tbuckley/cabot-search huggingface dataset:
The effect of gender on outcomes in esophageal cancer.
Authors: Jordan McDonald, Sabrina Saeed, Sarah E. Hoffe, Rutika Mehta, Jessica M. Frakes, Jacques-Pierre Fontaine, Sean P. Dineen, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2021)

170 Background: Few epidemiological studies address differences in outcomes by gender in locoregional esophageal cancer (LEC) for which the current standard of care is chemoradiation followed by surgical resection. Although male gender is associated with the majority of LEC cases, we sought to determine if gender could impact clinical presentation as well as surgical and oncologic outcomes in our single institution 20 year experience. Methods: A retrospective query of our institution’s IRB-approved database of patients that had surgical therapy between 2008 and 2019 for esophageal cancer (EC) was performed. Patients were stratified by gender and analyzed based on characteristics such as tumor histology, tumor location, clinical stage at presentation, age at diagnosis, receipt of neoadjuvant therapy, surgical intent, surgical complications, length of post-operative hospital stay, response to neoadjuvant therapy, final pathology, and recurrence. Chi-square, ANOVA and Kaplan Meier survival analysis were performed on the previously defined groups. Results: The cohort studied included 1180 patients with resection for EC. Of those, 1005 (85.2%) had adenocarcinoma, 145 (12.3%) had squamous cell cancer (SCC), 10 (0.8%) had adenosquamous carcinoma, and 20 (1.7%) had other histological variants. There were 985 (83.5%) male patients and 195 (16.5%) female patients. SCC was more common in females (29.2% in females vs. 8.9% in males, p = 0.000) and females tended to have tumor location in the upper thoracic esophagus more often (4.7% in females vs. 0.9% of males, p = 0.000). Additionally, females developed surgical complications more often than males (72.2% vs. 64.7%, p = 0.045). Staging at diagnosis (p = 0.508), receipt of neoadjuvant treatment (p = 0.676), and age at diagnosis (65.3 years in males vs. 66.3 years in females, p = 0.934) had no association with gender. Response to neoadjuvant therapy (p = 0.157) and cancer recurrence (p = 0.434) did not have significant associations with gender. The median overall survival was not statistically significantly different but trended to be longer for females (73.4 months in females [95% CI: 51.5-95.4] vs. 47.0 months in males [95% CI: 39.6-54.5], p = 0.160). Conclusions: Based on our high-volume cancer center study, female patients were more likely to have SCC, upper thoracic esophageal lesions, and surgical complications following resection. While univariate analysis did not demonstrate significant differences in overall survival between genders, there are plans to report additional data after controlling for other variables. Further studies are warranted to validate these findings, given the potential for higher prioritization of an organ preservation approach for this patient population.
THU0005 Increased frequency of hla dr 11 and decreased frequency of hla dr 1 in caucasian europeans with abdominal aortic aneurysms
Authors: A Schmarda, H Schennach, P Klein-Weigel, C Goldberger, D Schönitzer, KP Pfeiffer, G Fraedrich, M Schirmer
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A genetic predisposition has been reported to play a key role in the pathogenesis of abdominal aortic aneurysms (AAA) in Japanese and a subgroup of North American patients with inflammatory AAA. <h3>Objectives</h3> The aim of this study was to evaluate a possible association of HLA DR phenotypes with AAA in a European population sample. <h3>Methods</h3> Consecutive patients with AAA larger than 3 cm presenting at our outpatient clinic were analysed for HLA class II genotypes using the PCR-SSP technique at low resolution level. DR phenotypes were deduced from these results. Patients with any history of an autoimmune disease were excluded from the study. The frequencies of HLA DR phenotypes were compared to those of a cohort of consecutive and ethnically matched organ donors using the appropriate statistical methods. Classification trees have been applied to increase the predictive value and to consider more than one variable. <h3>Results</h3> HLA DR genotyping was performed in 54 European AAA patients (44 males) and 296 controls (203 males). At the HLA DRB1* locus, 19/54 AAA patients (35,2%) and 63/296 controls (21,3%) were found to be 1*11 positive (p = 0,035; OR = 2,01, 95% c.i.: 1,08–3,75). Subanalysis of male patients revealed 17/44 (38,6%) AAA patients and 39/203 (19,2%) in controls to be 1*11 positive (p = 0,009; OR = 2,65, 95% c.i.: 1,31–5,33). Regarding HLA DRB1*01, 4/54 AAA patients (7,4%) and 64/296 controls (21,6%) turned out to be 1*01 carrier (p = 0,014; OR = 0,29, 95% c.i.: 0,10–0,83). Subanalysis of male patients revealed 2/44 (4,5%) and 48/203 (23,6%) DRB1*01 carrier in AAA patients and controls, respectively (p = 0,003; OR = 0,15, 95% c.i.: 0,04–0,66). No associations for DRB1*11 and 1*01 were observed in female patients. <h3>Conclusion</h3> These data suggest a positive association between AAA and DR 11 and a possible protective effect of DR 1 in male Caucasian Europeans suffering from AAA. This finding supports the hypothesis that MHC class II genes play a role in the pathogenesis of AAA.
