tbuckley/cabot-search huggingface dataset:
AB0532 CORRELATION WITH THE FREQUENCY OF DISEASE RELAPSES DURING THE FIRST 3 YEARS FROM THE DIAGNOSIS AND DISEASE OUTCOMES IN BEHCET’S SYNDROME
Authors: R. Talarico, A. Figliomeni, L. Mione, A. Parma, E. Cioffi, M. Mosca
Journal: Annals of the Rheumatic Diseases (2020)

Background: Beside the organ involvement, a number of demographic factors could considerably influence the long-term and short-term outcomes of Behçet’s syndrome (BS): age at disease onset, duration of disease, gender and sex. Younger men patients are more suitable to have a more severe disease, due to an increased frequency both of morbidity and mortality, related to ocular,vascular and neurological involvement Objectives: The primary aims of the study were to evaluate disease activity in a cohort of BS patients consecutively followed in a BS clinic of a tertiary centre and to explore whether there is a correlation between frequency of relapses in the first 3 years of diseases and disease outcomes. Methods: One-hundred and sixty-five patients (91 males and 74 females; mean age 39±9 years, mean disease duration 9±5) with a diagnosis of BS according to the ISG criteria were studied. Disease activity has been evaluated by BDCAF and patients were also categorized in major or minor involvement of BS according or not to the presence of ocular, neurological and vascular involvement in the course of disease The numbers of relapses in the first 3 years from diagnosis were correlated with disease outcome and damage. Results: At time of the evaluation, 47% of BS patients presented an active disease; 69 patients presented muco-cutaneous involvement, 39 ocular disease, 21 joint involvement, 12 neurological impairment and 9 gastro-enteric involvement. Seventy-nine percent of patients presented in the course of the disease a severe BS involvement and the majority was represented by patients characterised by a more frequent relapse in the first 3 years of disease (M/F: 65/48, mean age 43±3 years). Those patients who experienced a more higher number of relapse in the first 3 years compared to the others were also characterised by poor disease outcomes and worse prognosis over time and this correlation was independent by the therapies taken. Conclusion: The high frequency of relapses during the first three years from diagnosis may be considered an important prognostic factor for disease outcome in BS patients, therefore could be taken into account as a useful element to tailor the management, not only according to the type and severity of symptoms and epidemiological factors. Acknowledgments: none Disclosure of Interests: None declared
Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies
Authors: Paola Rogliani, Beatrice Ludovica Ritondo, Luigino Calzetta
Journal: European Respiratory Journal (2021)

Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS)/long-acting β 2 -adrenoceptor agonist (LABA)/long-acting muscarinic receptor antagonist (LAMA) fixed-dose combination (FDC). Since meta-analyses allow settling controversies of apparently inconsistent results, we performed a network meta-analysis of phase III randomised controlled trials including 9535 patients to assess the effect of ICS/LABA/LAMA combinations in uncontrolled asthma. Triple combination therapies with an ICS administered at high dose (HD) were more effective (p&lt;0.05) than medium-dose (MD) ICS/LABA/LAMA FDC and both MD and HD ICS/LABA FDCs against moderate to severe exacerbation (relative risk 0.61–0.80) and increasing trough forced expiratory volume in 1 s (from +33 to +114 mL). Triple combination therapies including HD ICS were superior (p&lt;0.05) to MD ICS/LABA/LAMA FDC in preventing severe exacerbation (relative risk 0.46–0.65), but not with respect to moderate exacerbation (p&gt;0.05). Triple combination therapies were equally effective on asthma control, with no safety concerns. This quantitative synthesis suggests that ICS/LABA/LAMA FDCs are effective and safe in uncontrolled asthma, and that the dose of ICS in the combination represents the discriminating factor to treat patients with a history of moderate or severe exacerbation.
Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19): an investigator-initiated, randomised, open-label, phase 2 trial
Authors: Cornedine J de Gooijer, Vincent van der Noort, Jos A Stigt, Paul Baas, Bonne Biesma, Robin Cornelissen, Nico van Walree, Robbert C van Heemst, Magdolen Youssef-El Soud, Harry J M Groen, Agnes J Staal-van den Brekel, Wieneke A Buikhuisen, Gerben P Bootsma, Floris Dammeijer, Harm van Tinteren, Ferry Lalezari, Joachim G Aerts, Jacobus A Burgers
Journal: The Lancet Respiratory Medicine (2021)
Are hcv antibodies positive cirrhotic patients at lower risk of death as compared to cirrhotic of different etiologies when infected by COVID-19?
