tbuckley/cabot-search huggingface dataset:
Outcome analysis for melanoma patients undergoing deep pelvic lymph node dissection
Authors: B. Badgwell, Y. Xing, J. Gershenwald, J. Lee, P. Mansfield, M. Ross, J. Cormier
Journal: Journal of Clinical Oncology (2007)

8514 Background: The benefits of deep pelvic lymph node dissection (DLND) for node-positive melanoma patients continue to be debated. The objective of our analysis was to assess factors associated with metastatic disease to deep pelvic nodes and examine survival outcomes following DLND. Methods: We retrospectively reviewed the records of 804 patients undergoing lymph node dissection (1990-2001). 97 patients underwent a superficial inguinofemoral lymph node dissection along with a DLND for indications which included: suspicious radiologic imaging (n= 31), documented superficial disease and concern for deep involvement (n = 57), and in-transit disease undergoing limb perfusion (n=9). Logistic regression was performed to identify factors associated with the metastatic tumor spread to deep nodes. Associations between clinicopathologic factors and disease-specific survival (DSS) were estimated using the Cox proportional hazards model. Results: Fifty-four patients (56%) had metastatic disease (median 2 positive lymph nodes, range 1–12) within their deep pelvis. With a median follow-up of 7.5 years, the 5-year DSS was 42% for patients with positive deep pelvic nodes and 52% for those with negative deep pelvic nodes (p = 0.07). When the number of metastatic deep nodes was stratified, the 5-year DSS for patients with 1 positive node, 2–3 positive nodes, and &gt;3 positive nodes was 49%, 48%, and 27%, respectively (p = 0.04). Age ≥ 50 years (odds ratio [OR] = 3.5, p = 0.03), increasing number of positive superficial nodes (OR = 2.1, p &lt; 0.001), and suspicious findings on pelvic CT images (OR = 11.9, p &lt; 0.001) were associated with metastatic deep nodes. In the multivariate analysis, the number of positive deep nodes (hazard ratio [HR] = 1.1, p = 0.03), male gender (HR = 1.9, p = 0.03), and extra-capsular nodal extension of tumor (HR = 2.7, p &lt; 0.001) were identified as adverse prognostic factors for DSS. Conclusions: Survival outcomes in patients with melanoma metastatic to ≤ 3 deep pelvic lymph nodes are comparable to those in patients without deep nodal involvement. These favorable outcomes support an aggressive surgical approach (i.e., DLND) in patients ≥ 50 years, with multiple positive superficial nodes, and suspicious CT findings. No significant financial relationships to disclose.
Prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay, England, June to August 2019
Authors: David J Roberts, Grahame S Davis, Michelle J Cole, Dixita Naik, Hitiksha Maru, Neil Woodford, Peter Muir, Paddy Horner, Ian Simms, George Thickett, Paul Crook, Kirsty Foster, Nick Andrews, John Saunders, Helen Fifer, Kate Folkard, O Noel Gill
Journal: Eurosurveillance (2019)

We identified two new Chlamydia trachomatis (CT) variants escaping Aptima Combo 2 (AC2) assay detection, in clinical specimens of two patients. One had a C1514T mutation the other a G1523A mutation, both within the AC2 23S rRNA target region. The prevalence of such variants among persons tested for CT in England was estimated to be fewer than 0.003%.
Evaluation of Continuous Tumor-Size–Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer
Authors: Tomasz Burzykowski, Elisabeth Coart, Everardo D. Saad, Qian Shi, Dirkje W. Sommeijer, Carsten Bokemeyer, Eduardo Díaz-Rubio, Jean-Yves Douillard, Alfredo Falcone, Charles S. Fuchs, Richard M. Goldberg, J. Randolph Hecht, Paulo M. Hoff, Herbert Hurwitz, Fairooz F. Kabbinavar, Miriam Koopman, Timothy S. Maughan, Cornelis J. A. Punt, Leonard Saltz, Hans-Joachim Schmoll, Matthew T. Seymour, Niall C. Tebbutt, Christophe Tournigand, Eric Van Cutsem, Aimery de Gramont, John R. Zalcberg, Marc Buyse
Journal: JAMA Network Open (2019)