Inability of granule polarization by NK cells defines tumor resistance and can be overcome by CAR or ADCC mediated targeting
Authors: Jiri Eitler, Natalie Wotschel, Nicole Miller, Laurent Boissel, Hans G Klingemann, Winfried Wels, Torsten Tonn
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background On encountering a susceptible target, natural killer (NK) cells mediate cytotoxicity through highly regulated steps of directed degranulation. Cytotoxic granules converge at the microtubule organizing center and are polarized toward the immunological synapse (IS), followed by granule exocytosis. NK cell retargeting by chimeric antigen receptors (CARs) or mAbs represents a promising strategy for overcoming tumor cell resistance. However, little is known about the lytic granule dynamics of such retargeted NK cells toward NK-cell-resistant tumors. Methods Here, we used spinning disk confocal microscopy for live-cell imaging to analyze granule-mediated NK cell cytotoxicity in ErbB2-targeted CAR-expressing NK-92 cells (NK-92/5.28.z) and high-affinity FcR transgenic NK-92 cells plus Herceptin toward ErbB2-positive breast cancer cells (MDA-MB-453), which are resistant to parental NK-92. Results Unmodified NK-92 cells cocultured with resistant cancer cells showed stable conjugate formation and granule clustering, but failed to polarize granules to the IS. In contrast, retargeting by CAR or FcR+Herceptin toward the MDA-MB-453 cells enabled granule polarization to the IS, resulting in highly effective cytotoxicity. We found that in NK-92 the phosphoinositide 3-kinase pathway was activated after contact with resistant MDA-MB-453, while phospholipase C-γ (PLCγ) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) were not activated. In contrast, retargeting by CAR or antibody-dependent cell-mediated cytotoxicity (ADCC) provided the missing PLCγ and MEK/ERK signals. Conclusions These observations suggest that NK cells can create conjugates with resistant cancer cells and respond by granule clustering, but the activation signals are insufficient to induce granule polarization and consequent release of lytic enzymes. Retargeting by CAR and/or the FcR/mAb (ADCC) axis provide the necessary signals, leading to granule polarization and thereby overcoming tumor cell resistance. Keywords: NK cells, NK-92, haNK, ADCC, Chimeric Antigen Receptor (CAR), breast cancer, cancer immunotherapy, live-cell imaging, granule polarization
Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins
Authors: Vahagn Ohanyan, Sean M. Raph, Marc M. Dwenger, Xuemei Hu, Thomas Pucci, Gregory Mack, Joseph B. Moore, William M. Chilian, Aruni Bhatnagar, Matthew A. Nystoriak
Journal: Circulation Research (2021)

[Figure: see text].
