preemptive testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a demographic survey and semi-structured interview informed by the Consolidated Framework for Implementation Research. Interviews were analyzed using a modified grounded theory approach. Results: A total of 16 medical oncologists and 9 oncology pharmacists from one academic medical center and two community hospitals participated. Fifteen (60%) participants reported feeling comfortable or very comfortable with interpreting PGx test results. While clinicians expressed generally favorable attitudes toward PGx testing, many were hesitant to use it to preemptively guide chemotherapy dosing due to a perceived lack of evidence for this practice. They cited a lack of consensus chemotherapy dosing recommendations in response to PGx test results, as well as concerns about decreased drug efficacy, especially in patients treated with curative intent. Additional barriers included 1) a low prevalence of actionable PGx variants; 2) lengthy PGx test turnaround time; 3) concerns about testing costs and lack of insurance coverage; and 4) burdensome integration of PGx testing into clinical workflows. The electronic health record emerged as a potential tool for the unobtrusive integration of PGx testing into clinical practice–suggested applications included default PGx test orders for eligible patients, discrete reporting of PGx variant results, and clinical decision support to guide subsequent chemotherapy dosing. Conclusions: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multi-level effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study. The electronic health record should be explored as a tool to integrate PGx testing into routine practice.
DEDUCTIVE: A study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma—Phase Ib results.
Authors: Renuka V. Iyer, Daneng Li, Farshid Dayyani, Alexandria T. Phan, Michael N. Needle, Thomas Adam Abrams
Journal: Journal of Clinical Oncology (2021)

294 Background: A recent ph3 study combining bevacizumab (VEGF-A Mab) with atezolizumab (PD-L1 inhibitor) has shown significant improvements in OS and PFS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over sorafenib. Tivozanib (T, a potent and selective VEGFR 1, 2 &amp; 3 TKI) and durvalumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies. T blocks all three VEGF receptors, and when combined with a PD-L1 inhibitor may improve patient outcomes. The ph1 portion of this study combines T with D to establish the recommended phase II dose (RP2D) and provide preliminary safety and efficacy data. Methods: Major eligibility criteria are adults with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance &gt; 40 ml/min. Major exclusion criteria are co-infection with HBV and HCV and significant organ dysfunction. The starting dose is the combination of T 1 mg orally for 21 days followed by 7 days off treatment and D 1500 mg intravenously every 28 days. A DLT is generally defined as the occurrence of any Grade ≥3 immune or non-immune adverse event (AE) in Cycle 1 that is at least possibly related to the investigational regimen other than any grade of vitiligo or alopecia or Grade 3 controllable hypertension in cycle 1. The primary objective is to establish the RP2D and the safety and tolerability for this combination in patients with advanced HCC. Patients will be treated until progression of disease, unacceptable side effects, or death. Outcome measures will be AEs per CTCAE v.5 and cross-sectional imaging performed every 8 weeks. Results: Seven patients were enrolled in phase I. Six were male; the median age was 75 (range 40 to 82). One patient had mild elevation of LFTs and did not complete the 21-day course of T and was replaced. No patient experienced a &gt;=grade 3 AE in cycle 1. The most common AEs, each seen in two of seven patients, were anorexia, cough, diarrhea, dysphonia, fatigue, hypertension, and palmar-plantar erythrodysesthesia. Two of seven have achieved a partial response. Conclusions: The combination of T with D in patients with untreated advanced HCC is well tolerated. The RP2D for the combination is T 1 mg orally for 21 days on treatment followed by 7 days off treatment and D 1500 mg intravenously every 28 days. In the phase II portion of the study an additional 30 patients will be treated at the RP2D. Secondary objectives are to assess the objective response rate, progression free survival, and overall survival in this population. Clinical trial information: NCT03970616.
Response to a COVID-19 Outbreak on a University Campus — Indiana, August 2020
Authors: Mark D. Fox, David C. Bailey, Michael D. Seamon, Marie Lynn Miranda
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Institutions of higher education adopted different approaches for the fall semester 2020 in response to the coronavirus disease 2019 pandemic.Approximately 45% of colleges and universities implemented online instruction, more than one fourth (27%) provided in-person instruction, and 21% used a hybrid model (1).Although CDC has published COVID-19 guidance for institutions of higher education (2-4), little has been published regarding the response to COVID-19 outbreaks on college and university campuses (5).In August 2020, an Indiana university with approximately 12,000 students (including 8,000 undergraduate students, 85% of whom lived on campus) implemented various public health measures to reduce transmission of SARS-CoV-2, the virus that causes COVID-19.Despite these measures, the university experienced an outbreak involving 371 cases during the first few weeks of the fall semester.The majority of cases occurred among undergraduate students living off campus, and several large off-campus gatherings were identified as common sources of exposure.Rather than sending students home, the university switched from in-person to online instruction for undergraduate students and instituted a series of campus restrictions for 2 weeks, during which testing, contact tracing, and isolation and quarantine programs were substantially enhanced, along with educational efforts highlighting the need for strict adherence to the mitigation measures.After 2 weeks, the university implemented a phased return to in-person instruction (with 85% of classes offered in person) and resumption of student life activities.This report describes the outbreak and the data-driven, targeted interventions and rapid escalation of testing, tracing, and isolation measures that enabled the medium-sized university to resume in-person instruction and campus activities.These strategies might prove useful to other colleges and universities responding to campus outbreaks.
FRI0138 Anticardiolipin antibody isotype profile and lupus nephritis severity based on renal biopsy pathology
Authors: JC Tseng, CC Chiu, CM Hsu, RJ Hu, LY Lu, HH Cheng
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Lupus nephritis remains the most prominent organ system manifestation of systemic lupus erythematosus (SLE) and is associated with high morbidity and mortality, particularly in the diffuse proliferative form of the World Health Organisation classification. Evidences have shown that antiphospholipid antibodies may be of pathogenetic significance in lupus nephritis, since glomerular capillary thrombi are an indicator of subsequent renal dysfunction. <h3>Objectives</h3> To determine anticardiolipin antibody isotype profile in SLE patients with and without lupus nephritis, and the association with lupus nephritis severity based on renal biopsy classification. <h3>Methods</h3> 200 Chinese SLE patients, followed between Jan. 1991 to May 1996 at Kaohsiung Veterans General Hospital Rheumatology Clinic were included in this study. All patients fulfilled ARA criteria for SLE. Anticardiolipin antibody (aCL) was measured by the ELISA according to international standardised method in 100 SLE patients with lupus nephritis verified by renal biopsy (Group A), 100 SLE patients without lupus nephritis (Group B), and 30 patients with renal biopsy-proved nephropathy not due to SLE (Group C). Renal biopsy morphology was assessed using WHO criteria for the classification of lupus nephritis. aCL isotype profile was analysed in each group and in the subgroups of lupus nephritis patients according to WHO classification. <h3>Results</h3> <h3>Conclusion</h3> In this study, the frequency of aCL in our SLE patients was low as compared to previous reports. It may be due to racial difference. From our preliminary data, though not statistically significant, no difference in the frequency of aCL was identified amongst patients with and without lupus nephritis. No correlation between aCL isotype profile and the severity of lupus nephritis could be demonstrated.
Lung clearance index predicts pulmonary exacerbations in individuals with primary ciliary dyskinesia: a multicentre cohort study
Authors: Florian Singer, Anne Schlegtendal, Sylvia Nyilas, François Vermeulen, Mieke Boon, Cordula Koerner-Rettberg
Journal: Thorax (2021)

