tbuckley/cabot-search huggingface dataset:
Consider active management for premature babies born at 22 weeks, says new guidance
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Doctors working in neonatology should consider stabilisation and resuscitation for all babies born from 22 weeks’ gestation, a week earlier than previously advised, says new guidance from the British Association of Perinatal Medicine (BAPM).1

The change in the Framework for Practice guidance reflects steady improvements made in neonatal and obstetric care over the past decade that have increased survival rates among the most premature babies.

The association said that four in 10 babies born at 23 weeks and receiving treatment in UK neonatal units were now expected to survive, compared with only two in 10 in 2008, when the last guidance was released. However, it warned that, although overall outcomes were improving, some premature infants were still at …
P1.14-33 Canagliflozin Inhibits Lung Cancer Survival and Enhances Its Response to Radiotherapy; Effective Blockade of mTOR Pathway, HIF1a, and Mitosis
Authors: E. Tsakiridis, O. Biziotis, P. Zacharidis, L. Broadfield, B. Mekhaeil, G. Menjolian, T. Farell, B. Abdulkarim, P. Muti, G. Steinberg, T. Tsakiridis
Journal: Journal of Thoracic Oncology (2019)
P2.10-05 Indoor Radon and Lung Cancer Risk. A Pooling Study on the Second Risk Factor for Lung Cancer
Authors: A. Ruano-Ravina, M. Lorenzo-González, M. Provencio, M. Torres-Durán, I. Parente-Lamelas, I. Vidal-García, J. Barros-Dios
Journal: Journal of Thoracic Oncology (2019)
Oxidatively Damaged DNA/RNA and 8-Isoprostane Levels Are Associated With the Development of Type 2 Diabetes at Older Age: Results From a Large Cohort Study
Authors: Ben Schöttker, Yang Xuan, Xīn Gào, Ankita Anusruti, Hermann Brenner
Journal: Diabetes Care (2019)

OBJECTIVE Oxidative stress is believed to play an important role in the pathophysiology of type 2 diabetes, but the few cohort studies that have assessed the association of oxidative stress biomarkers with type 2 diabetes incidence were small and reported inconclusive results. RESEARCH DESIGN AND METHODS We examined the associations of urinary oxidized guanine/guanosine (OxGua) levels (a biomarker of DNA/RNA oxidation) and urinary 8-isoprostane levels (a biomarker of lipid peroxidation) with type 2 diabetes incidence in 7,828 individuals initially without diabetes from a population-based German cohort study with 14 years of follow-up. Hazard ratios (HRs) (95% CIs) per 1 SD were obtained using multivariable-adjusted Cox proportional hazards regression models. RESULTS In the total population, weak but statistically significant associations with type 2 diabetes incidence were observed for OxGua levels (HR [95% CI] per 1 SD 1.05 [1.01; 1.09]) and 8-isoprostane levels (1.04 [1.00; 1.09]). Stratified analyses showed that associations of both biomarkers with type 2 diabetes incidence were absent in the youngest age-group (50–59 years) and strongest in the oldest age-group (65–75 years) of the cohort, with HR of OxGua levels 1.14 (1.05; 1.23) per 1 SD and of 8-isoprostane levels 1.22 (1.02; 1.45) per 1 SD. CONCLUSIONS These results from a large cohort study support suggestions that an imbalanced redox system contributes to the development of type 2 diabetes but suggest that this association becomes clinically apparent at older ages only, possibly as a result of reduced cellular repair capacity.
P2.16-17 Real-World Trends in Systemic Therapy for Nonsquamous EGFR/ALK-Negative Advanced NSCLC (aNSCLC) in the US, 2011–2018
Authors: V. Velcheti, S. Chandwani, X. Chen, B. Piperdi, T. Burke
Journal: Journal of Thoracic Oncology (2019)
P2.01-29 The Correlation Between K-Ras Mutant Subsets with TP53 Mutation and PD-L1 in Non-Small Cell Lung Cancer (NSCLC)
Authors: N. Abdel Karim, C. Onuoha, I. Eldesouki, I. Ahmad, H. Mamdani, A. Spira, A.R. Naqash
Journal: Journal of Thoracic Oncology (2019)
MA07.06 Immunotherapy Re-Challenge After Nivolumab Treatment in Advanced Non-Small Cell Lung Cancer in French Real-World Setting
Authors: M. Giaj Levra, F. Cotté, R. Corre, C. Calvet, B. Jouaneton, R. Jolivel, A. Gaudin, V. Grumberg, J. Assié, C. Chouaid
Journal: Journal of Thoracic Oncology (2019)
A phase I trial of erlotinib (E), cisplatin (C) and radiotherapy (RT) for patients with locally advanced squamous cell cervical cancer
Authors: C. G. Ferreira, M. Salgado, R. Lima, C. Viegas, I. A. Small, K. Fontão, D. Herchenhorn, D. M. Madeira, R. G. Martins, A. N. Rodrigues
Journal: Journal of Clinical Oncology (2006)

