tbuckley/cabot-search huggingface dataset:
Multicenter phase II study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PII).
Authors: Masato Kondo, Hironaga Satake, Motoko Mizumoto, Akira Miki, Takanori Watanabe, Norimitsu Tanaka, Kenro Hirata, Hiroaki Tanioka, Yoshihiro Okita, Takahisa Kyogoku, Mitsutoshi Tatsumi, Koreatsu Matoba, Shinichi Adachi, Satoshi Kaihara, Hisateru Yasui, Akihito Tsuji
Journal: Journal of Clinical Oncology (2020)

399 Background: Prognosis for locally advanced gastric cancer (LAGC), such as clinical T4 disease, bulky nodal metastases, type 4 and large type 3 gastric cancer, was not satisfactory even by D2 gastrectomy followed by adjuvant chemotherapy. Neoadjuvant chemotherapy is another promising approach, therefore, we have conducted a phase II study to evaluate the efficacy and safety of the neoadjuvant chemotherapy of S-1 and oxaliplatin (G-SOX) followed by gastrectomy with D2/3 lymph node dissection for LAGC, and the primary endpoint of curative resection rate was met [Miki A, ESMO 2019]. We show longer follow-up data from this study. Methods: Patients with adenocarcinoma of the stomach; clinical T4; clinically resectable gastric cancer of type 4 or large type 3; bulky nodal involvement around major branched arteries to the stomach were enrolled. Patients receive two cycles of neoadjuvant chemotherapy with S-1 (80 mg/m2, p.o., days 1-14 followed by 1 week rest) and oxaliplatin (130 mg/m2 at day 1), followed by D2 or higher surgery with no residual disease. Patients with pathological R0/1 resection received S-1 (80 mg/m2, p.o., days 1-28 followed by 2 week rest) for 1 year as adjuvant chemotherapy. Primary endpoint was curative resection rate. Results: Between August 2015 and March 2017, forty-one patients were in enrolled. Of the patients, 39 patients (95%) completed the two courses of neoadjuvant chemotherapy of G-SOX, 37 (90%) received gastrectomy, and 36 (87.8%) received curative resection (R0/1). Grade 3 or higher toxicities during neoadjuvant chemotherapy of G-SOX were neutropenia (7%), fatigue (7%), diarrhea (5%) and thrombocytopenia (2%). No treatment related deaths were observed. Surgical complications including postoperative complications were observed in 13 patients (35%). Pathological response rate after neoadjuvant G-SOX was 40%. With a median follow-up period of 33.8 months, 3year-relapse free survival and 3year-ovearll survival was 54.3% and 73.1%, respectively. Conclusions: An update analysis confirmed that neoadjuvant chemotherapy of G-SOX is a feasible and might be one of the promising strategies for patients with LAGC. Clinical trial information: UMIN000018661.
Abstract 190: Does Gender Matter? Addressing the Question of Gender Superiority in Resuscitation Leadership
Authors: Elizabeth D Rosenman, Anthony Misisco, Jeffrey Olenick, Anne K Chipman, Marie C Vrablik, Sarah M Brolliar, Colleen Kalynych, James Grand, Georgia T Chao, Steve W Kozlowski, Rosemarie Fernandez
Journal: Circulation (2019)

Introduction: Effective team leadership is linked to better patient care during resuscitations. Several studies suggest a relationship between team leader gender and the quality of resuscitation leadership and clinical care. However, these studies have been either (1) retrospective investigations that do not capture clinical care processes or (2) simulation-based research involving novice medical student subjects. The objective of this study is to compare the quality of team leadership and clinical care between male- and female-led trauma resuscitation teams. Hypothesis: We hypothesize that team leader gender is not associated with differences in trauma team leadership and clinical care Methods: We performed a secondary analysis of prospectively acquired data by analyzing video recordings of trauma resuscitations at a Level 1 trauma center. Subjects (n=60) included 2 nd and 3 rd year emergency medicine and surgery residents functioning in the team leader role. Two video recorded observations for each participant (n=120) were coded for team leadership and clinical care by two sets of raters balanced with regard to gender and blinded to study hypothesis. Duplicate coding was performed on 10% of the observations. We analyzed data using random coefficient modeling (RCM), controlling for patient injury severity score and subject postgraduate training year. Results: We found no significant difference between men and women on team leadership behavior (p=.43; Men: M=7.63, SE = 0.54; Women: M = 8.67, SE = 0.74) nor on clinical care (p=.39; Men: M = 62.32, SE = 1.50; Women: M = 64.87, SE = 2.57). Effect sizes were modest in favor of women and nonsignificant for both team leadership behavior ( d = .26) and clinical care ( d =.21). Conclusion: Our prospective evaluation of team leadership quality and clinical care during trauma resuscitations does not support a male performance advantage, contradicting previous simulation-based work. Focusing on effective team leadership behaviors, not inherent traits and leadership styles, will allow resuscitation leaders to optimize their individual and team performance, irrespective of gender. Further work is needed to develop training and cognitive aids capable of supporting team leadership during complex resuscitative care.
BMA accepts new GP contract deal after requirements for primary care networks are pared back
Authors: Abi Rimmer
Journal: BMJ (2020)