Background Lung clearance index (LCI) is a promising lung function outcome in individuals with primary ciliary dyskinesia (PCD). The impact of events clinically important for individuals with PCD, such as pulmonary exacerbations, on LCI is unknown. Methods We conducted an international, multicentre, observational cohort study to assess the association of LCI and risk of pulmonary exacerbation, specific changes in LCI during pulmonary exacerbation and global variability of LCI across four visits every 4 months. Ninety individuals with PCD, aged 3–41 years, underwent nitrogen multiple-breath washout (MBW) and spirometry measurements. The association of LCI and pulmonary exacerbations was assessed by Cox proportional hazards and random-effects regression models. Results We obtained 430 MBW and 427 spirometry measurements. In total, 379 person-years at risk contributed to the analysis. Per one unit increase (deterioration) in LCI, the risk of future pulmonary exacerbation increased by 13%: HR (95% CI), 1.13 (1.04 to 1.23). If LCI changed from a range of values considered normal to abnormal, the risk of future pulmonary exacerbations increased by 87%: 1.87 (1.08 to 3.23). During pulmonary exacerbations, LCI increased by 1.22 units (14.5%). After pulmonary exacerbations, LCI tended to decline. Estimates of variability in LCI suggested lower variation within individuals compared with variation between individuals. Findings were comparable for forced expiratory volume in 1 s. Conclusion On a visit-to-visit basis, LCI measurement may add to the prediction of pulmonary exacerbations, the assessment of lung function decline and the potential lung function response to treatment of pulmonary exacerbations.
THU0166 High diagnostic value of anti-filaggrin autoantibodies (afa) detected by a new elisa in a cohort of 152 community cases of very early arthritis
Authors: O Vittecoq, B Inçaurgarat, J Legoedec, A Gayet, P Fardellone, P Boumier, A Phan Van, JM Bertho, C Zarnitsky, O Mejjad, A Daragon, M Jolivet, F Tron, X Le Loët
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the diagnostic value of autoantibodies (Ab) directed against citrullinated recombinant rat filaggrin (ACRFA) for very early RA. <h3>Methods</h3> From a population-based recruitment, 152 patients with early (median disease duration:4 months [2‑6 mo]) peripheral arthritis (swelling of at least 2 joints persisting &gt; 4 weeks) were studied. Follow-up period was 1 year. At the end of the study, patients were classified as RA (n = 88) or as other rheumatic diseases. Four Ab: rheumatoid factors (RF-IgM), anti-keratin Ab (AKA), anti-perinuclear factor (APF) and ACRFA by an ELISA whose result are expressed as the difference of OD values given by sera tested against the citrullinated and non-citrullinated forms of filaggrin were tested at entry. <h3>Results</h3> Characteristics of these markers for RA are reported in the Table 1. Specificity of ACRFA was better than that of RF, APF and to a lesser degree AKA. Sensitivity of ACRFA was higher than that of AKA which is the single test still routinely used for detection of AFA. AKA, APF and ACRFA were complementary since certain sera were positive for only one test. Only 5/48 (10.5%) RF-negative RA patients were positive for ACRFA. <h3>Conclusion</h3> AFA detected by a new ELISA have a higher diagnostic value for RA than AFA identified by previous tests in this population-based cohort of very early arthritis. Study granted by the Fondation de la Recherche Médicale (FRM), the Association de Recherche sur la Polyarthrite (ARP) and for clinical assessment Pharmacia-Searle, France.
ER-to-Golgi transport and SEC23-dependent COPII vesicles regulate T cell alloimmunity
Authors: Stephanie Kim, Rami Khoriaty, Lu Li, Madison McClune, Theodosia A. Kalfa, Julia Wu, Daniel Peltier, Hideaki Fujiwara, Yaping Sun, Katherine Oravecz-Wilson, Richard A. King, David Ginsburg, Pavan Reddy
Journal: Journal of Clinical Investigation (2021)