13081 Background: Pre-clinical data indicates that inhibition of epidermal growth factor receptor (EGFR) potentiates the effect of RT. This phase I trial aims to determine the maximal tolerated dose (MTD) of erlotinib, an oral EGFR tyrosine kinase inhibitor, when administered concurrently with standard chemoradiation (CRT) for cervical cancer. Methods: In a modified Fibonacci design, two cohorts of three patients received escalating doses of E (50 mg/100 mg) one week before and combined with C (40 mg/m 2 , weekly, 5 cycles) and RT (external beam RT - 5040 cGy in 28 fractions, followed by 4 fractions/700 cGy/weekly of brachytherapy). Eligibility criteria included histologically proven squamous cell cervical carcinoma, stage III; no prior therapy; ECOG PS &lt;3 and adequate end-organ functions. Patients were allowed four additional weeks of toxicity observation after CRT + E before proceeding to the next cohort. Frozen tissue for molecular studies was collected before treatment. Results: Considering the first two cohorts, patients presented median age 48 (36–59), stage IIIB (all patients). Median duration of treatment was 71 (70–104) days. Most common non-hematological toxicity were mild to moderate rash, fatigue, diarrhea (grade 3 in one patient), nausea and dysuria. Grade 3 leukopenia was observed in only one patient. Dose limiting toxicities have not been reported so far. Five patients had complete response and one patient had partial response (MRI). Of note, 5/6 patients reported clinical benefit (bleeding cessation) after one week on E alone. The third study cohort (E = 150 mg) is ongoing. Conclusions: This is the first report of a combination of erlotinib, cisplatin and pelvic RT. The addition of E to standard CRT does not appear to increase in-field or systemic toxicities. MTD has not been defined so far. Final results of the phase I will be presented at the meeting. [Table: see text]
P1.14-57 Post-Ensartinib Outcomes in Refractory Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)
Authors: H. Kim, P. Vu, K. Harrow, C. Liang, G. Selvaggi, E. Weihe, W. Mitchell, L. Bazhenova, S. Patel
Journal: Journal of Thoracic Oncology (2019)
Abstract P185: Racial Disparities in Statin Use Among Persons With HIV: The HIV Electronic Comprehensive Cohort of CVD Complications (HIVE-4CVD)
Authors: Avery Cowen, Anna Pawlowski, Daniel Schneider, Donald M Lloyd-Jones, Matthew J Feinstein
Journal: Circulation (2018)