A Treatment Protocol with Imatinib and Intensive Chemotherapy for Pediatric Philadelphia Positive Acute Lymphoblastic Leukemia Patients: A Single-Arm, Intergroup Study (EsPhALL 2010-2014)
Authors: Andrea Biondi, Virginie Gandemer, Myriam Campbell, Anders Castor, Rob Pieters, Paola De Lorenzo, Veronica Leoni, Jan Stary, Gabriele Escherich, Chi Kong Li, Giovanni Cazzaniga, Helene Cave, Silja Roettgers, Valentino Conter, Vaskar Saha, Martin Schrappe, Maria Grazia Valsecchi
Journal: Blood (2017)
The importance of being synchronous: on the prognostic value of ventricular conduction delay in heart failure**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of the JACCor the American College of Cardiology.
Authors: Chistoph Stellbrink, Bernd Nowak
Journal: Journal of the American College of Cardiology (2002)
Reference values for EORTC QLQ-C30, for metastatic pancreatic cancer (mPC): Enhancing the interpretation of HRQoL scores in the POLO trial.
Authors: Hedy L. Kindler, Suvina Amin, Seongjung Joo, Nikunj Patel, Hyun Kyoo Yoo, Colin Johnson, Hilary Byrnes, Sara Costa-Cabral, Sandra Nolte
Journal: Journal of Clinical Oncology (2021)

393 Background: Metastatic pancreatic cancer (mPC) and its treatments significantly impact patients’ (pts) health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in mPC pts who had not progressed during ≥16 weeks of first-line platinum-based chemo. HRQoL was assessed in POLO using EORTC QLQ-C30. To enhance the interpretation of HRQoL scores in POLO, we derived EORTC QLQ-C30 reference (ref) values for mPC from the literature, as these had not been previously established. Methods: A systematic literature review was conducted to identify existing baseline values in published data. EORTC QLQ-C30 ref values were calculated by deriving mean scores based on studies meeting all inclusion criteria. EORTC QLQ-C30 mean values were calculated for POLO using pooled baseline data from both study arms (olaparib; placebo). Results: Out of 186 studies identified, 4 met all inclusion criteria. Depending on respective EORTC QLQ-C30 subscale, the final sample sizes ranged from n=466 to n=639. Compared to the newly derived EORTC QLQ-C30 ref values based on the literature, POLO pts reported markedly better HRQoL scores at baseline across most subscales, with eight subscales showing differences of &gt;15 points (table). Conclusions: This is the first study to systematically derive EORTC QLQ-C30 ref values for mPC. We found that mPC pts enrolled in POLO had better HRQoL scores compared with those reported in the literature and often close to or better than general population norm data, possibly due to positive effects of prior platinum-based first-line treatment, resolution of chemotherapy-related symptoms, response shift, or a combination. These newly derived ref values enhance the interpretation of patients’ HRQoL trajectory within a maintenance treatment setting. [Table: see text]
THU0466 EARLY DIAGNOSIS IS ASSOCIATED WITH LESS DISEASE SEVERITY AND BETTER OUTCOME IN FIBROMYALGIA SYNDROME: A TRICENTRIC PROSPECTIVE ANALYSIS OF A COHORT OF 370 PATIENTS
Authors: A. Moshrif, W. Gouda, M. H. Abu-Zaid
Journal: Annals of the Rheumatic Diseases (2020)

Background: Delayed diagnosis of fibromyalgia (FM) has been reported to be associated with more economic burden, healthcare utilization and worse response to treatment 1,2 . However, its impact on the patients’ symptomatology and disease severity is still underestimated. Objectives: to evaluate the effect of diagnostic delay (DD) on FM severity and disease assessment parameters. Methods: in this cross sectional study, 370 FM patients were prospectively interviewed. Information about DD, widespread pain index (WPI), symptom severity scale (SSS), total severity scale (SSS+WPI) and number of tender points were collected. We proposed to classify our patients into 3 categories; early diagnosis (ED ≤ 2 years; 83 patients), late diagnosis (LD: &gt;2-7 years; 198) and very late diagnosis (VLD &gt;7 years; 89 patients). Results: the mean age of patients was 33.9 (±9.8) and 79.4 % were female. The