tbuckley/cabot-search huggingface dataset:
Use of Electronic Medical Records to Estimate Changes in Pregnancy and Birth Rates During the COVID-19 Pandemic
Authors: Molly J. Stout, Cosmas J. M. Van De Ven, Vikas I. Parekh, Jennifer L. Pardo, Maxim Garifullin, Min Xu, Dee E. Fenner, Roger D. Smith
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The influence of the COVID-19 pandemic on fertility rates has been suggested in the lay press and anticipated based on documented decreases in fertility and pregnancy rates during previous major societal and economic shifts. Anticipatory planning for birth rates is important for health care systems and government agencies to accurately estimate size of economy and model working and/or aging populations. <h3>Objective</h3> To use projection modeling based on electronic health care records in a large US university medical center to estimate changes in pregnancy and birth rates prior to and after the COVID-19 pandemic societal lockdowns. <h3>Design, Setting, and Participants</h3> This cohort study included all pregnancy episodes within a single US academic health care system retrospectively from 2017 and modeled prospectively to 2021. Data were analyzed September 2021. <h3>Exposures</h3> Pre– and post–COVID-19 pandemic societal shutdown measures. <h3>Main Outcomes and Measures</h3> The primary outcome was number of new pregnancy episodes initiated within the health care system and use of those episodes to project birth volumes. Interrupted time series analysis was used to assess the degree to which COVID-19 societal changes may have factored into pregnancy episode volume. Potential reasons for the changes in volumes were compared with historical pregnancy volumes, including delays in starting prenatal care, interruptions in reproductive endocrinology and infertility services, and preterm birth rates. <h3>Results</h3> This cohort study documented a steadily increasing number of pregnancy episodes over the study period, from 4100 pregnancies in 2017 to 4620 in 2020 (28 284 total pregnancies; median maternal [interquartile range] age, 30 [27-34] years; 18 728 [66.2%] White women, 3794 [13.4%] Black women; 2177 [7.7%] Asian women). A 14% reduction in pregnancy episode initiation was observed after the societal shutdown of the COVID-19 pandemic (risk ratio, 0.86; 95% CI, 0.79-0.92;<i>P</i> &lt; .001). This decrease appeared to be due to a decrease in conceptions that followed the March 15 mandated COVID-19 pandemic societal shutdown. Prospective modeling of pregnancies currently suggests that a birth volume surge can be anticipated in summer 2021. <h3>Conclusions and Relevance</h3> This cohort study using electronic medical record surveillance found an initial decline in births associated with the COVID-19 pandemic societal changes and an anticipated increase in birth volume. Future studies can further explore how pregnancy episode volume changes can be monitored and birth rates projected in real-time during major societal events.
Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer
Authors: Jun Yin, Romain Cohen, Zhaohui Jin, Heshan Liu, Levi Pederson, Richard Adams, Axel Grothey, Timothy S Maughan, Alan Venook, Eric Van Cutsem, Cornelis Punt, Miriam Koopman, Alfredo Falcone, Niall C Tebbutt, Matthew T Seymour, Carsten Bokemeyer, Eduardo Diaz Rubio, Richard Kaplan, Volker Heinemann, Benoist Chibaudel, Takayuki Yoshino, John Zalcberg, Thierry Andre, Aimery De Gramont, Qian Shi, Heinz-Josef Lenz
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. Methods PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided. Results Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P &amp;lt; .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P &amp;lt; .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction &amp;lt; .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P &amp;lt; .001) but not for right-sidedness. Conclusions The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.
Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats
Authors: Hongyu Sun, Siyu He, Li Wu, Zeying Cao, Xian Sun, Mingwei Xu, Shan Lu, Mingdi Xu, Baoming Ning, Huimin Sun, Tiqiao Xiao, Peter York, Xu Xu, Xianzhen Yin, Jiwen Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
AB0262 CLINICAL EFFICACY OF SWITCHING FROM ORAL TO SUBCUTANEOUS METHOTREXATE IN MANAGEMENT OF RHEUMATOID ARTHRITIS: EXPERIENCE FROM OUT-PATIENT SETTING OF A DISTRICT GENERAL HOSPITAL IN UK
Authors: G. Ansari, A. Nandagudi, A. Bharadwaj
Journal: Annals of the Rheumatic Diseases (2021)

Background: Methotrexate (MTX) is an anchor drug in the treatment of Rheumatoid arthritis. The literature review has shown that subcutaneous (SC) methotrexate has shown better efficacy, less adverse side effects and better compliance in inflammatory arthritis. Our department modified Inflammatory arthritis pathway in 2018 where all patient with moderate or severe disease are switched from oral to SC Methotrexate injection for improved management. Objectives: The aim of our study is to review whether switching of oral methotrexate (PO MTX) to subcutaneous methotrexate (SC MTX) helps to improve disease activity in patients with rheumatoid arthritis and avoids the need to introduce biologic therapy. Methods: We conducted a retrospective audit of patients with rheumatoid arthritis seen between January 2018 to January 2020 recording their age, gender, diagnosis, date of MTX switch and disease activity score 6 months after switching to SC MTX. Significance of change was calculated with test of proportion/chi square test. Results: Fifty patients were reviewed, thirty eight (76%) were female and twelve (24%) were male with age ranging between 34 - 86 years (median 61.5 years). Switching to MTX injection was done within 2 yrs of diagnosis in 21 (42%) patients, between 2-5 yrs of diagnosis in 11 (22%) patients and more than 5 yrs after diagnosis in 18 (36%) patients. The main reasons of switching were either maximum MTX dose (25mg) or intolerance to oral MTX at any dose. After switching methotrexate, review at 6 months showed 26 patients (52%) in remission (compared to 6 at baseline) and 3 (6%) patients avoided the need to go on biologic therapy. Five patient commenced on biologic therapy between 3 and 6 months. Table 1. Disease activity compared at Baseline and at 6 months Disease Activity Baseline At 6 months Remission &lt;2.6 6 26 (p&lt;0.0001) Mild (26-3.19) 11 10 Mod (3.2 - 5.09) 25 9 (p&lt;0.01) Severe (&gt;5.1) 8 5 Conclusion: Switching to SC Methotrexate even in patients with long duration of disease results in significant number of patients achieving remission or lower disease activity (P&lt;0.001). This may obviate the need of biologics therapy Disclosure of Interests: None declared
POS1280 SPINAL LOCATION OF TUBERCULOSIS: WHAT HAS CHANGED OVER THE LAST YEARS?
Authors: S. Boussaid, M. Mrabet, S. Jemmali, H. Sahli, H. Ajlani, E. Cheour, S. Rekik, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2021)

Background: Tuberculosis (TB) is no longer a disease limited to developing nations and is still a major cause of significant morbidity and mortality worldwide. It can affect the different parts of the spine. Objectives: The aim of this study was to determine the preferred spinal location of TB. Methods: We conduct a retrospective and descriptive study in a single rheumatology department. Data were collected from observations of patients hospitalized in the past 20 years (2000-2020) who have been diagnosed with tuberculous spondylodiscitis (TS). Results: Fifty-two patients were included (37F/15M). Their mean age was 55.21 years ± 17.79 [19-91]. TS was more frequently unifocal (75%) than multifocal (25%). Lumbar spine involvement was the most common (57.7%) and more frequent in women (63.3%) but with no statistically significant difference (p = 0.2). Other localizations were described such as: dorso-lumbar (21.2%), dorsal (15.4%), lumbosacral (3.8%) and cervical (1.9%). Lumbar pain was present in 34 patients (65.4%) and 29 patients (55.8%) suffered from segmental lumbar stiffness. Imaging was contributive by showing the vertebral location using standard X-rays, computed tomography and magnetic resonance imaging. Disc pinch, erosion of vertebral plateaus and vertebral collapse were the major signs (82.7%, 65.4% and 67.3%, respectively). Conclusion: TS is a rare but serious clinical condition which may lead to severe deformity and early or late neurological complications. Spinal involvement is often unifocal and mostly diagnosed with lumbar pain or stiffness. Multifocal forms, touching several parts of the spine, however remain rare. Our findings remain consistent with those of the literature. Disclosure of Interests: None declared
Free, At-Home Rapid SARS-CoV-2 Tests
Authors: Rita Rubin
Journal: JAMA (2021)

The National Institutes of Health and the Centers for Disease Control and Prevention recently began offering a month's worth of free, do-it-yourself (DIY), rapid SARS-CoV-2 tests to residents of Pitt County, North Carolina, and Chattanooga/Hamilton County, Tennessee.
Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection and hospitalisation, Navarre, Spain, January to April 2021
Authors: Iván Martínez-Baz, Ana Miqueleiz, Itziar Casado, Ana Navascués, Camino Trobajo-Sanmartín, Cristina Burgui, Marcela Guevara, Carmen Ezpeleta, Jesús Castilla
Journal: Eurosurveillance (2021)

COVID-19 vaccine effectiveness was evaluated in close contacts of cases diagnosed during January–April 2021. Among 20,961 contacts, 7,240 SARS-CoV-2 infections were confirmed, with 5,467 being symptomatic and 559 leading to hospitalisations. Non-brand-specific one and two dose vaccine effectiveness were respectively, 35% (95% confidence interval (CI): 25 to 44) and 66% (95% CI: 57 to 74) against infections, 42% (95% CI: 31 to 52) and 82% (95% CI: 74 to 88) against symptomatic infection, and 72% (95% CI: 47 to 85) and 95% (95% CI: 62 to 99) against COVID-19 hospitalisation. The second dose significantly increased effectiveness. Findings support continuing complete vaccination.
BTK inhibitors, irrespective of ITK inhibition, increase efficacy of a CD19/CD3-bispecific antibody in CLL
Authors: Maissa Mhibik, Erika M. Gaglione, David Eik, Ellen K. Kendall, Amy Blackburn, Keyvan Keyvanfar, Maria Joao Baptista, Inhye E. Ahn, Clare Sun, Junpeng Qi, Christoph Rader, Adrian Wiestner
Journal: Blood (2021)
Patient-Derived Xenograft Engraftment and Breast Cancer Outcomes in a Prospective Neoadjuvant Study (BEAUTY)
Authors: Judy C. Boughey, Vera J. Suman, Jia Yu, Katelyn Santo, Jason P. Sinnwell, Jodi M. Carter, Krishna R. Kalari, Xiaojia Tang, Sarah A. McLaughlin, Alvaro Moreno-Aspitia, Donald W. Northfelt, Richard J. Gray, Katie N. Hunt, Amy Lynn Conners, James N. Ingle, Ann Moyer, Richard Weinshilboum, John A. Copland, Liewei Wang, Matthew P. Goetz
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Patient-derived xenografts (PDX) are a research tool for studying cancer biology and drug response phenotypes. While engraftment rates are higher for tumors with more aggressive characteristics, it is uncertain whether engraftment is prognostic for cancer recurrence. Patients and Methods: In a prospective study of patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with taxane ± trastuzumab followed by anthracycline-based chemotherapy, we report the association between breast cancer events and PDX engraftment using tumors derived from treatment naïve (pre-NAC biopsies from 113 patients) and treatment resistant (post-NAC at surgery from 34 patients). Gray test was used to assess whether the cumulative incidence of a breast cancer event differs with respect to either pre-NAC PDX engraftment or post-NAC PDX engraftment. Results: With a median follow-up of 5.7 years, the cumulative incidence of breast cancer relapse did not differ significantly according to pre-NAC PDX engraftment (5-year rate: 13.6% vs. 13.4%; P = 0.89). However, the incidence of a breast event was greater for patients with post-NAC PDX engraftment (5-year rate: 50.0% vs. 19.6%), but this did not achieve significance (P = 0.11). Conclusions: In treatment-naïve breast cancer receiving standard NAC, PDX engraftment was not prognostic for breast cancer recurrence. Further study is needed to establish whether PDX engraftment in the treatment-resistant setting is prognostic for cancer recurrence.