Background: Few studies have evaluated utilization of ASCVD-preventive therapies, such as statins, among PLWH. Although disparities by race, sex, and insurance status in statin utilization exist in the general population, the extent to which these disparities exist among PLWH - a population with a distinct demographic and risk factor profile - is unknown. Methods: We compared statin utilization rates by race for the 3252 black and white PLWH in HIVE-4CVD who received care at Northwestern Medicine between 1/1/2000 and 5/17/2017. Persons were considered as having an indication for statin therapy if they had one or more of the following: (1) diabetes mellitus; (2) coronary heart disease; (3) a total cholesterol level of ≥240 mg/dL; and/or (4) calculated 10-year ASCVD risk of ≥7.5%. We compared statin utilization between black and white PLWH overall and stratified by insurance status. Multivariable-adjusted logistic regression adjusted for age, sex, and insurance status then was used to compare statin utilization for black vs. white PLWH with statin indications. Results: Of 1680 white PLWH and 1572 black PLWH, 610 whites (36.3%) and 508 blacks (32.3%) had at least one indication for statin therapy. Among PLWH with statin indications, whites were significantly more likely than blacks to be taking statins (60.0% vs. 42.1%, p&lt;0.001; Figure 1). This pattern persisted when analyses were stratified by insurance status. After adjustment for age, sex, and insurance status, black PLWH with statin indications were significantly less likely than their white counterparts to be taking statins (Odds ratio for blacks vs. whites = 0.56 , 95% CI 0.46-0.68, p&lt;0.001). Conclusions: Among PLWH with indications for statin use, blacks were significantly less likely than whites to be taking statins, even after adjustment for age, sex, and insurance status. Further studies of real-world statin use among PLWH are needed to understand reasons for disparities.
Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT
Authors: Jiří Pavlů, Myriam Labopin, Riitta Niittyvuopio, Gerard Socié, Ibrahim Yakoub-Agha, Depei Wu, Peter Remenyi, Jakob Passweg, Dietrich W. Beelen, Mahmoud Aljurf, Nicolaus Kröger, Hélène Labussière-Wallet, Zinaida Perić, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. Methods In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18–72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors. Results In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02–1.39), 1.26 (1.1–1.44), and 1.51 (1.26–1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62–0.90), 0.70 (0.60–0.82), and 0.60 (0.49–0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. Conclusions In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.
EP1.01-31 PET CT Radiogenomic Depiction in PDL1 Expression in Lung Cancer in Indian Population
Authors: R. Tripathi, A. Jajodia, A. Chaturvedi, V.P.B. Koyyala, S. Pasricha, S. Goyal, U. Batra, A. Mehta, H. Prosch
Journal: Journal of Thoracic Oncology (2019)
Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome
Authors: Caitlin J. Bowen, Juan Francisco Calderón Giadrosic, Zachary Burger, Graham Rykiel, Elaine C. Davis, Mark R. Helmers, Kelly Benke, Elena Gallo MacFarlane, Harry C. Dietz
Journal: Journal of Clinical Investigation (2019)

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes the pro-α 1 chain of collagen III. Loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality. We created 2 mouse models of vEDS that carry heterozygous mutations in Col3a1 that encode glycine substitutions analogous to those found in patients, and we showed that signaling abnormalities in the PLC/IP3/PKC/ERK pathway (phospholipase C/inositol 1,4,5-triphosphate/protein kinase C/extracellular signal–regulated kinase) are major mediators of vascular pathology. Treatment with pharmacologic inhibitors of ERK1/2 or PKCβ prevented death due to spontaneous aortic rupture. Additionally, we found that pregnancy- and puberty-associated accentuation of vascular risk, also seen in vEDS patients, was rescued by attenuation of oxytocin and androgen signaling, respectively. Taken together, our results provide evidence that targetable signaling abnormalities contribute to the pathogenesis of vEDS, highlighting unanticipated therapeutic opportunities.
MA02.05 Patient Selection and Early Clinical Outcomes of MR-Guided SABR in 54 Lung Tumors
Authors: T. Finazzi, C. Haasbeek, F. Spoelstra, M. Palacios, M. Admiraal, A. Bruynzeel, B. Slotman, F. Lagerwaard, S. Senan
Journal: Journal of Thoracic Oncology (2019)
P1.04-31 Immunosenescence Correlates with Poor Outcome from PD-(L)1 Blockade but Not Chemotherapy in Non-Small Cell Lung Cancer (NSCLC)
Authors: R. Ferrara, M. Naigeon, E. Auclin, B. Duchemann, L. Cassard, J.J. Medhi, L. Boselli, J. Grivel, A. Desnoyer, M. Texier, L. Mezquita, F. Aboubakar, L. Hendriks, D. Planchard, C. Caramella, J. Remon, M. Ngocamus, C. Nicotra, C. Proto, S. Sangaletti, N. Chaput, B. Besse
Journal: Journal of Thoracic Oncology (2019)
OA02.01 Alectinib in Previously Treated RET-Rearranged Advanced Non-Small-Cell Lung Cancer: A Phase 1/2 Trial (ALL-RET)
Authors: N. Yanagitani, S. Takeuchi, T. Murayama, K. Yoshimura, Y. Imai, S. Takahara, T. Kawakami, T. Seto, Y. Hattori, K. Ohashi, M. Morise, S. Matsumoto, K. Yoh, K. Goto, M. Nishio, S. Yano
Journal: Journal of Thoracic Oncology (2019)