mean for DD was 5.6 (±3.6) while the means for SSS, total scale and tender points were 7.8 (±1.6), 16.46 (±4.1), 14.31 (±2.3) respectively. A significant correlation has been found for DD with SSS (r = 0.14), total scale (r = 0.37) and tender points (r = 0.16) but not with WPI (r = 0.059). Comparing the three categories, the mean for SSS was 7.54 (±1.6), 7.73 (±1.4) and 8.25 (±1.7) in the groups of ED, LD and VLD respectively (P =0.008) while the mean for the total scale was 15 (±3.8), 15.95 (±3.8) and 18.96 (±4.4) respectively (P = 0.000) and the mean for tender points was 13.7 (±2.3), 14.35 (±2.1) and 14.77 (±2.8) respectively (P = 0.011). The mean for WPI did not significantly differ as it was 7.45 (±2.8), 7.8 (±3.6) and 7.18 (±4.8) in the groups of ED, LD and VLD respectively (P = 0.415). Conclusion: early diagnosis of FM is associated with low SSS, total severity scale and tender points reflecting a better outcome and a less disease severity. References: [1]Hughes G, Martinez C, Myon E, Taïeb C, Wessely S: The impact of a diagnosis of fibromyalgia on health care resource use by primary care patients in the UK: an observational study based on clinical practice.Arthritis Rheum 2006, 54(1):177-83. [2]Choy et al., A patient survey of the impact of fibromyalgia and the journey to diagnosis BMC Health Services Research 2010, 10:102. Disclosure of Interests: : None declared
SAT0252 The impact of rheumatoid arthritis on employment status and social network: a cross-sectional study of 146 patients
Authors: LS Ines, P Reis, MJ Santos, M Alexandre, C Silva, A Branha, A Figueiredo, D Nour, JA Da Silva, A Malcata, A Porto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is recognised as one of the most disabling rheumatic diseases. Work disability and social impairment are frequently overlooked consequences of RA. <h3>Objectives</h3> (1) to evaluate the prevalence of work disability; (2) to evaluate the impact of the disease on the social network in patients with rheumatoid arthritis (RA). <h3>Methods</h3> We submitted a self-report questionnaire concerning RA impact on employment status and social support network to a cohort of 229 patients with RA, fulfilling the 1987 ACR criteria, followed in a hospital-based outpatient rheumatology clinic. 146 patients (63.8%) returned the completed questionnaire (female = 88.4%, male = 11.6%; mean age = 56 years; mean disease duration = 13.4 ± 8.1 years; RF positive = 73.8%; mean Larsen score = 50.6; ACR functional class I ? 20.4%, II ? 26.0%, III ? 30.3%, IV ? 12.7%). <h3>Results</h3> 83.9% of the patients had less than 7 years of formal education. 70.2% had a monthly income of less than 500 euros. 58.7% of the patients were retired and 2.9% unemployed. From these patients, 84.5% had stopped working due to RA. From the employed patients, 5.8% were currently on leave. From all patients, 83.1% had to take a leave at least once due to RA. The mean total time on leave was 587 days per patient. 86.3% of the patients reported that RA compromised their capability to earn money. 81.4% of the patients were married, 7.9% single, 2.9% divorced or separated and 7.9% widowed. All the divorced or separated patients related their status to RA. 88.4% of the patients live with spouse or first grade relatives. Only 2.7% reported to live alone. 72.8% of the patients depend on escort for physician visits, in most of the cases (92.4%) by the spouse. A minority of patients may rely on institutional social support: 7.2% live in a old age residence, 11.2% have access to a day-care centre, 13.3% to a social worker, 12.3% to a religious association and 8.2% to voluntary workers. 89.6% of the patients reported that RA jeopardised the ability to engage in their previous leisure activities. <h3>Conclusion</h3> There was a high prevalence of permanent and temporary work disability related to RA in this cohort. This may be related to the high disease duration of this group. Most patients rely on social support from the family. The impact of RA on marital status was limited, but much more extensive on leisure activities.
Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
Authors: Bernard Combe, Alan Kivitz, Yoshiya Tanaka, Désirée van der Heijde, J Abraham Simon, Herbert S B Baraf, Uma Kumar, Franziska Matzkies, Beatrix Bartok, Lei Ye, Ying Guo, Chantal Tasset, John S Sundy, Angelika Jahreis, Mark C Genovese, Neelufar Mozaffarian, Robert B M Landewé, Sang-Cheol Bae, Edward C Keystone, Peter Nash
Journal: Annals of the Rheumatic Diseases (2021)

To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX).This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities.The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms.Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab.NCT02889796.
FRI0077 Durability and rapidity of response for rheumatoid arthritis patients receiving therapy with anakinra (il-1ra)
Authors: DM Miller, E Ng, MH Schiff, SB Cohen, B Bresnihan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Anakinra (r-metHuIL-1ra) has been shown to be an effective therapy for Rheumatoid Arthritis patients since it improves the signs and symptoms of disease, as measured by ACR criteria. To better characterise this response, we have analysed data from two large, placebo controlled studies of anakinra, given as either monotherapy (MONO) or in combination with methotrexate (MTX). <h3>Objectives</h3> <h3>Methods</h3> To assess the ACR20 response over the time course of the studies, we evaluated the proportion of patients who had a sustained ACR20 response (Sus Resp), defined as at least four ACR20 responses by week 24, with at least one of the ACR20 responses occurring at either week 12 or 24. <h3>Results</h3> Patients receiving anakinra doses &gt;1 mg/kg were 2–3 times more likely than placebo patients to achieve a sustained ACR. The sustained response for both studies was statistically significant. We also evaluated the rapidity of response to anakinra at these doses (&gt; 1 mg/kg). At least 50% of the subjects responding to anakinra achieved an ACR20 response on or before week 4 for either study. <h3>Conclusion</h3> In conclusion, treatment of RA patients with anakinra appears to produce a durable response with a quick onset of action. These factors support the use of anakinra as an effective therapy for rheumatoid arthritis.
<i>Bacteroides uniformis</i> combined with fiber amplifies metabolic and immune benefits in obese mice
Authors: Inmaculada López-Almela, Marina Romaní-Pérez, Clara Bullich-Vilarrubias, Alfonso Benítez-Páez, Eva M. Gómez Del Pulgar, Rubén Francés, Gerhard Liebisch, Yolanda Sanz
Journal: Gut Microbes (2021)

Gut microbiota represents a therapeutic target for obesity. We hypothesize that B. uniformis CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior anti-obesity effects. We performed a 17-week intervention in diet-induced obese mice receiving either B. uniformis, WBE, or their combination to identify interactions and independent actions on metabolism and immunity. B. uniformis combined with WBE was the most effective intervention, curbing weight gain and adiposity, while exerting more modest effects separately. The combination restored insulin-dependent metabolic routes in fat and liver, although the bacterium was the primary driver for improving whole-body glucose disposal. Moreover, B. uniformis-combined with WBE caused the highest increases in butyrate and restored the proportion of induced intraepithelial lymphocytes and type-3 innate lymphoid cells in the intestinal epithelium. Thus, strengthening the first line of immune defense against unhealthy diets and associated dysbiosis in the intestine. This intervention also attenuated the altered IL22 signaling and liver inflammation. Our study shows opportunities for employing B. uniformis, combined with WBE, to aid in the treatment of obesity.
Expanded human NK cells from lung cancer patients sensitize patients’ PDL1−negative tumors to PD1-blockade therapy
Authors: Sophie M Poznanski, Tyrah M Ritchie, Isabella Y Fan, Abdullah El-Sayes, Ana L Portillo, Ronny Ben-Avi, Eduardo A Rojas, Marianne V Chew, Yaron Shargall, Ali A Ashkar
Journal: Journal for ImmunoTherapy of Cancer (2021)

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.