The BMA has accepted a package of changes to the GP contract for 2020-21, which includes scaled back requirements for primary care networks (PCNs) and funding to attract GPs into partnerships.

The announcement comes after the BMA’s General Practitioners Committee (GPC) rejected a proposed updated contract from NHS England in January and condemned the work that primary care networks (PCNs) are expected to deliver over the next four years.1

As part of the newly accepted contract, draft service specifications for PCNs—outlining the responsibilities of these groups of practices and community providers in the coming years —have been significantly pared back.

GPs will no longer be asked to perform fortnightly care home visits as earlier proposed.2 Instead, working with a community multidisciplinary team, it will be for PCNs to decide who delivers a weekly review of those care home residents, based on clinical …
hPG80 (Progastrin), a novel blood-based biomarker for detection of neuroendocrine neoplasms.
Authors: Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne M. Arnold, Léa Payen, Gaelle Lescuyer, Pierre Liaud, Thierry Cousin, Madison Sands, Dana Napier, Mark B Evers, Dominique Joubert, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2020)

e15038 Background: Neuroendocrine neoplasms (NENs) are heterogeneous tumors which originate from various organs and are of variable aggressiveness based on grade and morphology. Current biomarkers for NENs lack sensitivity and specificity, especially for high-grade NENs (small and large cell neuroendocrine carcinomas). hPG80, progastrin, is a novel bio-marker which is easily measured in plasma using an ELISA test. Physiologically, hPG80, an 80 amino acid protein, is the precursor of the gastrointestinal hormone gastrin. It is synthetized by gastric antrum G cells, and then processed into gastrin by multiple enzymatic processes. In pathological conditions, the GAST gene, which encodes hPG80, was shown to be over-expressed in human solid tumors from various primary sites. hPG80 is unprocessed and released from the tumor cells and becomes detectable in the blood. This study is the first to explore hPG80 in NENs. Methods: hPG80 was quantified in the plasma from 31 NEN patients using DxPG80 technology (ECS-Progastrin, Switzerland). Additional 69 samples are currently undergoing analysis. Progastrin concentrations in 18-70 YO (n = 557) and 18-25 YO (n = 137) healthy blood donors were compared to 31 stage IV NENs patients. The study was IRB approved. Results: Current data are for 31 patients. Data on total 100 patients will be presented at ASCO 2020. Mean age of study cohort at the time of blood collection was 60.9 years. 21 patients had grade 1 and 2 well differentiated NET. 10 patients had high grade NEN (Small cell, large cell and poorly differentiated NEC). High grade sub cohort also included two well differentiated grade 3 NET patients. Mean hPG80 in NENs was 14.17 pM as compared to 2.04 pM and 0.99 pM in 18-70 and 18-25 YO control groups (p &lt; 0.0001), respectively. Subgroup analysis of NENs revealed mean hPG80 of 24.61 pM in high-grade NENs (n = 10) vs 10.88 pM in G1/2 NETs (n = 21). Conclusions: This first-ever study of plasma hPG80 in NENs suggests hPG80 may be a diagnostic blood-based biomarker in both low and high-grade NENs and further study is warranted. A prospective trial is ongoing in high-grade NEN to evaluate its role in monitoring of disease (NCT03958045) and further studies in low-grade NETs are underway. This research was supported by Cancer Center Support Grant (CCSG) from the National Cancer Institute (P30 CA177558) and ECS Progastrin.
Oligometastatic colorectal cancer: Prognostic implications of tumor load, role of locoregional treatments, and of first-line therapy intensification—A pooled analysis of TRIBE and TRIBE2 studies by GONO.
Authors: Gemma Zucchelli, Roberto Moretto, Daniele Rossini, Sara Lonardi, Sabina Murgioni, Giuseppe Tonini, Samanta Cupini, Margherita Ratti, Federica Urbano, Michela Libertini, Carlotta Antoniotti, Salvatore Corallo, Angela Buonadonna, Roberto Bordonaro, Vincenzo Ricci, Emiliano Tamburini, Roberta Grande, Giuseppe Aprile, Alfredo Falcone, Chiara Cremolini
Journal: Journal of Clinical Oncology (2020)

