tbuckley/cabot-search huggingface dataset:
Impact of oncological versus nononcological on survival outcomes in African Americans with renal cell carcinoma.
Authors: Margaret Frances Meagher, Aaron Bradshaw, Dattatraya H Patil, Kazutaka Saito, Brittney Cotta, Yosuke Yasuda, Ahmed Eldefrawy, Yasuhisa Fujii, Viraj A. Master, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2020)

749 Background: African-Americans have an increased incidence of renal tumors of lower oncological potential when compared to other ethno-racial groups. Yet, survival outcomes are similar. We investigated the impact of African-American race on overall survival, oncological and functional outcomes, and non-cancer mortality. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients who underwent partial or radical nephrectomy between 1998-2018. Primary outcome was overall survival (OS). Secondary outcomes were non-cancer mortality (NCM), recurrence free survival (RFS), and eGFR decline. Multivariable logistic regression (MVA) was used to analyze OS, NCM, and RFS, and estimated glomerular filtration rate (eGFR)&lt;45 and &lt;30 ml/min/1.73m2. Results: 3632 patients were grouped into African American (AA, n=531) and Non-African American (NAA, n=3101). No difference was noted between groups with respect to mean tumor size (p=0.31). NAA had a higher proportion of metastases at presentation (9.9% vs. 7.0%, p=0.04). AA race was an independent risk factor for functional decline to de novo eGFR &lt;45 (OR=1.43, p=0.04) and de novo eGFR&lt;30 (OR 2.01, p&lt;0.001). MVA for worsened NCM demonstrated AA race (OR=1.63, p=0.02), increasing age (OR=1.05, p&lt;0.001), male sex (OR=1.56, p=0.01), and hypertension (OR=1.73, p=0.001) to be independent risk factors. Significant factors on MVA for worsened OS included increasing age (OR=1.03, p&lt;0.001), radical nephrectomy (OR=1.47, p=0.01), increasing tumor size (OR=1.11, p&lt;0.001), hypertension (OR=2.63, p&lt;0.001), high tumor grade (OR=1.97, p&lt;0.001), and post-operative eGFR &lt;45 (OR=1.50, p=0.01). MVA for worsening RFS demonstrated high tumor grade (OR=2.04, p&lt;0.001) and increasing clinical tumor size (OR=1.15, p&lt;0.001) to be independent factors. Conclusions: African Americans undergoing surgical management for RCC appear to have similar OS and RFS, but poorer NCM than non-African American patients. The cause of these disparities is multi-faceted but likely is associated with functional decline. Nephron-sparing management when feasible and appropriate should be considered in African-Americans presenting with renal cortical tumors.
Association of Low Baseline Diaphragm Muscle Mass With Prolonged Mechanical Ventilation and Mortality Among Critically Ill Adults
Authors: Michael C. Sklar, Martin Dres, Eddy Fan, Gordon D. Rubenfeld, Damon C. Scales, Margaret S. Herridge, Nuttapol Rittayamai, Michael O. Harhay, W. Darlene Reid, George Tomlinson, Dmitry Rozenberg, William McClelland, Stephen Riegler, Arthur S. Slutsky, Laurent Brochard, Niall D. Ferguson, Ewan C. Goligher
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Low diaphragm muscle mass at the outset of mechanical ventilation may predispose critically ill patients to poor clinical outcomes. <h3>Objective</h3> To determine whether lower baseline diaphragm thickness (Tdi) is associated with delayed liberation from mechanical ventilation and complications of acute respiratory failure (reintubation, tracheostomy, prolonged ventilation &gt;14 days, or death in the hospital). <h3>Design, Setting, and Participants</h3> Secondary analysis (July 2018 to June 2019) of a prospective cohort study (data collected May 2013 to January 2016). Participants were 193 critically ill adult patients receiving invasive mechanical ventilation at 3 intensive care units in Toronto, Ontario, Canada. <h3>Exposures</h3> Diaphragm thickness was measured by ultrasonography within 36 hours of intubation and then daily. Patients were classified as having low or high diaphragm muscle mass according to the median baseline Tdi. <h3>Main Outcomes and Measures</h3> The primary outcome was time to liberation from ventilation accounting for the competing risk of death and adjusting for age, body mass index, severity of illness, sepsis, change in Tdi during ventilation, baseline comorbidity, and study center. Secondary outcomes included in-hospital death and