tbuckley/cabot-search huggingface dataset:
Phase II trial of nivolumab and metformin in patients with treatment refractory microsatellite stable metastatic colorectal cancer.
Authors: Mehmet Akce, Manali Rupji, Jeffrey M. Switchenko, Walid Labib Shaib, Christina Wu, Olatunji B. Alese, Maria Diab, Gregory B. Lesinski, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2021)

95 Background: Preclinical data suggests metformin can improve immune exhaustion of tumor infiltrating lymphocytes and potentiate the effects of PD-1 blockade. By normalizing the hypoxic TME, metformin was shown to improve cytotoxic T cell function and efficacy of anti-PD-1 antibody in highly aggressive B16 melanoma and MC38 colon adenocarcinoma tumor models. Based on this preclinical rationale we conducted a phase II study with nivolumab and metformin combination in treatment refractory MSS metastatic colorectal cancer (mCRC). Methods: Nivolumab 480 mg IV every 4 weeks and Metformin 1000 mg po twice daily was administered in 28-day cycles following a 14-day metformin only lead-in phase.Eligible patients included stage IV metastatic treatment refractory MSS mCRC (patients must have received oxaliplatin, irinotecan, and fluoropyrimidine), age ≥18 years, ECOG PS 0-1, adequate organ function, no prior anti PD-1 agent. The primary endpoint was overall response rate (ORR). Secondary endpoints included overall survival (OS) and progression free survival (PFS). Simon’s two-stage Minimax design was employed (H 0 : ORR =4%; H 1 : ORR=15%; alpha = 0.1; power =80%). If ≥1 objective response was observed in the first evaluable 18 patients, 10 additional patients would be included in the cohort. ≥3 objective responders in 28 patients would be required to be considered positive study. Pre-treatment and on-treatment research biopsies and correlative peripheral blood specimens were collected. Results: A total of 24 patients were enrolled, 6 patients were replaced per protocol, and 18 patients had evaluable disease. Of the 18 evaluable patients 11/18 (61%) were female, median age 58 [IQR 50-67]. 2 patients had prolonged stable disease (4 and 10 cycles). No patients had objective response based on RECIST 1.1. Median OS and PFS was 5.1 months [95% CI (2-11.7)] and 2.3 months [95% CI (1.7-2.4)], respectively. Most common grade 3 and 4 toxicities were anemia (n=2) and diarrhea (n=2). Conclusions: In treatment refractory MSS mCRCnivolumab and metformin combination was well tolerated. Two patients achieved stable disease, but no objective response was seen; therefore, the study did not proceed with the second stage of enrollment. Immunologic correlative analysis of this study is ongoing. Clinical trial information: NCT03800602.
Sensitive detection of total anti-Spike antibodies and isotype switching in asymptomatic and symptomatic individuals with COVID-19
Authors: Yun Shan Goh, Jean-Marc Chavatte, Alicia Lim Jieling, Bernett Lee, Pei Xiang Hor, Siti Naqiah Amrun, Cheryl Yi-Pin Lee, Rhonda Sin-Ling Chee, Bei Wang, Chia Yin Lee, Eve Zhi Xian Ngoh, Cheng-I Wang, Barnaby Edward Young, Paul A. Tambyah, Shirin Kalimuddin, Surinder Pada, Seow-Yen Tan, Louisa Jin Sun, Mark I-Cheng Chen, Yee-Sin Leo, David C. Lye, Lisa F.P. Ng, Raymond Tzer Pin Lin, Laurent Renia
Journal: Cell Reports Medicine (2021)

Early detection of infection is crucial to limit the spread of coronavirus disease 2019 (COVID-19). Here we develop a flow cytometry-based assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein antibodies in individuals with COVID-19. The assay detects specific immunoglobulin M (IgM), IgA, and IgG in individuals with COVID-19 and also acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of infection. Furthermore, asymptomatic individuals with COVID-19 also develop specific IgM, IgA, and IgG, with IgG1 being the most dominant subclass. Although the antibody levels are lower in asymptomatic infection, the assay is highly sensitive and detects 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic and asymptomatic infections, which may otherwise remain undetected.
Oral ivermectin for a scabies outbreak in a long‐term care facility: potential value in preventing COVID‐19 and associated mortality
Authors: C. Bernigaud, D. Guillemot, A. Ahmed‐Belkacem, L. Grimaldi‐Bensouda, A. Lespine, F. Berry, L. Softic, C. Chenost, G. Do‐Pham, B. Giraudeau, S. Fourati, O. Chosidow
Journal: British Journal of Dermatology (2021)