RET rearrangements occur in 1–2% of non-small cell lung cancers (NSCLCs). Alectinib (300 mg twice daily) has been approved for the treatment of ALK-rearranged NSCLC in Japan; it also has a high activity against RET in vitro. A global trial (ALEX study) showed the efficacy and safety of alectinib (600 mg twice daily) in ALK-rearranged NSCLC patients. We conducted a phase 1/2 study of alectinib to establish the recommended dose (RD) and examined its activity in RET-rearranged Japanese NSCLC patients. This study was a single-arm, open-label, multi-institutional phase 1/2 trial. RET-rearranged NSCLC patients treated with at least one regimen of chemotherapy were recruited. RET rearrangements were screened using LC-SCRUM-Japan, a nationwide genomic screening network. In phase 1, alectinib (600 or 450 mg twice daily) was administered, following a 3 + 3 design. The primary endpoint was safety. During phase 2, alectinib at the RD defined in phase 1 was administered. The primary endpoint was the objective response rate in RET inhibitor-naïve patients. Between March 8, 2016 and January 29, 2018, 35 patients were enrolled, and 34 patients were administered alectinib. KIF5B-RET was the most common fusion gene (22 cases [63%]), and the CCDC6-RET fusion was identified in 8 cases. The remaining 5 cases were not distinguishable. In cohort 1 (600 mg twice daily), we observed 5 DLTs (grade 3 rash, increased aspartate aminotransferase, erythema multiforme, thromboembolic event, and increased CPK) in 3 of 6 patients. In accordance with the protocol, we moved to cohort 2 (450 mg twice daily) and observed no DLTs in 3 patients. Additionally, pharmacokinetic analysis indicated that the mean exposure (AUC0–10) of 600 mg twice daily was higher than that previously reported in AF-002JG trial (global phase 1 study). Therefore, we determined 450 mg twice daily as the RD for phase 2. Twenty-five RET inhibitor-naïve patients were treated with the RD, of whom 1 achieved an objective response (4%) and 13 achieved disease control at 8 weeks (52%) as determined by central review. The median progression-free survival was 3.4 months (95% CI 2.0-5.4), and the median overall survival was 19.0 months (5.4-NE). We observed grade 3 neutropenia, pneumonitis, diarrhea, hyponatremia, increased CPK and blood bilirubin (4%) in patients treated with 450 mg alectinib twice daily; no grade 4 adverse events were observed. Alectinib had limited activity in patients with RET-rearranged NSCLC. Further investigation of new targeted therapeutics is required to improve outcomes for these patients.
P1.04-12 Tumor Uptake and Biodistribution of 89Zr-Labeled Pembrolizumab in Patients with Metastatic Non-Small-Cell Lung Cancer
Authors: A. Niemeijer, D. Oprea-Lager, M. Huisman, R. Boellaard, O. Hoekstra, L. De Wit - Van Der Veen, I. Bahce, D. Vugts, G. Van Dongen, E. Thunnissen, E. Smit, J. De Langen
Journal: Journal of Thoracic Oncology (2019)
EP1.17-11 Non-Small Cell Lung Cancer Survival: Gender Inequality After Lung Resection?
Authors: M.T. Tsukazan, A. Vigo, J. Rios, A. Schneider, J.R. Schmitt, T. Lima, R. Ruszkowski, P.A. Schulze, J. Figueiredo Pinto
Journal: Journal of Thoracic Oncology (2019)
EP1.17-04 Pneumonectomy Should Be Avoided in Patients Who Do Not Reach the Distance of 500 Meters in 6-Minute Walking Test Due to High Early Mortality
Authors: T. Marjanski, D. Wnuk, R. Dziedzic, M. Ostrowski, W. Sawicka, W. Rzyman
Journal: Journal of Thoracic Oncology (2019)
Is<i>Mycobacterium tuberculosis</i>infection life long?
Authors: Marcel A Behr, Paul H Edelstein, Lalita Ramakrishnan
Journal: BMJ (2019)