complications of acute respiratory failure. <h3>Results</h3> A total of 193 patients were available for analysis; the mean (SD) age was 60 (15) years, 73 (38%) were female, and the median (interquartile range) Sequential Organ Failure Assessment score was 10 (8-13). Median (interquartile range) baseline Tdi was 2.3 (2.0-2.7) mm. In the primary prespecified analysis, baseline Tdi of 2.3 mm or less was associated with delayed liberation from mechanical ventilation (adjusted hazard ratio for liberation, 0.51; 95% CI, 0.36-0.74). Lower baseline Tdi was associated a higher risk of complications of acute respiratory failure (adjusted odds ratio, 1.77; 95% CI, 1.20-2.61 per 0.5-mm decrement) and prolonged weaning (adjusted odds ratio, 2.30; 95% CI, 1.42-3.74). Lower baseline Tdi was also associated with a higher risk of in-hospital death (adjusted odds ratio, 1.47; 95% CI, 1.00-2.16 per 0.5-mm decrement), particularly after discharge from the intensive care unit (adjusted odds ratio, 2.68; 95% CI, 1.35-5.32 per 0.5-mm decrement). <h3>Conclusions and Relevance</h3> In this study, low baseline diaphragm muscle mass in critically ill patients was associated with prolonged mechanical ventilation, complications of acute respiratory failure, and an increased risk of death in the hospital.
MRC COIN試験において進行大腸癌の初回治療におけるオキザリプラチン‐フルオロピリミジン化学療法へのセツキシマブの追加:反応性のありうる患者のサブセットの同定
Authors: Maughan T, Adams R, Smith C, Seymour M, Wilson R, Meade A, Fisher D, Madi A, Cheadle J, Kaplan R
Journal: Annals of Oncology (2010)
Hancock vows to stamp out “absurd” rationing of some NHS services
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The health secretary Matt Hancock has vowed to stamp out what he described as the “absurd” and “unwarranted” postcode variations in access to certain clinical services on the NHS.

In a keynote speech at the Nuffield Summit 2020 setting out his future priorities for the system, Hancock said that one of two key goals for the NHS—alongside increasing healthy life expectancy—was …
Activation of angiogenic pathway in the prediction of pathologic response to bevacizumab-based neoadjuvant therapy in breast cancer.
Authors: Jose Manuel Lopez-Vega, Elena Galve Calvo, Arrate Plazaola, Serafin Morales, Blanca Hernando, Rosa Maria Sanchez Gomez, Isabel Alvarez, Antonio Anton, Jose J. Illarramendi, Ana De Juan, Purificación Martinez, Ainhara Lahuerta, Antonio Llombart Cussac, Maria Garcia Gonzalez, Juan Lao, Valentina Boni, Teresa Puertolas, Stefan Sherer, Luis Sabariz, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

10595 Background: To evaluate potential biomarkers of pathological response to bevacizumab-based neoadjuvant therapy in untreated breast cancers (BC) patients recruited in a phase II, multicenter clinical trial. Methods: Patients received a single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting in 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5) following by surgery. Biomarker expression was assessed by immunohistochemistry (Ki67, CD31, CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab infusion (C1). Gene expression was analyzed using Affimetrix Human Gene ST 1.0. Results: This analysis was performed on 73 patients (49 yr, range 29-70). Twenty (27%) patients obtained best response (G4-G5) whether 50 (68%) were considered as no responder (G1-G2-G3). Response was associated with negative estrogen receptors expression (p=0.02) and high Ki67 basal and after C1 expression (p=0.009 and p=0.01). Six (54%) of the triple negative tumors were responders (p=0.05). Interestingly, change in pVEGFR2 [Y951] staining induced by bevacizumab administration was found significantly associated with response (p=0.0). Decrease in the phosphorilation status of VEGFR2 (Y951) &gt;70% yielded a receiver operating characteristic (ROC) curve area of 0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The positive and negative predictive values for this marker were 60% and 64%, respectively. The change in phosphorilation status of VEGFR2p remains a significant predictor biomarker of response in multivariate analysis (OR=0.9, IC%95 0.96-0.99, p=0.04) after adjusting for clinical-pathological characteristics. Conclusions: These findings suggest the role of the phosphorilation status of VEGFR2 as predictive biomarkers of pathological response to bevacizumab in neoadjuvant setting in breast cancer.