To-date, COVID-19 pandemic affected >85 million persons worldwide with 14% severe and 5% critical, and a general population case-fatality rate of 1%. Age is the main risk factor for severe disease and death1 making the long-term-care facilities (LTCFs) residents particularly vulnerable.2 COVID-19 therapeutic agents remain sparce and ivermectin, an antiparasitic showed anti-SARS-CoV-2 activity in vitro.3 Moxidectin, another macrocyclic lactone, with a longer plasma half-life, could be considered too.
Investigate the efficacy of immunotherapy for treatment of pancreatic adenocarcinoma (PDAC) with mismatch repair deficiency (dMMR).
Authors: Arish Noor, Luis E. Aguirre, Kirsten Blue, Trenton Avriett, Estrella M. Carballido, Richard D. Kim, Dae Won Kim
Journal: Journal of Clinical Oncology (2021)

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD &gt; 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.
Abstract 13711: Systemic Inflammatory Burden Correlates With Severity and Predicts Outcomes in Patients With Cardiogenic Shock Supported by a Percutaneous Mechanical Support Device
Authors: Nikolaos Diakos, Katherine Thayer, Sarah Newman, Lija Swain, Mohyee Ayouty, Navin K Kapur
Journal: Circulation (2019)

Introduction: In-hospital mortality associated with cardiogenic shock (CS) remains as high as 50%. Inflammation plays a central role in the pathogenesis of heart failure; however, little is known a...
The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer
Authors: Theresa E. Hickey, Luke A. Selth, Kee Ming Chia, Geraldine Laven-Law, Heloisa H. Milioli, Daniel Roden, Shalini Jindal, Mun Hui, Jessica Finlay-Schultz, Esmaeil Ebrahimie, Stephen N. Birrell, Suzan Stelloo, Richard Iggo, Sarah Alexandrou, C. Elizabeth Caldon, Tarek M. Abdel-Fatah, Ian O. Ellis, Wilbert Zwart, Carlo Palmieri, Carol A. Sartorius, Alex Swarbrick, Elgene Lim, Jason S. Carroll, Wayne D. Tilley
Journal: Nature Medicine (2021)
Low gestational vitamin D level and childhood asthma are related to impaired lung function in high-risk children
Authors: Hanna M. Knihtilä, Benjamin J. Stubbs, Vincent J. Carey, Nancy Laranjo, Su H. Chu, Rachel S. Kelly, Robert S. Zeiger, Leonard B. Bacharier, George T. O’Connor, Jessica Lasky-Su, Scott T. Weiss, Augusto A. Litonjua
Journal: Journal of Allergy and Clinical Immunology (2021)
Efficacy of ipilimumab and nivolumab in patients with high-grade neuroendocrine neoplasms.
Authors: Taymeyah E. Al-Toubah, Jennifer Gile, Jonathan R. Strosberg, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2021)

370 Background: Dual checkpoint inhibitor therapy with anti-PD-1 and ant-CTLA-4 therapy has shown promising results in patients with high-grade NENs, demonstrating varying response rates of 9 – 44%. More data are needed to evaluate the true response in a real-world cohort of patients. Methods: Retrospective study of all patients with high-grade neuroendocrine neoplasms treated at the Moffitt Cancer Center and Mayo Clinic between 9/2017 and 7/2020 who received combination therapy with ipilimumab and nivolumab. Primary endpoint was objective response rate. Results: 34 patients met eligibility criteria for evaluation. Patients had received an average of 2 lines of therapy prior to treatment with ipilimumab/nivolumab, including at least one cytotoxic chemotherapy regimen. 27 (79.4%) of patients had poorly differentiated NECs and 7 (20.6%) had well-differentiated high grade NETs. The most common primary site (10, 29.4%) was pancreas; other primary sites of disease included unknown primary (n = 9), colon (n = 5), uterus (n = 3), anorectum (n = 2), esophagus (n = 2), cervix (n = 1), stomach (n = 1), and small intestine (n = 1). 5 patients (14.7%) exhibited a best response of PR per RECIST 1.1 criteria, 9 (26.5%) SD, and 17 (50%) PD: 3 patients did not have a follow-up scan and discontinued treatment shortly after initiation due to clinical progression. ORR was 14.7% and DCR was 41.2%. Median PFS was 1 month (95% CI, 0.45 – 1.55); median OS from time of treatment initiation was 5.0 months (95% CI, 3.42 – 6.59) and median OS from diagnosis was 14.0 months (95% CI, 1.49 – 26.51). Median duration on treatment was 1 month (range 0 – 10 months). 26 patients discontinued treatment for progression, 4 patients for toxicity, and 4 remain on treatment at the time of data cut off. 12 patients (35%) experienced grade 3 and 4 treatment-emergent toxicities: liver transaminitis, elevated blood bilirubin, arthralgia, myalgia, peripheral sensory neuropathy, lower extremity edema, confusion, diarrhea, encephalopathy, acute kidney injury, rhabdomyolysis, myocarditis, and colitis. Conclusions: The ipilimumab and nivolumab regimen has modest activity in aggressive and heavily pretreated high-grade NENs who have progressed on prior cytotoxic chemotherapy. Use of this regimen may be considered in patients with particularly aggressive, refractory high-grade NENs.
Serum pepsinogen as a biomarker for gastric cancer: A nested case-control study using the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial data.
Authors: Haejin In, Patricia Friedmann, Michael Parides, Srawani Sarkar, Philip E. Castle, Meira Epplein
Journal: Journal of Clinical Oncology (2021)