Authors: A. Mangia, G. Verucchi, A. Ciancio, V. Piazzolla, R. Losappio, N. Napoli, G. Lauletta, I. Carraturo, E. Visaggi, G. Mennea, N. Minerva, D. Potenza, M. Mazzola, A. Giannelli, D. Marra, M. Copetti
Journal: Hepatology (2020)

Background: liver injury has been reported at variable rate during COVID-19 outbreak, but the impact of pre-existing liver damage and related etiology has not been detailed so far Methods: we studied the reciprocal impact of COVID-19 and viral or metabolic pre-existing advanced liver diseases in patients consecutively admitted at 3 Italian hospitals during the COVID-19 emergency In this preliminary analysis we analyzed the results of patients enrolled in the observational study from February 28th to April 10th 2020;further analyses will be presented at the meeting Simultaneously, we investigated the prevalence of COVID-19 in patients with all HCV genotypes and any stage of fibrosis or HCV genotype 3 and cirrhosis prospectively enrolled in two real world studies on sofosbuvir/velpatasvir pangenotypic treatment recently published by our collaborative group Results: in the observational study, prevalence of HCVAbs and HBsAg positivity, among 332 COVID-19 infected patients matched recently reported national data Demographic and laboratory results in the table Overall 27 4% and 24 3%, respectively showed increased ALT and AST levels Only 10 patients (3 0%) had HCVAbs, 1 with detectable HCV-RNA, the remaining with spontaneously or treatment-induced HCVRNA clearance The frequency of HCVAbs among subjects with increased ALT at baseline (6 6%) was significantly higher than in patients with normal liver enzymes (1 8%) (p=0 038) Pre-existing cirrhosis was reported in 10, 7 had non viral origin cirrhosis, 70% of non viral origin died Overall mortality was 27 1% Cirrhosis, older age, low white blood cell (WBC) and lymphocyte count were independent predictors of death (OR=6 14, 95%CI 1 11-34 15, p=0 038;OR=1 05, 95%CI 1 03-1 07, p=0 0001, OR=1 10, 95% CI 1 01-1 16;OR=1 06, 95%CI 0 39-0 90, p=0 015) Among HCV patients recently treated with pangenotypic regimen, only 1 (0 07%) with cirrhosis in the pangenotypic study and 2 (1%) in the GT3 cirrhosis study reported COVID-19 ascertained infection, all of them recovered Conclusion: in the observational study, prevalence of HCVAbs is low among patients with COVID-19 Pre-existing cirrhosis is associated with high mortality Whether patients recently cured for HCV infection had a smaller exposure or were less vulnerable to COVID-19 as compared to patients with cirrhosis of metabolic origin deserves further investigation
AB0047 Progression of radiological damage in patients with rheumatoid arthritis in clinical in remission; a prospective two year follow-up study
Authors: ET Molenaar, AE Voskuyl, HJ Dinant, DP Bezemer, BA Dijkmans
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of the present study was to investigate the progression of radiological damage in patients with RA in clinical remission during a follow-up of two years. <h3>Methods</h3> RA patients (n = 187), in remission as defined by the ACR/Pinals Criteria were included. Radiographs of hands and feet were made at baseline, and 2 years. Radiological damage was assessed according to the Sharp-van der Heijde method (score ranging from 0–448; (SHS)). SHS at baseline and after two years were compared in the complete cohort as well as in subgroups of patients with persistent remission and those suffering from excacerbations (Wilcoxon test). The following variables, measured at baseline, were assessed as possible riskfactors for radiological progression: number of tender and swollen joints, Ritchie score, Disease Activity Score (DAS), serum titers of IgM and IgA rheumatoid factors, the visual analogue scale (VAS) for the physicians impression of disease activity and the Health Assessment Questionnaire (HAQ) score. <h3>Results</h3> At baseline and after two years, the mean SHS of the complete group were 49 and 51 (p &lt; 0.001). In the subgroup of persistant remission, the mean SHS were 52 and 53 (p = 0.004). No significant correlations were found between progression of radiographic damage and baseline variables (rho &lt;0.1, p &gt; 0.1). In the subgroup of exacerbation, the mean SHS were 46 and 51 (p &lt; 0.001). Progression of radiographic damage correlated significantly with the following variables at baseline: SHS (rho 0,40), HAQ-score (rho 0.28), serum IgM-RF (rho 0.29), serum IgA-RF (rho 0.25), but not with the VAS and the DAS. <h3>Conclusion</h3> Radiological damage proceeds in RA patients in remission and is not related to disease activity.