Long-term treatment with ligelizumab achieves prolonged symptom control during the post-treatment follow-up
Authors: Weily Soong, Jonathan Bernstein, Gordon Sussman, Bobby Lanier, Karl Sitz, Marcus Maurer, Ana Giménez-Arnau, Eva Hua, Avantika Barve, Thomas Severin, Reinhold Janocha
Journal: Journal of Allergy and Clinical Immunology (2020)
In vitro and in vivo degradation behavior of Mg–2Sr–Ca and Mg–2Sr–Zn alloys
Authors: Kai Chen, Xinhui Xie, Hongyan Tang, Hui Sun, Ling Qin, Yufeng Zheng, Xuenan Gu, Yubo Fan
Journal: Bioactive Materials (2020)

Magnesium alloys with integration of degradability and good mechanical performance are desired for orthopedic implants. In this paper, Mg-2Sr-Ca and Mg-2Sr-Zn alloys were prepared and the degradation as well as the bone response were investigated. Compared with the binary Mg-2Sr alloys, the addition of Ca and Zn improved the in vitro and in vivo corrosion resistance. Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited more uniform corrosion and maintained the configuration of the implants 4 weeks post-implantation. The in vivo corrosion rates were 0.85 mm/yr for Mg-2Sr-Zn and 1.10 mm/yr for Mg-2Sr-Ca in comparison with 1.37 mm/yr for Mg-2Sr. The in vitro cell tests indicated that Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited higher MG63 cell viability than Mg-2Sr alloy. Furthermore, these two alloys can promote the mineralization and new bone formation without inducing any significant adverse effects and this sound osteogenic properties suggest its attractive clinical potential.
Dupilumab in Adolescents With Moderate-to-Severe Atopic Dermatitis and a History of Allergic Rhinitis: Subgroup Analysis From a Phase 3 Trial
Authors: Lawrence Sher, Weily Soong, Paola Mina-Osorio, Randy Prescilla, Zhen Chen, Ashish Bansal
Journal: Journal of Allergy and Clinical Immunology (2020)
Characteristics of COVID-19 infection in Beijing
Authors: Sijia Tian, Nan Hu, Jing Lou, Kun Chen, Xuqin Kang, Zhenjun Xiang, Hui Chen, Dali Wang, Ning Liu, Dong Liu, Gang Chen, Yongliang Zhang, Dou Li, Jianren Li, Huixin Lian, Shengmei Niu, Luxi Zhang, Jinjun Zhang
Journal: Journal of Infection (2020)
The road ahead for health and lifespan interventions
Authors: Marta Gonzalez-Freire, Alberto Diaz-Ruiz, David Hauser, Jorge Martinez-Romero, Luigi Ferrucci, Michel Bernier, Rafael de Cabo
Journal: Ageing Research Reviews (2020)

Aging is a modifiable risk factor for most chronic diseases and an inevitable process in humans. The development of pharmacological interventions aimed at delaying or preventing the onset of chronic conditions and other age-related diseases has been at the forefront of the aging field. Preclinical findings have demonstrated that species, sex and strain confer significant heterogeneity on reaching the desired health- and lifespan-promoting pharmacological responses in model organisms. Translating the safety and efficacy of these interventions to humans and the lack of reliable biomarkers that serve as predictors of health outcomes remain a challenge. Here, we will survey current pharmacological interventions that promote lifespan extension and/or increased healthspan in animals and humans, and review the various anti-aging interventions selected for inclusion in the NIA's Interventions Testing Program as well as the ClinicalTrials.gov database that target aging or age-related diseases in humans.
