tbuckley/cabot-search huggingface dataset:
SAT0151 Diagnostic criteria of osteoporosis in patients with ra
Authors: S Sohen, M Kamiya, M Ueno, H Kikuchi, T Nonaka, T Hamanishi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> We reported that generalised bone loss was observed in rheumatoid arthritis (RA), especially in post menopausal patients and closely correlate with the activity of RA. On the other hand, glucocorticoids are used in the treatment of active patients with RA. Osteoporosis and related fractures are one of the most serious adverse effects of glucocorticoids. <h3>Objectives</h3> Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis were proposed by American College of Rheumatology and UK Consensus Group. On the other hand, the diagnosis of osteoporosis in patients with RA was usually made by the diagnostic criteria of primary osteoporosis. The purpose of the present study was to clarify the validity of using the diagnostic criteria of primary osteoporosis for the diagnosis of osteoporosis in RA. <h3>Methods</h3> The cutoff values were defined as the value by which the subjects with spine fracture were discriminated from those without spine fracture efficiently in terms of sensitivity and specificity. The subjects and measurement of bone mineral density (BMD) were follows: number of subjects; 256 (47 with vertebral fracture, 219 without vertebral fracture), age of subjects (mean ± SD); fracture group 64.2 ± 9.0 years, non fracture group 59.8 ± 10.9 years, measured site (type of machine); lumbar spine (QDR). Patients treated with glucocorticoid were follows: number of subjects; 103(29 with vertebral fracture, 74 without vertebral fracture), Age of subjects (mean ± SD); fracture group 65.1 ± 12.5 years, non fracture group 54.2 ± 13.6 years. <h3>Results</h3> The cutoff value of all patients with RA was 0.711 g/cm<sup>2</sup> (T score: -2.6, % of the young adult mean (%YAM): 70%). This value was almost same as the cutoff value (BMD: 0.708,%YAM:70%) of osteoporosis proposed by the Japanese diagnostic criteria of primary osteoporosis and as the cutoff value (T score below -2.5) of osteoporosis proposed by the WHO diagnostic criteria. On the other hand, the cutoff value in the patients treated with daily doses of 7.5 mg or more prednisolone was 0.812 g/cm<sup>2</sup> (T score: -1.7,%YAM: 80%). This value was almost same as the value of osteopenia by the Japanese diagnostic criteria (%YAM below 80%) and by the WHO diagnostic criteria (T score below -1.0). <h3>Conclusion</h3> These results supported the validity of using the diagnostic criteria of primary osteoporosis for the diagnosis of osteoporosis in patients with RA. But, in patients treated with daily doses of 7.5 mg or more prednisolone, we have to start the treatment for preventing bone loss, if the patients are diagnosed for osteopenia using the diagnostic criteria of primary osteoporosis.
Phase II study of cabozantinib (cabo) combined with pembrolizumab (pembro) in metastatic or recurrent gastric and gastroesophageal adenocarcinoma (GEC) to overcome resistance to checkpoint inhibitors.
Authors: Farshid Dayyani, Chloe Thomas, Gwendolyn Ung, Thomas H Taylor
Journal: Journal of Clinical Oncology (2021)

TPS253 Background: GEC is the third leading cause of cancer mortality and the fifth most common malignancy worldwide. Fluoropyrimidine and platinum-based combinations are the most commonly used 1L treatment regimens. There are few standard treatment options after 1st line regimens. In the 3L+ GEC Keynote-059 trial, objective response rate (ORR) with Pembro was 15.5% in PD-L1(+) vs. 6.4% in PD-L1(-) tumors. While the responses were durable, the 6-months PFS (6-PFS) was only 14.1% and the median PFS was 2.0 mo. This highlights the remaining unmet need for the majority of patients who either are refractory or develop disease progression following treatment with PD-1 inhibitors in GEC. Cabo plus checkpoint inhibitors have shown clinical benefit in various cancers including hepatocellular, renal cell (RCC), urothelial and castration-resistant prostate cancers. In the CheckMate-9ER trial, Cabo+Nivolumab improved both OS and PFS vs sunitinib in 1L RCC. In patients with RCC who had progression on anti-PD1 inhibitor treatment, Cabo showed promising activity with an ORR of 33% and DCR of 79% (ESMO 2018, abstract 3793). Hypothesis: Based on preclinical and clinical observations, Cabo might contribute to overcoming primary or secondary resistance to PD-1 blockade in GEC. Methods: Prospective, open label, non-randomized phase 2 trial. Eligibility: Diagnosis of GEC, 2+ line of treatment including previous fluoropyrimidine/platinum, ECOG 0-2, adequate organ function, prior checkpoint inhibitor if tumor PD-L1 CPS≥10%. Treatment: Cabozantinib 40mg PO daily, Pembrolizumab 200 mg IV on day 1 of 21d cycle. Primary objective: Feasibility of the combination and estimate of efficacy. Primary endpoint:PFS-6. Secondary objectives: OS, ORR, adverse events. Total number of patients to be enrolled N = 27. Current enrollment (Sep 2020) N = 10. Statistics: If the PFS-6 is &gt; 25%, the study would be regarded as positive, in which case it is planned to expand patient enrollment into a larger single arm phase 2 trial with additional sites to establish the efficacy of the regimen. Clinical trial information: NCT04164979.
A chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity
Authors: Huihui Zhang, Fanlin Li, Jiang Cao, Xin Wang, Hai Cheng, Kunming Qi, Gang Wang, Kailin Xu, Junnian Zheng, Yang-Xin Fu, Xuanming Yang
Journal: Science Translational Medicine (2021)

Although chimeric antigen receptor (CAR)-modified T cells have shown great success in the treatment of B cell malignancies, this approach has limited efficacy in patients with solid tumors. Various modifications in CAR structure have been explored to improve this efficacy, including the incorporation of two costimulatory domains. Because costimulatory signals are transduced together with T cell receptor signals during T cell activation, we engineered a type of CAR-T cells with a costimulatory signal that was activated independently from the tumor antigen to recapitulate physiological stimulation. We screened 12 costimulatory receptors to identify OX40 as the most effective CAR-T function enhancer. Our data indicated that these new CAR-T cells showed superior proliferation capability compared to current second-generation CAR-T cells. OX40 signaling reduced CAR-T cell apoptosis through up-regulation of genes encoding Bcl-2 family members and enhanced proliferation through increased activation of the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase), and PI3K-AKT (phosphoinositide 3-kinase to the kinase AKT) pathways. OX40 signaling not only enhanced the cytotoxicity of CAR-T cells but also reduced exhaustion markers, thereby maintaining their function in immunosuppressive tumor microenvironments. In mouse tumor models and in patients with metastatic lymphoma, these CAR-T cells exhibited robust amplification and antitumor activity. Our findings provide an alternative option for CAR-T optimization with the potential to overcome the challenge of treating solid tumors.
FRI0503 VALIDATION OF THE 2019 ACR/EULAR CLASSIFICATION CRITERIA FOR IGG4-RELATED DISEASE IN A JAPANESE KIDNEY DISEASE COHORT: A MULTI-CENTER RETROSPECTIVE STUDY BY THE IGG4-RELATED KIDNEY DISEASE (IGG4-RKD) WORKING GROUP OF THE JAPANESE SOCIETY OF NEPHROLOGY
Authors: T. Saeki, M. Kawano, T. Nagasawa, Y. Ubara, Y. Taniguchi, M. Yanagita, S. Nishi, M. Nagata, Y. Yamaguchi, T. Saito, H. Nakashima
Journal: Annals of the Rheumatic Diseases (2020)

Background: The 2019 ACR/EULAR classification criteria for IgG4-RD have recently been published 1) . In the criteria, patients with an inclusion criteria score of &gt;20 without exclusion criteria are classified as having IgG4-RD. Objectives: To validate the 2019 ACR/EULAR classification criteria for IgG4-RD in a Japanese kidney disease cohort. Methods: The study involved Japanese patients diagnosed as having kidney disease between April 2012 and May 2019, for whom sufficient clinical information and data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were known. These patients were classified as having IgG4-RKD or non-IgG4-RKD (mimickers) based on the 2019 ACR/EULAR classification criteria for IgG4-RD, and the results were evaluated by expert opinion. Results: Among 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The final diagnoses among the mimickers were vasculitis (n=11), idiopathic tubulointerstitial nephritis (TIN) (n=5), drug-induced TIN (n=5), Sjögren’s syndrome (n=4) and others. Among the 55 true IgG4-RKD patients, 4 had exclusion criteria, and 50 of the remaining 51 had an inclusion criteria score of ≥20 points (sensitivity 90.9%). On the other hand, 49 of the 50 mimickers were classified as having non-IgG4-RKD (specificity 98.0%) (Table 1). Table 1. General characteristics and prevalence of individual items of true IgG4-RKD and non-IgG4-RKD (mimicker) IgG4-RKD (true IgG4-RKD) (n=55) Non-IgG4-RKD (mimicker) (n=50) P Age at diagnosis, mean ±SD (years) 69.9 ± 9.4 56.7 ± 17.4 &lt;0.001 Male (%) 76.4 44 0.001 Elevated serum IgG4 54/55 (98.2%) 18/50 (36.0%) &lt;0.001 Serum IgG4 (mg/dl), mean±SD 1028 ± 796 226 ± 261 &lt;0.001 Dense IgG4+Plasma cells (&gt;10/hpf) in the kidney biopsy 48/51 (94.1%) 13/40 (32.5%) &lt;0.001 Storiform fibrosis in the kidney biopsy 28/51 (54.9%) 3/50 (6%) &lt;0.001 Hypocomplementemia 39/55 (70.1%) 7/42 (16.7%) &lt;0.001 Renal pelvis thickening/ soft tissue 5/55 (9%) 1/50 (2%) 0.20 Bilateral renal cortex low-density areas 29/55 (52.7%) 7/50 (14.0%) &lt;0.001 Exclusion criteria present 4/55 (7.3%) 22/50 (44%) &lt;0.001 Total inclusion criteria points &gt;20 without exclusion criteria 50/55 (90.9%) 1/50 (2%) &lt;0.001 Conclusion: The 2019 ACR/EULAR classification criteria for IgG4-RD showed good agreement with expert classification in this Japanese kidney disease cohort. References: [1] Wallace ZS, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 79:77-87, 2020 Disclosure of Interests: None declared
OP0119 Radiological progression in patients with early rheumatoid arthritis is significantly retarded by combination therapy with methotrexate and cyclosporin-a compared to cyclosprin-a alone
Authors: AH Gerards, RB Landewé, AP Prins, GA Bruijn, HS Goei The, BA Dijkmans
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Cyclosporin-A (CsA) added to low dose methotrexate (MTX) in patients with advanced rheumatoid arthritis (RA) is clinically superior to MTX alone.<sup>1</sup> The potential of CsA and MTX to inhibit radiological progression has not been established yet. <h3>Objectives</h3> To assess in patients with early, active and potentially aggressive RA whether the combination of CsA and MTX results in less radiological progression as compared to CsA alone. <h3>Design</h3> A randomised double blind placebo controlled trial of 48 weeks duration. <h3>Methods</h3> 120 patients with active RA: mean age 52 yrs, mean disease duration 3 months, 95% rheumatoid factor positive, 49% erosions and/or joint space narrowing. Patients received CsA and MTX or CsA and placebo. MTX was started at 7.5 mg/week, and was increased to 15 mg/week after 16 weeks. CsA was started at 2.5 mg/kg/day, and was increased to a maximum of 5 mg/kg/day. Plain X-rays of hands and feet were obtained at week 0 and week 48 and were read in chronological order by two independent observers, blind for the study medication, using the Larsen-modified Larsen score.<sup>2</sup> <h3>Results</h3> The Table 1 summarises the Larsen Score of patients in which 2 sets of films were available. <h3>Conclusion</h3> CsA and MTX significantly retards radiological progression in comparison with CsA alone in patients with early, active and potentially aggressive RA. <h3>References</h3> Tugwell. NEJM 1995;333:137–41 Larsen. J Rheum. 1995;22(10):1974–5
tidybulk: an R tidy framework for modular transcriptomic data analysis
Authors: Stefano Mangiola, Ramyar Molania, Ruining Dong, Maria A. Doyle, Anthony T. Papenfuss
Journal: Genome biology (2021)

Abstract Recently, efforts have been made toward the harmonization of transcriptomic data structures and workflows using the concept of data tidiness, to facilitate modularisation. We present tidybulk, a modular framework for bulk transcriptional analyses that introduces a tidy transcriptomic data structure paradigm and analysis grammar. Tidybulk covers a wide variety of analysis procedures and integrates a large ecosystem of publicly available analysis algorithms under a common framework. Tidybulk decreases coding burden, facilitates reproducibility, increases efficiency for expert users, lowers the learning curve for inexperienced users, and bridges transcriptional data analysis with the tidyverse. Tidybulk is available at R/Bioconductor bioconductor.org/packages/tidybulk .