T cell–mediated responses are dependent on their secretion of key effector molecules. However, the critical molecular determinants of the secretion of these proteins are largely undefined. Here, we demonstrate that T cell activation increases trafficking via the ER-to-Golgi pathway. To study the functional role of this pathway, we generated mice with a T cell–specific deletion in SEC23B, a core subunit of coat protein complex II (COPII). We found that SEC23B critically regulated the T cell secretome following activation. SEC23B-deficient T cells exhibited a proliferative defect and reduced effector functions in vitro, as well as in experimental models of allogeneic and xenogeneic hematopoietic cell transplantation in vivo. However, T cells derived from 3 patients with congenital dyserythropoietic anemia II (CDAII), which results from Sec23b mutation, did not exhibit a similar phenotype. Mechanistic studies demonstrated that unlike murine KO T cells, T cells from patients with CDAII harbor increased levels of the closely related paralog, SEC23A. In vivo rescue of murine KO by expression of Sec23a from the Sec23b genomic locus restored T cell functions. Together, our data demonstrate a critical role for the COPII pathway, with evidence for functional overlap in vivo between SEC23 paralogs in the regulation of T cell immunity in both mice and humans.
In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell: Erratum
Authors: Kuan Hu, Feng Yin, Mengyin Yu, Chengjie Sun, Jingxu Li, Yujie Liang, Wenjun Li, Mingsheng Xie, Yuanzhi Lao, Wei Liang, Zi-gang Li
Journal: Theranostics (2018)

[This corrects the article DOI: 10.7150/thno.19840.].
Abstract 12422: Mild Therapeutic Hypothermia Can Extend the Stemi First Medical Contact to Reperfusion Time Without Increasing Myocardial Infarct Size
Authors: Madhan Shanmugasundaram, David Ho, Arielle Tran, Alex Cavalcante, Nicole Smith, Huu Tam Truong, Karl B Kern
Journal: Circulation (2018)

Background: Primary percutaneous coronary intervention (PPCI) is the preferred treatment for acute ST segment elevation myocardial infarction (STEMI). The goal is reperfusion within 90 minutes of f...
Abstract 16536: Implementation Of Flag, Identify, Network, Deliver: Find FH Using The Electronic Medical Record To Identify Familial Hypercholesterolemia Within A Single Healthcare System
Authors: Samip Sheth, Latoya Williamson, Jinbo Chen, David Staszak, Gayley Webb, Marjorie Risman, Yuliya Borovskiy, Erik Hossain, Jihane Hajj, Kady Diu, Julia A Larsen, Jennifer Boring, Cynthia Mays, William Howard, Dave Zuzick, Archna Bajaj, Daniel E Soffer, Marina Cuchel, Samuel Gidding, Katherine A Wilemon, Daniel J Rader, Kelly Myers, Douglas Jacoby
Journal: Circulation (2019)

Introduction: Familial hypercholesterolemia (FH) is a common underdiagnosed and undertreated condition that leads to premature cardiovascular disease. The FH Foundation developed a machine learning...