SAT0176 Thyroid and bone metabolism
Authors: M Bernardes, A Bernardo, C Vaz, M Ramires, E Mariz, F Brandão, P Valente, A Lopes-Vaz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Hyperthyroidism (HT) is a risk factor for osteoporosis (OP). It is still uncertain if bone mass and bone turnover are completely normalised after treatment of HT. <h3>Objectives</h3> The aim of the present cross-sectional study was to investigate whether former hyperthyroid patients have an increased risk for OP due to reduced bone mass and/or persisting high bone remodelling activity after euthyroidism was restored. <h3>Methods</h3> We studied 53 formerly hyperthyroid females (age39 ± 13 years;20 premenopausal (premw); 33 postmenopausal (posmw), who had been euthyroid for a mean period 129 ± 78 months. They were treated by combined medical therapy.we evaluated bone mineral density (BMD) with Lunar4500 DEXA and calcaneal quantitative ultrasound (QUS) parameters with Osteometer DTUone. Biochemical markers of bone turnover (serum osteocalcin (OC), beta-crosslaps (BCL) and urinary deoxypiridinoline (U-DPR) and cross-linked N-telopeptides of type I collagen (NTX), thyroid hormones and antithyroid antibodies (atb) were measured. <h3>Results</h3> Considering DEXA parameters, in posmw,18% had vertebral OP and 7%had hip OP. A higher prevalence of OP was detected by QUS evaluation:39%BUA tscore«-2,5sd and 42%SOStscore«-2,5sd. There were no cases of OP in premw. Abnormally high levels of U-NTX (35%premw, 61%posmw), U-DPR (26% premw, 15% posmw) and BCL (26% premw, 52% posmw) were found. Significant correlations were detected between U-NTX and TSH (p &lt; 0,05, r = -0,45), U-NTX and free T3 in premw (p &lt; 0,05, r = 0,47), BCL and antithyroidperoxidase atb (p &lt; 0,05, r = 0,56), BCL and antithyroglobulin atb in posmw (p = 0,001, r = 0,59), OC and antithyroglobulin atb in posmw (p = 0,001, r = 0,60) and OC and antithyroidperoxidase atb in posmw (p &lt; 0,001, r = 0,64). There was no correlation between these biomarkers and dose or duration of thyroxin replacement therapy. <h3>Conclusion</h3> The prevalence of OP in former hyperthyroid women wasn`t superior to the general population. There was no significant difference of BMD(Zscores«-2,5 = 0), although these women presented increased bone resorption markers. The discrepancy between DEXA and QUS could reflect differences in “bone quality”. Curiously, dispite being euthyroid, the correlation between U-NTX and TSH could signify that TSH levels close to inferior limit of normality are associated with an increased bone turnover. There is also no explanation to the correlation between biomarkers and antithyroid atbs, but we can`t exclude a possible role of this atbs in the production of BCL or OC. <h3>References</h3> Langdahl, <i>et al</i>. Bone mass, bone turnover, body composition and calcium homeostasis in former hyperthyroid patients treated by combined medical therapy. Thyroid 1996;6(3):161–8 Grant, <i>et al</i>. Is previous hyperthyroidism still a risk factor for osteoporosis in post-menopausal women? Clin Endocrinol. 1995;43:339–45
Comprehensive evaluation of genomic alterations in patients with gastric and gastroesophageal adenocarcinoma stratified according to <i>TP53</i> mutation status.
Authors: Anthony Wood, Yonghong Zhang, Qianxing Mo, Ling Cen, Jacques Fontaine, Sarah E. Hoffe, Jessica M. Frakes, Sean P. Dineen, David T. Pointer, Jose Mario Pimiento, Rutika Mehta
Journal: Journal of Clinical Oncology (2021)

238 Background: Gastric (GC) and gastroesophageal adenocarcinomas (GEA) are molecularly diverse. Molecular biomarkers of clinical significance have been identified that impact treatment decision making. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. However, TP53 mutations have not yet been confirmed as a target of therapeutic benefit. This study aimed to identify distinct genomic alterations that are dominant in TP53 mutated (MUT) versus wild-type (WT) GC and GEA in order to elucidate alternative therapeutic targets within these subsets. Methods: De-identified data for 3741 patients with GC and GEA was obtained from Foundation Medicine. The data obtained were age, gender, tumor mutational burden (TMB), and the distinct genomic alterations noted on DNA sequencing. The dataset was sorted by TP53 mutation status. Differences in mutation frequency were detected using the Fisher’s exact test of independence with a p-value of &lt; 0.01 designated as the cutoff value for statistical significance. Results: The dataset consisted of 2946 GCs and 795 GEAs. TP53 mutations were present in 65.8% of specimens. 61.6% of GCs and 81.4% of GEAs were TP53 MUT positive (p = &lt; .001). Median TMB score and the frequency of tumors with a TMB score &gt; 10 was similar in both TP53 MUT and WT groups. 49 genes had statistically different mutation frequencies in TP53 MUT vs. WT patients. Top co-occurring genetic alterations in TP53 MUT patients included amplification and point mutations in MYC, CCNE1, MET, ERBB2, and EGFR. Amplification and point mutations in MDM2, CDK4, ARID1A, PIK3CA, and ERBB3 were the top co-occurring genetic alterations in TP53 WT patients. Conclusions: There was a high frequency of TP53 mutations in this group of GC and GEA patients, with a higher incidence of TP53 mutations identified in GEA samples. The mutational profiles of these tumors differed according to TP53 mutation status. These differences may be able to serve as the foundation for future clinical investigations.