Abstract 14025: Evacetrapib Alone or in Combination With Different Statin Doses Results in Differential Effect on Lipoproteins and MACE Rates: The ACCELERATE Trial
Authors: Jeffrey S Riesmeyer, Giacomo Ruotolo, Govinda Weerakkody, Wolski Kathy, Ellen McErlean, Venu Menon, Michael A Lincoff, Steven E Nissen, Stephen J Nicholls
Journal: Circulation (2018)

Background: Potential benefits of pharmacological CETP inhibition are likely to reflect lowering of apoB-containing lipoproteins as opposed to HDL-C raising. However, genetic studies have shown tha...
Extracorporeal Membrane Oxygenation and Coronavirus Disease 2019
Authors: Chakradhar Venkata, Vinaya Sermadevi, Michael Plisco
Journal: JAMA Surgery (2021)

To the Editor We read with interest the study by Mustafa et al1 describing the experience of venovenous extracorporeal membrane oxygenation (ECMO) for coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome (ARDS), published in JAMA Surgery.
AB0055 Sulphasalazine in the treatment of rheumatoid arthritis: a 2 year prospective study
Authors: J Morovic-Vergles, K Berdnik-Gortan, D Soldo-Juresa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Sulphasalazine has been suggested as a less effective drug than some of the other disease modifying antirheumatic drugs (DMARDs). It is more suitable for use in milder disease. Sulphasalazine is often the most common first-choice DMARDs because of its good tolerability. <h3>Objectives</h3> The aim was to determine the efficacy and tolerability of long-term sulphasalazine treatment of rheumatoid arthritis (RA). <h3>Methods</h3> This study examines the response to sulphasalazine (2,0 – 3,0 g daily) over a 2 year period in 40 consecutive patients with severe, active RA. This was defined as seropositiva, erosive RA and persistent activity. Clinical evaluation were performed by the same physician every 3 months and also blood count, erythrocyte sedimentation rate (ESR), serum creatinine, liver blood test and urine were obtained. <h3>Results</h3> 40 patients were enrolled in the study. Their mean age at entry to trial was 51,2 ± 11,6 years with a mean duration of disease activity of 4 years. After 3 months of the treatment 21 patients showed no significant clinical improvement. A good clinical response was shown by the improvement of the pain, as well as the reduction of the morning stiffness. Reduction in the acute phase response was shown by improvement in the ESR and C-reactive protein (CRP). Of the 40 patients enrolled in the study, 27 showed highest improvement in swollen joints (p &lt; 0,01), in the duration of morning stiffness (p &lt; 0,01), ESR (p &lt; 0,05), CRP (p &lt; 0,05) after 6 months compared to pretreatment valves. 2 patients were excluded from study because of an leukopenia, and gastrointestine disturbances and in 2 the drug was ineffective. <h3>Conclusion</h3> This study confirmed that sulphasalazine is well tolerated and suggests that patients with severe and active RA could achieve good clinical response to sulphasalazine.
Stage IV gastrointestinal stromal tumors: Epidemiology, treatment and outcomes in adult US patients.
Authors: Johannes Uhlig, Stacey Stein, Jill Lacy, Michael Cecchini, Kevin Kim
Journal: Journal of Clinical Oncology (2021)

462 Background: To evaluate epidemiology, treatment and outcomes of stage 4 gastrointestinal stromal tumors (GIST). Methods: The 2010-2016 United States National Cancer Database was queried for adult patients diagnosed with invasive GIST (ICD code 8936) at AJCC stage 4, without prior malignant disease. Overall survival (OS) was evaluated using Cox proportional hazards regression, accounting for potential confounders in multivariable models. Results: A total of 1,578 stage 4 GIST were included (13.3% of all GIST) with a male:female ratio of 1.38:1. The most common cancer site was the stomach (55.4%) and small intestine (40% of stage 4 GIST). At diagnosis, median age was 62 years and median tumor diameter 10 cm. Distant organ metastases were reported in 58.7%, the most frequent being hepatic (n = 801, 50.8% of stage 4 GIST). The majority of stage 4 GIST patients received systemic therapy (78.6%), either alone (35.4%) or combined surgery+systemic therapy (43.3%). Systemic therapy was administered neoadjuvant in 6.9%, adjuvant in 32%, and neoadjuvant+adjuvant in 5.1% of surgically resected patients. Another n = 204 patients (12.9% of all stage 4 GIST) were treated with surgical resection alone. GIST overall survival rates were 88%, 77%, 67% and 51% at 1, 2, 3, and 5 years, respectively. On multivariable Cox proportional hazard models, primary GIST treatment independently affected OS: compared to combined surgery+systemic therapy, OS was shorter for patients receiving systemic therapy alone (HR = 2.77 (95% CI: 2.12-3.61, p &lt; 0.001)) and no treatment (HR = 4.2 (95% CI: 2.75-6.43, p &lt; 0.001)). No significant OS difference was evident comparing surgery+systemic therapy and surgery alone (HR = 1.23 (95% CI: 0.88-1.72, p = 0.227)). In subgroup analyses of patients undergoing surgical resection, no statistically significant OS difference was evident comparing neoadjuvant, adjuvant and combined neoadjuvant+adjuvant systemic therapy on multivariable analyses. Treatment at non-academic vs. academic centers was associated with shorter OS (multivariable HR = 1.36 (95% CI: 1.1-1.69, p = 0.005)). Further independent OS predictors were male sex (vs. female HR = 1.28 (95% CI: 1.03-1.59, p = 0.023)), older age, higher comorbidities, higher cancer grade, and larger cancer diameter. Conclusions: Stage 4 GIST is a rare gastrointestinal malignancy that most commonly manifests in the stomach and small intestine in male patients, with frequent hepatic metastases and excellent 5-year OS rates of up to 51%. Combined surgery+systemic therapy demonstrates best outcomes, although surgical resection alone might yield comparable results in selected patients.