12 Background: According to the ESMO guidelines a metastatic spread involving up to 2 or occasionally 3 sites with 5 or sometimes more metastases (mts) is defined as oligometastatic disease (OMD) and the possibility to offer locoregional treatments (LRTs) should be carefully considered. Tumor load and treatment’s objective (cytoreduction vs disease control) are included among factors affecting the choice of the intensity of the upfront chemotherapy (CT). Nevertheless, no data from clinical trials adopting this definition are currently available, so that the prognostic effect of tumor load, the impact of LRTs and the magnitude of benefit from the CT-intensification in OMD remain unclear. Here we assess the effect of FOLFOXIRI/bev compared to doublets (FOLFOX or FOLFIRI)/bev and the impact of LRTs according to tumor load (OMD vs non-OMD) in a pooled analysis of two randomized phase III studies (TRIBE and TRIBE2). Methods: Subgroup analyses for ORR, PFS and OS were performed according to tumor load at baseline. OMD was defined as up to 5 mts, up to 3 mts in one organ, up to 3 affected organs, mts size ≤ 3 cm, absence of ascites and peritoneal, bone and central nervous system mts. Results: Among 1187 patients (pts) enrolled, 1158 were classifiable: 126 as OMD (11%) and 1032 as non-OMD (89%). Pts with OMD had longer PFS (14.3 vs 10.5 months (mos); p &lt; 0.01) and OS (44.3 vs 24.0 mos; p &lt; 0.01) compared with those with non-OMD. These results were confirmed in multivariable models (p &lt; 0.01). Also among pts who underwent LRTs with curative intent during first line (N = 202), those with OMD at baseline (N = 35) reported longer OS than those with non-OMD (59.6 vs 50.6 mos; p = 0.04). The benefit provided by FOLFOXIRI/bev compared to doublets/bev was confirmed in the OMD subgroup with no interaction effect between treatment arm and tumor load in terms of ORR, PFS and OS (p for interaction = 0.10, 0.58 and 0.23, respectively). Conclusions: OMD is confirmed as a positive prognostic factor and is associated with a higher magnitude of long-term benefit from LRTs than non-OMD. The positive impact of the intensification of the upfront CT is independent of tumor load.
Racial and socioeconomic disparities in overall survival in colorectal cancer (CRC) at West Cancer Center (WCC), Memphis, TN.
Authors: Vanessa Wookey, Gabriella Bufalino, Gregory A. Vidal, Bradley G. Somer, Lee S. Schwartzberg, Axel Grothey
Journal: Journal of Clinical Oncology (2020)

80 Background: WCC, a comprehensive regional community oncology center in Memphis, Tennessee and the Mid-South region, serves a racially, geographically and socioeconomically diverse patient cohort. We sought to evaluate disparity of outcomes in survival by race and socioeconomic status, in addition to patient and tumor characteristics. Methods: All consecutive patients referred to and treated at WCC with colorectal adenocarcinoma from 2007-2013 were included. Individual chart review was performed to verify diagnosis, stage, and date and cause of death. Kaplan-Meier Overall Survival curves were generated for the entire cohort and by race, sex, tumor location and income derived from zip code. WCC survival data were compared to SEER data. Results: From 2007-2013, 1,176 patients were included in the analysis: 405 blacks, 757 whites, 14 others. Median age at diagnosis: Blacks 58 yrs, whites 61 yrs. Stage distribution at diagnosis: stage 1: 100, stage 2: 275, stage 3: 425, stage 4: 376. All stages combined, blacks trended towards shorter OS vs whites (5-year OS: 52.8% vs 58.3%; median survival 71.0 mos vs 98.6 mos; p= 0.095). Blacks presented at later stages (71.4% at stage 3 or 4 vs 66.3% for whites) but no statistically significant OS differences were seen when compared by stage. Patients at or below the median income of $39,590 for WCC had worse 5-year OS (51.6% vs. 61.1%; p= 0.006), as did patients without private insurance (5-year OS: uninsured: 48.0%, Medicare/Medicaid: 50.0%, private: 62.0%; p&lt; 0.001). Adjusted for stage, 5-year OS was statistically significant for stage 4 (private: 18.0%, Medicare/Medicaid: 9.4%, uninsured: 8.3%; p= 0.020). A higher proportion of blacks were below the median income (69% vs 39%) but no statistically significant OS differences were seen when adjusted by race. Overall, cancer survival outcomes were similar to SEER results. Conclusions: At WCC, black patients with CRC presented at a later stage than whites, however, adjusted for stage, no significant racial difference in OS was found. Income and insurance status affected survival outcomes. Overall, our results reveal racial and socioeconomic disparities in colorectal cancer in a diverse US population.
Food allergy immunotherapy: Oral immunotherapy and epicutaneous immunotherapy
Authors: Edwin H. Kim, Arvil Wesley Burks
Journal: Allergy (2020)