People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. <b>Marcel A Behr and colleagues</b> argue that most of these people are no longer infected
OA08.05 Notch Inhibition Overcomes Resistance to Tyrosine Kinase Inhibitors Promoted by Gate-Keeper Mutations in EGFR-Driven Lung Adenocarcinoma
Authors: E. Bousquet, X. Quantin, J.L. Pujol, K. Wong, J. Soria, J. Mazieres, L. Paz-Ares, A. Maraver
Journal: Journal of Thoracic Oncology (2019)
EP1.06-02 Association of Inflammatory Biomarkers with Overall Survival in Patients with Advanced Malignant Pleural Mesothelioma
Authors: L. Gutiérrez Sainz, P. Cruz, S. Martínez Recio, I. Esteban, F. Arias Lotto, D. Viñal, J. Villamayor, D. Sanchez Cabrero, O. Higuera, J. De Castro Carpeno
Journal: Journal of Thoracic Oncology (2019)
Train emergency medical staff on referring homeless patients for housing, say UK medical colleges
Authors: Susan Mayor
Journal: BMJ (2019)

Healthcare professionals need training on how to refer homeless patients treated in emergency departments to organisations that can provide them with housing, UK medical colleges and homeless charities have advised.1

The organisations were responding to the government’s call for views on implementing the Homelessness Reduction Act 2017.2 The act aimed to provide earlier support to prevent or relieve homelessness. It introduced a new duty on certain public authorities, including NHS emergency departments, to refer homeless people who use their services to a local housing authority.

Andrew Goddard, president of the …
Multifunctional zinc ion doped sol – gel derived mesoporous bioactive glass nanoparticles for biomedical applications
Authors: Zuzana Neščáková, Kai Zheng, Liliana Liverani, Qaisar Nawaz, Dagmar Galusková, Hana Kaňková, Martin Michálek, Dušan Galusek, Aldo R. Boccaccini
Journal: Bioactive Materials (2019)

Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and, more recently, in soft tissue repair and wound healing. In this study we produced mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2-CaO system. With the intention of adding subsidiary biological function, MBGNs were doped with Zn2+ ions. Zn-MBGNs with 8 mol% ZnO content were synthesized via microemulsion assisted sol-gel method. The synthesized particles were homogeneous in shape and size. They exhibited spherical shape, good dispersity, and a size of 130 ± 10 nm. The addition of zinc precursors did not affect the morphology of particles, while their specific surface area increased in comparison to MBGNs. The presence of Zn2+ ions inhibited the formation of hydroxycarbonate apatite (HCAp) on the particles after immersion in simulated body fluid (SBF). No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion. Interestingly, powders containing relatively high amount of zinc released Zn2+ ions in low concentration (0.6-1.2 mg L-1) but in a sustained manner. This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn2+ ions, indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells (MG-63). Additionally, Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs, which could indicate a favourable later attachment of cells. Due to their advantageous morphological and physiochemical properties, Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.
EP1.18-28 Neoadjuvant Therapy Among Patients Undergoing Resection for Non-Small-Cell Lung Cancer: A Single Institution Experience
Authors: L. Gutiérrez Sainz, P. Cruz, J. Villamayor, S. Martínez Recio, I. Esteban, F. Arias Lotto, D. Viñal, D. Sanchez Cabrero, O. Higuera, J. De Castro Carpeno
Journal: Journal of Thoracic Oncology (2019)