Endoscopic internal drainage and low negative-pressure endoscopic vacuum therapy for anastomotic leaks after oncologic upper gastrointestinal surgery
Authors: Carlo Felix Maria Jung, Rachel Hallit, Annegret Müller-Dornieden, Mélanie Calmels, Diane Goere, Ulriikka Chaput, Marine Camus, Jean Michel Gonzalez, Marc Barthet, Jérémie Jacques, Romain Legros, Thierry Barrioz, Fabian Kück, Ali Seif Amir Hosseini, Michael Ghadimi, Steffen Kunsch, Volker Ellenrieder, Edris Wedi, Maximilien Barret
Journal: Endoscopy (2021)

Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques.Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure.35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively.EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.
FRI0244 Ultrasonographic features of knee soft tissues in patients with benign joint hypermobility syndrome
Authors: AG Belenkiy, MV Severinova, ES Mach
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Pain in the knee joints is a common rheumatologic complaint among patients with benign joint hypermobility syndrome (BJHS). There structural causes of artralgia in BJHS are unclear. Usually any structural abnormalities are not found during physical examinations. We used the ultrasonografó (US) to examine of knee tissues in individuals with BJHS and symptomatic or asymptomatic knee joints. <h3>Objectives</h3> <h3>Methods</h3> 26 women (w), age 16–25, with BJHS were examined. The first group consisted of 13 w with BJHS and the knee pain (Beigthon score &gt; 5; 6 bilateral and 7 unilateral pain, 19 painful joints); the second group consisted of 13 w with BJHS without knee pain at the moment of the US examinations (26 joints). BJHS individuals were then compared with 10 healthy w (third group) of the same age without joint hypermobility and without knee pain (Beigthon score &lt; 4; 20 joints). The US examinations were performed using a 7,5 MHz linear probe. The following knee tissues were examined: synovia, fluid in the joint, cartilage of the femur condyles, collateral ligaments (CL), tendon of the m.semimembranosus. <h3>Results</h3> In the 1st group (BJHS+, pain+) following abnormalities were found: oedema of the CL ? 8, tenosynovitis of the m.semimembranosus (TMS) ? 9, thickness of the synovia &gt; 3 mm ? 1 and small poplyteal cyst ? 1 case per 19 painful joints. In 4 cases there was a combination of the 2 US features. In only 3 out of 19 symptomatic knee joints did the US not find any abnormalities. In the 2nd group (BJHS+, pain-) oedema of the CL was found in 8, TMS in 8 cases. A combination of both was detected in 2 cases. Overall, in 14 out of 26 asymptomatic knee joints, the US found the same morphologic changes as those in the painful joints. The was no difference between 1st and 2nd BJHS groups in prevalence oedema of the CL or TSM (ð &gt;0,05). In only 1 case out of 20 controlled joints (BJHS-, pain-) was the TMS detected. The differences between 1st and 3rd, 2nd and 3rd groups were highly significant (p = 0,000 and p = 0,0005 accordingly). There were no differences between the groups regarding to thickness of the cartilage, fluid in the joint and thickness of the synovia. <h3>Conclusion</h3> The characteristic US morphologic changes of the periarticular tissues are detected in knee joints in patients with BJHS. These abnormalities are typical of BJHS itself but not of painful joints. This fact may reflect the possible presence of subclinical soft tissues injuries in some individuals with BJHS.