188 Background: Gastric cancer (GC) lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, which is an intermittent phase in the development of GC. A serum based biomarker that indicates increased risk of GC would be useful for targeted prevention strategies. Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large randomized trial conducted over 10 centers in the US between 1993 and 2001. Serum samples were collected at baseline and participants were followed for development of incident GC. ELISA-based pepsinogen tests were conducted on pre-diagnostic serum samples of patients who developed GC and age, sex, and race-matched controls. Pepsinogen negative (PG-) and positive (PG+) status was determined using pepsinogen I (PGI) and pepsinogen I to II ratio (PGR). Those with PGR ≥ 3 and PGI &gt; 70µg/L were considered PG- while those with lower levels on either or both were considered PG+. Cox proportional hazard models were used to determine the hazard ratio (HR) and 95% confidence intervals (95%CI) of PG+ for GC. To examine the association of PG with non-cardia and cardia GC separately, propensity matching was used to create control subsets matched on age, sex, and race. Results: Pepsinogen test results were available on 105 GC cases (70 non-cardia and 35 cardia) and 220 matched controls. Median and range of time from pepsinogen measurement to incident GC diagnosis was 78.6 and 3.0-152.2 months, respectively. GC patients were more likely to be PG+ (31.4% vs 5.5%, p &lt; 0.001) and current smokers (20.0% vs 7.7%, p = 0.004) at baseline than controls. Compared to PG-, PG+ were at an increased risk of any GC (HR = 3.77; 95%CI = 2.50-5.71). After adjusting for family history of GC, smoking, and BMI, PG+ were still at a significantly increased risk of GC compared to PG- (adjusted HR = 4.42; 95%CI = 3.14-6.21). For 138 controls matched to 70 non-cardia cancers, PG+ were at an increased risk of non-cardia GC compared to PG- (HR = 5.65, 95%CI = 3.67-8.70; adjusted HR = 7.26, 95%CI = 4.84-10.90). For 70 controls matched to 35 cardia cancers, PG+ were not at greater risk of cardia GC compared to PG- (HR = 1.79, 95%CI = 0.72-4.44; adjusted HR = 1.95, 95%CI = 0.81-5.37). Conclusions: Pre-diagnostic serum pepsinogen levels from a large prospective cohort study predicted development of non-cardia GC but not cardia GC. PG could be considered as a potential risk biomarker to identify individuals at higher risk of non-cardia GC for targeted screening or interventions.
AB0182 Hip vs calcaneus bone mineral density in postmenopausal women
Authors: JA Román-Ivorra, L Abad, C Fernández-Carballido, JJ Alegre-Sancho
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Assessment of postmenopausal osteoporosis is usually delayed due to central densitometers' lack in some areas. Peripheral densitometers have been proposed for osteoporosis screening. <h3>Objectives</h3> To assess the relationship between bone mineral density (BMD) measurements in post-menopausal women using central (DEXA) and peripheral (PIXI) densitometers. <h3>Methods</h3> 81 women, included in a post-menopausal osteoporosis assessment schedule, were consecutively selected for this study. In all women, we collected: 1) an osteoporosis risk factors' questionnaire; 2) measurement of hip BMD, using a DEXA densitometer (NORLAND); and 3) measurement of calcaneus BMD, using the peripheral densitometer PIXI(LUNAR). <h3>Results</h3> Osteoporosis risk factors collected: mean age (years) = 63(9.6 sd); mean time since menopause (years) = 15.6(9.2 sd); mean body mass index = 28.9(4.5 sd); mother's hip fracture = 6.2%; previous Colles fracture = 8.6%; previous vertebral fracture = 6.2%; previous hip fracture = 1.2%; other non-traumatic fractures = 13.6%; calcium intake &lt; 1 g/d = 88.9%; sedentarism = 45.7%. Statistical significance was found between absolute BMD values (Pearson's correlation coefficient: r = 0.501(p = 0.01)), and t-score values (Pearson's correlation coefficient: r = 0.575 (p = 0.01)) obtained with both densitometers. <h3>Conclusion</h3> Peripheral densitometers can be a reliable and suitable choice for postmenopausal osteoporosis screening in primary health centres.
January blues: Exam season in a pandemic
Authors: Nikki Nabavi
Journal: BMJ (2021)