A rational approach to e-cigarettes: challenging ERS policy on tobacco harm reduction
Authors: John Britton, Jacob George, Linda Bauld, Sanjay Agrawal, John Moxham, Deborah Arnott, Ann McNeill, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2020)

<b>The current ERS Tobacco Control Committee statement rejecting harm reduction does not reflect the state of evidence around the effectiveness and safety of e-cigarettes and may be harmful if implemented</b>http://bit.ly/39ix5iO
Superiority of temozolomide over radiotherapy for elderly patients with RTK II methylation class, MGMT promoter methylated malignant astrocytoma
Authors: Antje Wick, Tobias Kessler, Michael Platten, Christoph Meisner, Michael Bamberg, Ulrich Herrlinger, Jörg Felsberg, Astrid Weyerbrock, Kirsten Papsdorf, Joachim P Steinbach, Michael Sabel, Jan Vesper, Jürgen Debus, Jürgen Meixensberger, Ralf Ketter, Caroline Hertler, Regine Mayer-Steinacker, Sarah Weisang, Hanna Bölting, David Reuss, Guido Reifenberger, Felix Sahm, Andreas von Deimling, Michael Weller, Wolfgang Wick
Journal: Neuro-Oncology (2020)

Abstract Background O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation status is predictive for alkylating chemotherapy, but there are non-benefiting subgroups. Methods This is the long-term update of NOA-08 (NCT01502241), which compared efficacy and safety of radiotherapy (RT, n = 176) and temozolomide (TMZ, n = 193) at 7/14 days in patients &amp;gt;65 years old with anaplastic astrocytoma or glioblastoma. DNA methylation patterns and copy number variations were assessed in the biomarker cohort of 104 patients and in an independent cohort of 188 patients treated with RT+TMZ-containing regimens in Heidelberg. Results In the full NOA-08 cohort, median overall survival (OS) was 8.2 [7.0–10.0] months for TMZ treatment versus 9.4 [8.1–10.4] months for RT; hazard ratio (HR) = 0.93 (95% CI: 0.76–1.15) of TMZ versus RT. Median event-free survival (EFS) [3.4 (3.2–4.1) months vs 4.6 (4.2–5.0) months] did not differ, with HR = 1.02 (0.83–1.25). Patients with MGMT methylated tumors had markedly longer OS and EFS when treated with TMZ (18.4 [13.9–24.4] mo and 8.5 [6.9–13.3] mo) versus RT (9.6 [6.4–13.7] mo and 4.8 [4.3–6.2] mo, HR 0.44 [0.27–0.70], P &amp;lt; 0.001 for OS and 0.46 [0.29–0.73], P = 0.001 for EFS). Patients with glioblastomas of the methylation classes receptor tyrosine kinase I (RTK I) and mesenchymal subgroups lacked a prognostic impact of MGMT in both cohorts. Conclusion MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ. It indicates favorable long-term outcome with initial TMZ monotherapy in patients with MGMT promoter-methylated tumors primarily in the RTK II subgroup.
Discordance of HER2 expression in distant metastatic tumors (MTs) versus primary tumors (PTs) in urothelial carcinoma (UC).