Abstract IgE‐mediated food allergy remains a significant and growing problem across the globe. Of the various treatment modalities, oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) have been the best studied. Across various studies of OIT for egg, milk, and peanut allergy, strong levels of desensitization have been shown. With egg and peanut OIT, a limited remission, or sustained unresponsiveness (SU), has further been demonstrated. These advances have been further validated by successful phase 2 and phase 3 studies of peanut OIT. EPIT, using daily administrations of a proprietary patch, demonstrated efficacy as well as safety and tolerability in parallel phase 2 studies; however, its phase 3 study did not meet its primary efficacy outcome. Despite its good track record of desensitization, the safety and tolerability of OIT has remained a question. EPIT, on the other hand, has proven safe and tolerable; however, the adequacy of its desensitization has remained to be determined. As OIT and EPIT continue their march toward regulatory review, optimizations for immunotherapy and novel therapies continue to be developed providing hope for food allergy patients everywhere.
E-selectin plays a major role in DMBA cutaneous carcinogenesis
Authors: Nabiha Yusuf, Aneeqa Iqbal, Megan Norstedt, Craig A. Elmets
Journal: Cancer Research (2006)

4771  Selectins are found on endothelial cells,leukocytes and platelets and are involved in trafficking of cells of the immune system,T-lymphocytes and platelets.They are involved in constitutive lymphocyte homing and in chronic and acute inflammation process including skin inflammation.E-selectin is expressed only on endothelial cells following activation by inflammatory cytokines and contributes to tumor growth and metastasis,possibly by increasing tumor angiogenesis and the adhesion of tumor cells to endothelial cells at distant sites. P-selectin is expressed on stimulated endothelial cells and activated platelets and mediates leukocyte rolling on stimulated endothelial cells and heterotypic aggregation of activated platelets onto leukocytes. It also mediates heterotypic aggregation of activated platelets to cancer cells and adhesion of cancer cells to stimulated endothelial cells.However, there is little information on the role of selectins in the pathogenesis of cutaneous carcinogenesis caused by polyaromatic hydrocarbon Dimethylbenz(a)anthracene(DMBA).In the present study, we attempted to elucidate the role of E- and P-selectin in DMBA induced cutaneous carcinogenesis by using E- and P-selectin knockout mice on a Balb/c background. When subjected to a standard two-stage cutaneous carcinogenesis protocol, using DMBA as tumor initiator and TPA as promoting agent epicutaneously, the number of tumors per mouse was much greater (p  P-selectin > WT indicating that the difference lied at the promotion stage of two stage cutaneous carcinogenesis. These results thus indicate that E-selectin has a major role to play in the development of DMBA cutaneous carcinogenesis.
Real-world outcomes in pancreatic adenocarcinoma (PDAC) and persona types with implications for standard of care (SOC) therapy (Tx).
Authors: Emanuel Petricoin, Michael J. Pishvaian, Patricia DeArbeloa, Daniel Barg, Dzung Thach, Jonathan Robert Brody, Lynn McCormick Matrisian, Vincent Chung, Andrew Eugene Hendifar, Sameh Mikhail, Davendra Sohal, Edik Matthew Blais
Journal: Journal of Clinical Oncology (2020)