Identification of transcriptomic determinants to predict the efficacy of anti-EGFR treatment of colorectal cancer patients.
Authors: Saikat Chowdhury, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2021)

130 Background: It is now well known that in colorectal cancer (CRC) activating mutations in KRAS, NRAS, and BRAF confer resistance to anti-EGFR therapy. However, only ~ 40% of patients with RAS WT (KRAS WT /NRAS WT /BRAF WT ) tumors respond to therapy. We have used transcriptomic data in addition to somatic mutations to decipher intrinsic resistance mechanisms and identify novel biomarkers of anti-EGFR response in CRC. Methods: The transcriptomic profiles of metastatic CRC patients treated with the anti-EGFR drug cetuximab plus chemotherapy (n = 193) or as a single agent (n = 80) were retrospectively obtained from two independent clinical cohorts (Okita et al., 2018; &amp; Khambata-Ford et al., 2007). Tumor samples were further divided into RAS WT and RAS Mut groups and subsequently in four consensus molecular subtypes (CMS) based on their transcriptomic profile. The transcriptomic profiles of cetuximab treated CRC cell lines (n = 148, Medico et al., 2015) and PDX models (n = 230, Bertotti et al., 2015) were used for validation. Results: In RAS WT population of cetuximab plus chemotherapy cohort, the disease control rates (DCR) observed for cetuximab in the second line were 92% (33/36) for CMS2 and 83% (15/18) for CMS4 tumors relative to 50% (2/4) and 59% (13/22) for CMS1 and CMS3 respectively (Chi-square test p-value = 0.037). Similarly, in cetuximab single agent cohort, the DCR were 0% (0/4), 68% (15/22), and 29% (5/17) for CMS1, CMS2, and CMS4, respectively (Chi-square test p-value = 0.029). In the preclinical study of 148 CRC cell lines, 60% (12/20) of CMS2 cell lines with RAS WT genes were sensitive to cetuximab, versus no sensitive cell lines from other CMS (CMS1 = 0/4; CMS3 = 0/5; CMS4 = 0/12). In the PDX study, 84% (11/13) of CMS2 tumor showed clinical benefit, followed by CMS4 with 75% (6/8) in RAS WT group (CMS1 = 2/5; CMS3 = 2/4). Gene Set Enrichment Analysis (GSEA) of tumor tissue samples identified that Myc (NES = 1.32, FDR = 0.3), E2F (NES = 2.24, FDR = 0.02), and mTOR (NES = 1.54, FDR = 0.1) pathways were active in the cetuximab refractory RAS WT CMS2 patients relative to cetuximab sensitive tumors. Similarly, these pathways were also activated (FDR ≤ 0.05) in cetuximab resistant RAS WT cell lines and PDX models, suggesting that preclinical models are appropriate for testing of potential therapeutic combinations to overcome resistance to anti-EGFR therapy. Conclusions: Resistance to anti-EGFR therapy in extended RAS WT CRC tumors is mediated in part by transcriptional activation and can be predicted by consensus molecular subtype (CMS) and quantifying transcriptional states of Myc, E2F, and mTOR pathway gene sets.
Retrospective study of nivolumab monotherapy for advanced esophageal squamous cell carcinoma.