Although the January blues1 might be familiar, this year’s context has meant that the exam season has been more difficult than ever. If you have taken the stairs at a London tube station, you may be able to draw parallels between this month in our third national lockdown, and the feeling you get as you continue to walk round the curved staircase, thinking “surely I’m nearly there . . .”, without yet being able to see daylight. Yet even as we’re “buffeted by the unwelcome news of a more infective strain of covid, it feels at times as if we’re nearing the end of a long tunnel, with light [vaccines] just around the corner.”2 If you are interested in the new strain, read Sixty seconds on . …
AB0054 The role of the gut in reactive arthritis
Authors: E Rezus, C Chiriac, C Rezus, R Chiriac
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The present study propose to observe the relation between the gut and synovitis in enteretic and urogenic reactive arthritis (ReA). <h3>Methods</h3> Forty patients with ReA were included in the study according to Amor criteria: 25 patients with enteric entrance gate and 15 patients with urogenic entrance gate. We had in view the inflammatory syndrome, immune syndrome, identification of the infectious ?trigger? (serology for Yersinia, Shigella, Salmonella, Chlamydia). Concomitant were effected rectosigmoidoscopy with biopsy and synovial biopsy. <h3>Results</h3> 75% of patients had inflammatory intestinal lesions like active and chronic colitis and proctitis. We found a correlation between persistance of the intestinal inflammation and the evolution of the inflammatory process in the joint. The immunglobulins A were increased at 50% of patients which prove the existence of a persistent antigenic stimulation to the bowel level. At 10 patients with urogenic ReA we observed a remarkable aspect: the presence of subclinical inflammatory lesions to the intestinal mucosa. <h3>Conclusion</h3> The rectosigmoidoscopy with biopsy back the role of the bowel in ReA, even at the patients which have not obvious clinical gastrointestinal manifestations.
Abstract 14698: Correlating Invasive and Noninvasive Evaluation to Determine Volume Status in Patients With Cardiovascular Disease
Authors: Mohammad Rajab, Nayef A Abouzaki, Ryan D Melchior, Parham Parto, Michael C Kontos, Luis A Guzman
Journal: Circulation (2017)