Authors: Claud Grigg, Chad Livasy, Jiaxian He, Aaron Hartman, Peter E. Clark, Derek Raghavan, Earle Frederick Burgess
Journal: Journal of Clinical Oncology (2020)

550 Background: Available HER2 targeted agents have limited benefit for UC, but exceptional tumor responses are occasionally seen. HER2 expression has been tested as a biomarker of response to these drugs. Trial eligibility is often based on HER2 expression in PTs. Previous studies found moderate to high concordance of HER2 expression in PTs and synchronous regional nodes at cystectomy, but the concordance rate with distant MTs is poorly defined and further complicated by shifting definitions of HER2 positivity. Methods: Immunohistochemical (IHC) staining for HER2 (Ventana Pathway clone 4B5) was performed on PTs and matched MTs in 79 patients with UC. IHC staining was scored (0-3+) using intensity and % positive tumor cells using 2018 ASCO/CAP guidelines for breast cancer. Fisher’s Exact Test assessed association of PT and MT HER2 scores, and Cohen’s kappa statistic (κ) assessed agreement in HER2 3+ between groups. MTs were defined as synchronous if biopsied &lt;60 days after the PT biopsy. Results: There were 67 metachronous and 12 synchronous paired biopsies; median time between metachronous biopsies was 418 days. MT biopsy sites included lymph node (30%), bone (22%), lung (18%), pelvic/peritoneal soft tissue (11%), liver (8%), brain (4%), other (6%). HER2 2+ and 3+ expression was seen in 30.4% and 12.7% of PTs and 12.7% and 7.6% of MTs, respectively. Of HER2 3+ PTs (n=10), HER2 expression in paired MTs was 0 (n=3), 1+ (n = 3), 2+ (n = 2), and 3+ (n = 2). Of HER2 3+ MTs (n=6), HER2 expression in paired PTs was 0 (n=1), 2+ (n=3), and 3+ (n=2). An association was observed between PT and MT HER2 scores (p=0.004), however there was low agreement of HER2 3+ rates between PT and MT lesions (κ = 0.17, p=0.113). Discordance was noted in both synchronous and metachronous biopsies. Conclusions: Based on the current HER2 3+ definition, HER2 overexpression is spatially and temporally discordant in UC between PTs and distant MTs. These findings suggest that both PTs and MTs should be tested for HER2 expression in future clinical trials assessing the efficacy of HER2 targeted agents in UC. The high discordance may explain previously negative therapeutic studies.
Assessment of Lesion Detectability in Dynamic Whole-Body PET Imaging Using Compartmental and Patlak Parametric Mapping
Authors: Neda Zaker, Fotis Kotasidis, Valentina Garibotto, Habib Zaidi
Journal: Clinical Nuclear Medicine (2020)

Purpose Hybrid dynamic imaging allows not only the estimation of whole-body (WB) macroparametric maps but also the estimation of microparameters in the initial bed position targeting the blood pool region containing the pathology owing to the limited axial field of view of PET scanners. In this work, we assessed the capability of multipass WB 18 F-FDG PET parametric imaging in terms of lesion detectability through qualitative and quantitative evaluation of simulation and clinical studies. Methods Simulation studies were conducted by generating data incorporating 3 liver and 3 lung lesions produced by 3 noise levels and 20 noise realizations for each noise level to estimate bias and lesion detection features. The total scan time for the clinical studies of 8 patients addressed for lung and liver lesions staging, including dynamic and static WB imaging, lasted 80 minutes. An in-house–developed MATLAB code was utilized to derive the microparametric and macroparametric maps. We compared lesion detectability and different image-derived PET metrics including the SUVs, Patlak-derived influx rate constant ( K i ) and distribution volume ( V ) and K 1 , k 2 , k 3 , blood volume (bv) microparameters, and K i estimated using the generalized linear least square approach. Results In total, 104 lesions were detected, among which 47 were located in the targeted blood pool bed position where all quantitative parameters were calculated, thus enabling comparative analysis across all parameters. The evaluation encompassed visual interpretation performed by an expert nuclear medicine specialist and quantitative analysis. High correlation coefficients were observed between SUV max and K imax derived from the generalized linear least square approach, as well as K i generated by Patlak graphical analysis. Moreover, 3 contrast-enhanced CT-proven malignant lesions located in the liver and a biopsy-proven malignant liver lesion not visible on static SUV images and Patlak maps were clearly pinpointed on K 1 and k 2 maps. Conclusions Our results demonstrate that full compartmental modeling for the region containing the pathology has the potential of providing complementary information and, in some cases, more accurate diagnosis than conventional static SUV imaging, favorably comparing to Patlak graphical analysis.
Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model
Authors: Mathilde Coustets, Caroline Ladurantie, Elisabeth Bellard, Mélissa Prat, Marie-Pierre Rols, Vincent Ecochard, Gwenaël Ferron, Sophie Chabot, Muriel Golzio, Laurent Paquereau
Journal: Biomaterials (2020)
Bacterial Nucleoside Catabolism Controls Quorum Sensing and Commensal-to-Pathogen Transition in the Drosophila Gut
Authors: Eun-Kyoung Kim, Kyung-Ah Lee, Do Young Hyeon, Minsoo Kyung, Kyu-Yeon Jun, Seung Hee Seo, Daehee Hwang, Youngjoo Kwon, Won-Jae Lee
Journal: Cell Host & Microbe (2020)
Effect of High-Dose vs Standard-Dose Vitamin D Supplementation in Pregnancy on Bone Mineralization in Offspring Until Age 6 Years
Authors: Nicklas Brustad, Juri Garland, Jonathan Thorsen, Astrid Sevelsted, Martin Krakauer, Rebecca K. Vinding, Jakob Stokholm, Klaus Bønnelykke, Hans Bisgaard, Bo L. Chawes
Journal: JAMA Pediatrics (2020)

Studies suggest an association between maternal vitamin D status during pregnancy and offspring anthropometry and bone mineralization, but investigations are few and with mixed results.To investigate the effect of a high dose vs standard dose of vitamin D supplementation in pregnancy on anthropometric and bone outcomes until age 6 years in the offspring.A prespecified analysis of a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort that included 623 pregnant mothers and their 584 children. Data were analyzed between January 2019 and September 2019.Vitamin D supplementation of 2800 IU/d (high-dose) vs 400 IU/d (standard-dose) from pregnancy week 24 until 1 week after birth.Longitudinal anthropometry assessments including length/height, weight, and body mass index until age 6 years and bone mineral content (BMC) and bone mineral density (BMD) at age 3 years and 6 years from dual-energy radiography absorptiometry scans.At age 6 years, 517 children (89%) completed the clinical follow-up. All participants were Danish and white; 261 were boys and 256 were girls. A mixed-effects model analysis of dual-energy radiography absorptiometry scan outcomes from ages 3 years and 6 years showed that children in the vitamin D vs placebo group had higher whole-body BMC: mean difference adjusted (aMD) for age, sex, height, and weight was 11.5 g (95% CI, 2.3-20.7; P = .01); higher whole-body-less-head BMC aMD was 7.5 g (95% CI, 1.5-13.5; P = .01); and higher head BMD aMD was 0.023 g/cm2 (95% CI, 0.003-0.004; P = .03). The largest effect was in children from vitamin D-insufficient mothers (<30 ng/mL; to convert to nanomoles per liter, multiply by 2.496) and among winter births. In a post hoc analysis, we found borderline lower incidence of fractures in the vitamin D group (n = 23 vs n = 36; incidence rate ratio, 0.62 [95% CI, 0.37-1.05]; P = .08), but no differences in any anthropometric outcomes. Adjustment for a concomitant ω-3 polyunsaturated fatty acids intervention did not change the results.High-dose vitamin D supplementation in pregnancy improved offspring bone mineralization through age 6 years compared with the standard dose, suggesting an increased recommended gestational intake, which may influence peak bone mass, fracture risk, and risk of osteoporosis later in life. We found no supplementation effect on anthropometric outcomes.ClinicalTrials.gov Identifier: NCT00856947.