Generation and characterization of HLA-A2 transgenic mice expressing the human TCR 1G4 specific for the HLA-A2 restricted NY-ESO-1<sub>157-165</sub>tumor-specific peptide
Authors: Eugene Shenderov, Matheswaran Kandasamy, Uzi Gileadi, Jili Chen, Dawn Shepherd, James Gibbs, Gennaro Prota, Jonathan D Silk, Jonathan W Yewdell, Vincenzo Cerundolo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background NY-ESO-1 is a tumor-specific, highly immunogenic, human germ cell antigen of the MAGE-1 family that is a promising vaccine and cell therapy candidate in clinical trial development. The mouse genome does not encode an NY-ESO-1 homolog thereby not subjecting transgenic T-cells to thymic tolerance mechanisms that might impair in-vivo studies. We hypothesized that an NY-ESO-1 T cell receptor (TCR) transgenic mouse would provide the unique opportunity to study avidity of TCR response against NY-ESO-1 for tumor vaccine and cellular therapy development against this clinically relevant and physiological human antigen. Methods To study in vitro and in vivo the requirements for shaping an effective T cell response against the clinically relevant NY-ESO-1, we generated a C57BL/6 HLA-A*0201 background TCR transgenic mouse encoding the 1G4 TCR specific for the human HLA-A2 restricted, NY-ESO-1 157-165 SLLMWITQC (9C), initially identified in an NY-ESO-1 positive melanoma patient. Results The HLA-A*0201 restricted TCR was positively selected on both CD4 + and CD8 + cells. Mouse 1G4 T cells were not activated by endogenous autoimmune targets or a large library of non-cognate viral antigens. In contrast, their activation by HLA-A2 NY-ESO-1 157-165 complexes was evident by proliferation, CD69 upregulation, interferon-γ production, and interleukin-2 production, and could be tuned using a twofold higher affinity altered peptide ligand, NY-ESO-1 157-165V . NY-ESO-1 157-165V recombinant vaccination of syngeneic mice adoptively transferred with m1G4 CD8 + T cells controlled tumor growth in vivo. 1G4 transgenic mice suppressed growth of syngeneic methylcholanthrene (MCA) induced HHD tumor cells expressing the full-length human NY-ESO-1 protein but not MCA HHD tumor cells lacking NY-ESO-1. Conclusions The 1G4 TCR mouse model for the physiological human TCR against the clinically relevant antigen, NY-ESO-1, is a valuable tool with the potential to accelerate clinical development of NY-ESO-1-targeted T-cell and vaccine therapies.
POS0467 STUDY OF METHOTREXATE METABOLITES CONCENTRATIONS IN RED BLOOD CELLS AND MONONUCLEAR CELLS IN RHEUMATOID ARTHRITIS
Authors: V. Sygyrta, G. Gridneva, A. Lila, E. Samarkina, N. Baymeeva, Y. Muraviev, E. Aronova, A. Kudryavtseva
Journal: Annals of the Rheumatic Diseases (2021)

Background: Studying the dynamics of the methotrexate metabolites concentration in cells will help to predict the therapeutic effect and assess patient compliance. We suggest that studying the dynamics of changes in the concentration of methotrexate metabolites in mononuclear cells (MO) may be a more accurate method than measuring in red blood cells (RBC). Objectives: To study the dynamics of changes in the concentration of MTX and its metabolites in RBC and MO in methotrexate-naive patients with RA. Methods: 33 patients (26 women, 7 men) aged 53.2 ± 11.7 years with a diagnosis of rheumatoid arthritis, according to the ACR / EULAR 2010 criteria, were included. All patients had GFR &gt;60 ml/min. Patients were monitored after 4, 12, 24 and 36 weeks from the start of МТX. Mean Cell Volume (MCV) of RBC was measured by standard methods. Samples of RBC and MO were collected separately to determine the concentrations of MTX (basic monoglutamate form), total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), 7- hydroxymethotrexate (7-OH-MTX) by tandem mass spectrometry. Results: Table 1. Total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), nmol/l Me [25;75] Min Max Week 4 RBC 42.8 19.0;155.0 3 987.7 MO 6.2 5.3;11.9 1.6 147.2 Week 12 RBC 48.1 17.1;89.0 0.1 519.9 MO 10.9 3.9;31.0 0.9 147.6 Week 24 RBC 39.4 17.2;70.6 2.7 