Introduction: Right atrial (RA) pressure is considered the gold standard to assess volume status, with limitations related to its invasive nature. Inferior vena cava (IVC) diameter assessment by ul...
THU0008 Tnf-alpha gene polymorphism in severe and mild rheumatoid arthritis
Authors: M Fabris, L Sinigaglia, S Sacco, E Di Poi, G Favret, GF Ferraccioli
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> TNF-α is thought to be the key driving cytokine in Rheumatoid Arthritis (RA) and recently became a therapeutic target for treatment of patients particularly resistant to conventional therapy. In our study we looked for a genetic background that should indicate some criteria to address RA patients towards more aggressive treatments with anti-TNF-α agents. <h3>Objectives</h3> We assessed the role of the -238 and +489 TNF-α gene polymorphisms in a series of patients with severe aggressive disease who were treated with anti-TNF-α therapy because of their poor response to a DMARDs combination strategy. The phenotypes of these patients were compared to those of a cohort of patients who had a good response to Methotrexate (MTX), thus revealing a mild/moderate disease. <h3>Methods</h3> One hundred and thirty-eight (138) RA patients and sixty-four (64) controls (Healthy Blood Donors, HBD) entered the study. RA patients were divided into 2 subgroups. Group A: 72 rheumatoids, called MTX-responders (MTX-R), who were in stable partial remission since at least six months after MTX treatment (15 mg/w weekly, range 10–25 mg/w). Stable partial remission was defined when patients had less than 3 swollen joints and a morning stiffness of less than 20’. Group B: 68 rheumatoids with still active disease (more than 6 swollen joints and a morning stiffness of at least 60’) despite 6 months of combination therapy (MTX + Sulphasalazine + Hydroxychloroquine or MTX + Cyclosporine, including low doses of prednisone, 5 mg/day). This group subsequently received anti-TNF-α therapy and was labelled as anti-TNF-treated, (TNF-T). Genotyping for -238 and +489 TNF-α polymorphisms was made according to Weiss <i>et al</i>.<sup>1</sup> Statistical analyses (Odds Ratio, 95% Confidence Interval) were performed using Prism Software (Graph-Pad, S. Diego, CA 92121-USA). <h3>Results</h3> MTX-R had an overall frequency of GG homozygousity for the -238 polymorphism of 91.6% vs 92.2% in HBD, while in TNF-T subgroup the GG genotype had a frequency of 100% (OR = 13, CI = 0.7–240, p = 0.008 vs MTX-R). The comparison between TNF-T and HBD is similarly striking (POR = 12, CI = 0.7–230, p = 0.01). The major finding concerning the +489 polymorphism is the lower frequency of the AA genotype in RA in general (OR = 4.2, CI = 1–18, p = 0.01) and in TNF-T in particular. <h3>Conclusion</h3> The GG genotype for the -238 TNF-α polymorphism marks all patients who received anti-TNF-α therapy. This group of patients also showed a significant reduction of the AA genotype of the +489 polymorphism. This latter finding supports the hypothesis that the A allele of the +489 TNF-α intronic polymorphism is linked to a genetic setting that offers a less aggressive phenotype in RA. <h3>Reference</h3> Weiss, <i>et al</i>. N Engl J Med. 1996;334:1090–94
THU0172 The correlation analysis of functional disability indexes with disease activity determinants in women with acute rheumatoid arthritis
Authors: M Býrtane, A Hakguder, M Eryavuz, S Kokino
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease causing joint deformities and consequent functional disability. <h3>Objectives</h3> The aim of this cross-sectional study was to assess the possible correlations between some determinants of (CRP disease activity such as Ritchie articular index (RAI), erytrocyte sedimentation rate (ESR), C-reactive protein) and the functional disability questionnaires in women with acute RA, aged between 50 and 65. <h3>Methods</h3> The functional status of 52 women with acute RA, diagnosed according to modified ARA criteria were assessed by Health Assessment Questionnaire (HAQ) and Lee Functional Index (LFI). Ritchie Articular Index values were determined with joint examination, ESR and CRP with laboratory techniques in blood samples. The relations between these disease activity determinants and functional scores were assessed by correlation analysis. <h3>Results</h3> A strong positive correlation was found between two functional indexes (r = 0.87, p &lt; 0.0001). The significant correlations found between ESR, CRP and LFI (r = 0.31, p &lt; 0.01; r = 0.40, p &lt; 0.001, respectively), were stronger than the positive correlations determined between the same variables and HAQ (r = 0.26, p &lt; 0.05; r = 0.29, p &lt; 0.05, respectively). RAI exhibited stronger correlations with HAQ and LFI when compared with those of laboratory variables with HAQ (r = 0.47, p &lt; 0.01; r = 0.56, p &lt; 0.001, respectively). <h3>Conclusion</h3> The most related disease activity determinants with examined functional disability levels in women with acute RA were observed to be RAI, CRP and ESH, consecutively. The prediction values of joint symptoms seemed to be more prominent when compared with laboratory variables. <h3>References</h3> Jansen LM, van Schaardenburg D, van Der Horst-Bruinsma IE, Bezemer PD, <i>et al</i>. Predictors of functional status in patients with early rheumatoid arthritis. Ann Rheum Dis. 2000;59(3):223–6 McFarlane AC, Brooks PM. Determinants of disability in rheumatoid arthritis. J Rheumatol. 1998;27(1):7–14 Smedstad LM, Moum T, Guillemin F, Kvien TK, <i>et al</i>. Correlates of functional disability in early rheumatoid arthritits: a cross-sectional study of 706 patients in four European countries. Br J Rheumatol. 1996;35(8):746–51