Authors: Hayato Mikuni, Shun Yamamoto, Kotoe Oshima, Hidekazu Hirano, Natsuko Okita, Hirokazu Shoji, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Narikazu Boku, Ken Kato
Journal: Journal of Clinical Oncology (2021)

179 Background: Based on the results of the ATTRACTION-1 and ATTRACTION-3 trials, nivolumab monotherapy has used for the treatment of metastatic or recurrence esophageal cancer patients who were refractory or intolerant to fluoropyrimidine and platinum since February 2020 in Japan. However, the ATTRACTION-1 trial mainly included patients who received nivolumab monotherapy as third or later-line treatments, which was different from the ATTRACTION-3 trial which mainly included patients as second-line treatment. Therefore, it is still unclear whether the treatment lines affect the efficacy of nivolumab in clinical practice. Methods: Medical records were retrospectively reviewed for patients diagnosed with metastatic or recurrence esophageal squamous cell carcinoma (ESCC) who received nivolumab monotherapy as second- or third or later-line treatments in our hospital. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) based on the RECIST ver1.1, and the incidences of adverse events (AEs) based on the CTCAE ver5.0. Results: Sixty-two patients were identified as the subject of this study. Thirty patients received nivolumab as second-line treatment (48.4%) and 32 patients as third or later-line treatments (51.6%). The median age (range) were 67 (33-80)/61 (52-84), PS 0 were 40.0/21.9%, prior taxane treatment rate were 6.7/93.8%, respectively. The ORR/DCR were 22.7/45.5% in second-line treatment, and 24.1/44.8% in third or later-line treatments (p=1.00). The median PFS (95% CI) was 2.3 (1.4-6.2)/2.3 (1.2-3.6) months in the second-/third or later-line treatments (HR=0.86, p=0.58). AEs of grade 3 or higher were observed in 6.7/6.3% of the second-/third or later-line treatments. Conclusions: There was no clear difference between second -line and third or later-line treatments in the short-term efficacy of nivolumab monotherapy in advanced ESCC patients.
Concentration of Milataxel (MAC-321, TL-139) and its major metabolite (M-10) in xenograft tumors from mice dosed orally and intravenously
Authors: Hudan Safarpour, Xaio-Jie Tong, Michael Bielawski, Robert Holton, Harley E. Wilcox
Journal: Cancer Research (2006)

512   Milataxel is a novel taxane that has shown substantial anti-tumor activity versus taxane-sensitive and taxane-resistant human tumors in mouse xenograft models. Milataxel has entered phase II clinical studies. Mice implanted with human xenograft tumors (SKMES-lung, HCT-15-colon and A-375 melanoma) were treated with oral and a non-cremophor milataxel IV formulation. Concentrations of milataxel and its major metabolite, M-10, were measured using HPLC-UV-βRAM and LC/MS. Levels for parent and metabolite were found to be different when measuring  14 C labeled species in tumor. M-10 levels were typically 50% higher than parent in tumors from non-Pgp cell lines when milataxel was administered either orally or IV. Measurable levels of parent drug and metabolite persisted for 10 days post dosing. In-vitro IC50 evaluation of Milataxel and M-10 show both to be potent cytotoxics, but M-10 was shown to be a substrate for Pgp. Oral Milataxel has completed a phase I study and plasma levels of M-10 and parent were measured.
Unusual case of a protruding mass in the esophagus successfully treated by endoscopic submucosal dissection
Authors: Bin Ye, Jun Li, Feng Liu
Journal: Endoscopy (2021)

A 65-year-old man presented with a history of progressive dysphagia for 1 month. His physical examination and blood tests showed no abnormalities. He underwent upper gastrointestinal endoscopy three times, which showed a bulky protruding mass in the esophagus at 34 – 39 cm from the incisors ([Fig. 1]). Pathologic findings all revealed inflammatory hyperplasia of epithelial cells and subepithelial granulation tissue. A contrast-enhanced computed tomography (CT) scan showed an intraluminal mass in the lower esophagus ([Fig. 2]), with no evidence of mediastinal lymphadenopathy or any metastases in the chest or abdominal organs. After a multidisciplinary team discussion, we performed endoscopic submucosal dissection (ESD) ([Video 1]), and the lesion was successfully resected en bloc ([Fig. 3]).
Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial
Authors: Raches Ella, Krishna Mohan Vadrevu, Harsh Jogdand, Sai Prasad, Siddharth Reddy, Vamshi Sarangi, Brunda Ganneru, Gajanan Sapkal, Pragya Yadav, Priya Abraham, Samiran Panda, Nivedita Gupta, Prabhakar Reddy, Savita Verma, Sanjay Kumar Rai, Chandramani Singh, Sagar Vivek Redkar, Chandra Sekhar Gillurkar, Jitendra Singh Kushwaha, Satyajit Mohapatra, Venkat Rao, Randeep Guleria, Krishna Ella, Balram Bhargava
Journal: The Lancet Infectious Diseases (2021)