735 Background: Molecular profiling (MP) for PDAC has gained increased acceptance and we previously demonstrated that targeting actionable mutations can improve patient (pt) outcomes. However, the correlations of diverse patterns of molecular alterations with outcomes following SOC Tx are largely unknown. Methods: We analyzed longitudinal outcomes of 1355 PDAC pts who underwent MP and received SOC Tx. “Persona” types were established based on the molecular characteristics of each pt using unsupervised clustering, as well as a supervised review defined by our molecular tumor board, following classifications reported in previous studies. Progression-free survival (PFS) for each type was assessed based on the choice of first-line Tx (i.e. FOLFIRINOX [FFX] vs. gemcitabine + nab-paclitaxel [GA]). Statistical comparisons were made against all other types within a specific Tx group. Results: The prognostic/predictive value of the persona types for 1 st -line Tx revealed distinct differences in outcomes (Table). As expected, the DDR deficiency type was associated with a significantly improved PFS for pts treated with FFX but not for GA. In addition, pts in the cell cycle type had a worse PFS compared to other persona types for both FFX and GA. Using this platform, we will further subdivide the persona types into molecular subtypes and associate these with pt outcomes. Conclusions: Our analyses demonstrate that specific molecular persona types exist in PDAC pts and can be linked to Tx outcomes. Ultimately, knowing the persona type/subtype early in a pt’s Tx course may help personalize Tx to improve outcomes. [Table: see text]
An assesment of eczema apps
Authors: L.S. Galen, X. Xu, M. Koh, S. Thng, J. Car
Journal: British Journal of Dermatology (2020)

Eczema is the most common skin disease. One in five people are affected during their lifetime and this number is still increasing, especially in low‐income countries. Smartphone apps could help patients and carers to understand their disease and the treatment. Current research has not yet focused on the quality of eczema apps. Given the possible benefits and pitfalls, these apps should be tested to guide clinicians and patients in recommending and using the most appropriate and safe apps. This work was performed by a digital health research team from Singapore. The authors performed a systematic assessment of the quality of all English, Chinese and Spanish self‐management eczema smartphone apps available from June to November 2018. The assessment criteria were based on international eczema guidelines. The results showed that 98 tested apps had diverse functionalities with varying quality. Most apps failed to name their source of information, and even apps with information provided by qualified doctors were not consistent with guidelines. This is concerning, particularly with regards to certain medication (steroids) where information about appropriate use, dosing, and side effects should be clearly explained, as concerns about their side‐effects are a common reason for their underuse and a major barrier to appropriate treatment. The study concluded that eczema apps have not yet reached their full potential. The large variety in quality of eczema apps highlights the need for guidance on how 1) to develop health apps and 2) to help clinicians make personalized recommendations to patients and caregivers. This summary relates to the study: Eczema apps conformance with clinical guidelines: A systematic assessment of functions, tools and content
Abstract 15720: A Telemonitoring Program for Primary and Secondary Prevention of Cardiovascular Disease
Authors: Savina Nodari, Laura Lupi, Fulvio Glisenti, Gianfranco Gensini, Ilaria Papa, Mariangela Piazzani, Davide Fabbricatore, Gianmarco Arabia, Francesco Gabbrielli
Journal: Circulation (2018)

Introduction: Cardiovascular diseases (CV) have a high prevalence and incidence and are associated with a high rate of mortality and hospitalization, resulting in high costs and poor quality of lif...
COPY-NUMBER SIGNATURES AND MUTATIONAL PROCESSES IN HIGH GRADE SEROUS OVARIAN CARCINOMA
Authors: Geoff Macintyre, Teodora E. Goranova, Dilrini De Silva, Darren Ennis, Anna M. Piskorz, Matthew Eldridge, Daoud Sie, Liz-Anne Lewsley, Aishah Hanif, Cheryl Wilson, Suzanne Dowson, Rosalind M. Glasspool, Michelle Lockley, Elly Brockbank, Ana Montes, Axel Walther, Sudha Sundar, Richard Edmondson, Geoff D. Hall, Andrew Clamp, Charlie Gourley, Marcia Hall, Christina Fotopoulou, Hani Gabra, James Paul, Anna Supernat, David Millan, Aoisha Hoyle, Gareth Bryson, Craig Nourse, Laura Mincarelli, Luis Navarro Sanchez, Bauke Ylstra, Mercedes Jimenez-Linan, Luiza Moore, Oliver Hofmann, Florian Markowetz, Iain A. McNeish, James D. Brenton
Journal: Clinical Cancer Research (2019)