191.8 MO 8.3 2.7;14.0 0.4 72.4 A pairwise comparison of MTX, MTPG2-4 and 7-OH-MTX concentrations, according to the Wilcoxon method did not reveal statistically significant differences at weeks 4, 12 and 24. The concentration of the studied substances did not correlate with the value of the body mass index, taking statins, glucocorticoids, a cumulative dose of MTX, and the frequency of adverse reactions. At the week 4, of therapy, the level of MTPG4 in MO was inversely correlated with the duration of the disease (correlation coefficient - 0.58, p 0.05) The concentration of MTX and its metabolites in MO was lower in smokers (MTX 11.2 [2.6;21.9], 7-OH-MTX 2.1 [0.5; 10.4], MTPG2 0.5 [0.1;1.3]) than in non-smokers (MTX 46.5 [25.3;97.5], 7-OH-MTX 28.2 [7.1; 64.7], MTPG2 8.2 [4.1;32.9]), p = 0.02, 0.01 and 0.003, respectively. At week 24 of therapy, a negative correlation was found between age and MTPG4 level (correlation coefficient 0.51, p &lt;0.05). Conclusion: The inadequate response to MT therapy in smokers, described in many previous studies, may be associated with a low concentration of the MTX metabolites in mononuclear cells. The level of MTPG4 in mononuclear cells increases more slowly in patients with a longer duration of the disease. Disclosure of Interests: None declared
AB0735 POLYMORPHISMS OF GENES CD14, C-REACTIVE PROTEIN, FIBRINOGEN BETA CHAIN, ASSOCIATED WITH THE DEVELOPMENT OF KAWASAKI DISEASE AND CORONARY ARTERY ANEURYSMS IN CHILDREN FROM CENTRAL RUSSIA
Authors: M. Kantemirova, S. Kurbanova, Y. Novikova, A. Glazyrina, M. Azova, E. Zheludova, E. Tarasenko, D. Ovsyannikov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Kawasaki disease (KD) is a multifactorial disease with a genetic predisposition, systemic vasculitis complicated by the formation of coronary artery aneurysms (CAA). Its pathogenesis is based on immune inflammation with an increase in the concentration of pro-inflammatory cytokines, the level of C-reactive protein (CRP), and coagulation disorder. Objectives: to search for polymorphisms of genes cluster of differentiation CD14, CRP, fibrinogen beta chain (FGB), associated with the KD development and a predisposition to the CAA formation among patients with KD living in Moscow and the Moscow region. Methods: genotyping for gene polymorphisms CD14 –159 C&gt;T (rs2569190), CRP 3872 C&gt;T (rs1205), FGB – 455 G&gt;A (rs1800790) by PCR in 31 children 1 month – 10 years old (median age 19 months [9,0; 38,5]) with KD, among them, in 10 patients the disease was complicated by CAA formation according to echocardiography, and 30 children of the control group. Results: Three out of six investigated SNPs showed statistically significant difference in genotype and allele distribution: СRP C3872T, CD14 C159T and FGB G455A. CRP gene polymorphism: in patients with KD significantly less frequent is homozygous type TT (RR 0,22, 95% CI: 0,05–0,91, p=0,0168). CD14 gene polymorphism: in control group heterozygous genotype CT is predominant, (RR 0,58, 95% CI: 0,4–0,83, p=0,0017) among patients with KD homozygous genotypes CC and TT are predominant. (RR 3,61, 95% CI: 1,14–11,49, p=0,0057). FGB gene polymorphism: genotype GA is predominant in control group (RR 0,48, 95% CI: 0,26–0,9, p=0,0149). In patients with KD significantly less frequent is homozygous type GG (RR 1,69, 95% CI: 1,03–2,8, p=0,0297). We didn’t find any significant difference in genotype and allele distribution in KD patients with and without CA lesions. Conclusion: statistically significant differences (p&lt;0,05) were revealed in the distribution of genotypes for polymorphisms of the CD14 –159 C&gt;T, CRP 3872 C&gt;T and FGB –455 G&gt;A genes among patients with KD and children of the control group; when comparing the results of KD patients with CAA and the control group, statistically significant differences (p&lt;0,05) were revealed only in the polymorphism CD14 –159 C&gt;T. It can be assumed that these polymorphisms are associated with the development of KD and CAA in these patients. Disclosure of Interests: None declared