Tumor measurements can be used to estimate time to nadir and depth of nadir as potential surrogates for overall survival (OS).To assess time to nadir and depth of nadir as surrogates for OS in metastatic colorectal cancer.Pooled analysis of 20 randomized clinical trials within the Aide et Recherche en Cancerologie Digestive database, which contains academic and industry-sponsored trials, was conducted. Three sets of comparisons were performed: chemotherapy alone, antiangiogenic agents, and anti-epidermal growth factor receptor agents in first-line treatment for patients with metastatic colorectal cancer.Surrogacy of time to nadir and depth of nadir was assessed at the trial level based on joint modeling of relative tumor-size change vs baseline and OS. Treatment effects on time to nadir and on depth of nadir were defined in terms of between-arm differences in time to nadir and in depth of nadir, and both were assessed in linear regressions for their correlation with treatment effects (hazard ratios) on OS within each set. The strengths of association were quantified using sample-size-weighted coefficients of determination (R2), with values closer to 1.00 indicating stronger association. At the patient level, the correlation was assessed between modeled relative tumor-size change and OS.For 14 chemotherapy comparisons in 4289 patients, the R2 value was 0.63 (95% CI, 0.30-0.96) for the association between treatment effects on time to nadir and OS and 0.08 (95% CI, 0-0.37) for depth of nadir and OS. For 11 antiangiogenic agent comparisons (4854 patients), corresponding values of R2 were 0.25 (95% CI, 0-0.72) and 0.06 (95% CI, 0-0.35). For 8 anti-epidermal growth factor receptor comparisons (2684 patients), corresponding values of R2 were 0.24 (95% CI, 0-0.83) and 0.21 (95% CI, 0-0.78).In contrast with early reports favoring depth of response as a surrogate, these results suggest that neither time to nadir nor depth of nadir is an acceptable surrogate for OS in the first-line treatment of metastatic colorectal cancer.
Real-time use of artificial intelligence in the evaluation of cancer in Barrett’s oesophagus
Authors: Alanna Ebigbo, Robert Mendel, Andreas Probst, Johannes Manzeneder, Friederike Prinz, Luis A de Souza Jr., Joao Papa, Christoph Palm, Helmut Messmann
Journal: Gut (2019)

Based on previous work by our group with manual annotation of visible Barrett oesophagus (BE) cancer images, a real-time deep learning artificial intelligence (AI) system was developed. While an expert endoscopist conducts the endoscopic assessment of BE, our AI system captures random images from the real-time camera livestream and provides a global prediction (classification), as well as a dense prediction (segmentation) differentiating accurately between normal BE and early oesophageal adenocarcinoma (EAC). The AI system showed an accuracy of 89.9% on 14 cases with neoplastic BE.

This paper follows up on our prior publication on the application of AI and deep learning in the evaluation of BE.1 2 In our initial publications, we developed a computer-aided diagnosis (CAD) model and demonstrated promising performance scores in the classification and segmentation domains during BE assessment.1 2 However, these results were achieved on optimal endoscopic images, which may not mirror the real-life situation sufficiently. To enable the seamless integration of AI-based image classification into the clinical workflow, our previous system was developed further to increase the speed of image analysis for classification and the resolution of the dense prediction, which shows the color-coded spatial distribution of cancer probabilities.1 2 Still based on deep convolutional neural nets (CNNs) and a residual net (ResNet) architecture with DeepLab V.3+, a state-of-the-art encoder–decoder network was adapted.3 To transfer the endoscopic livestream to our AI system, a capture card (Avermedia, Taiwan) was plugged to the endoscopic monitor.

Online supplementary video 1 shows the setting of AI-based BE evaluation in the endoscopy room of the University Hospital Augsburg (figure 1). The AI prediction can be started at any time using either a button on the keyboard or a foot switch. The video clip shows examples of …
Impact of palliative care consultation on end-of-life care measures: A retrospective analysis of patients in the Oncology Care Model.
Authors: Alison Greidinger, Maria Vershvovsky, Evan Lapinsky, Alison Rhoades, Amy Leader, Vittorio Maio, Jared Minetola, Karen Walsh, Valerie Pracilio Csik, Ruben Rhoades
Journal: Journal of Clinical Oncology (2019)

45 Background: Despite a 2016 ASCO recommendation that patients with advanced cancer receive dedicated palliative care (PC) services, many patients are not referred and continue to receive chemotherapy and utilize high-acuity services near the end of life (EOL). Studies suggest that early PC involvement is associated with lower spending, acute care utilization, and chemotherapy administration at the EOL. The Sidney Kimmel Cancer Center participates in the Oncology Care Model (OCM), a CMS episode-based alternative payment model promoting high-value care. Using OCM-generated data, we evaluated the effect of PC visits on EOL outcomes. Methods: We identified OCM patients with episodes starting April 1, 2016-July 1, 2018 with GI and head &amp; neck malignancies who had died, and determined whether patients who saw a PC provider had greater documentation of a code status (CS) before death, as well as lower spending and utilization of chemotherapy or acute care in the last 30 days of life. CMS spending data and dates of death were derived from OCM quarterly feedback, while all other data was compiled via chart review. CS was recorded at the start of the episode and at the time of death. Results: The study included 126 patients (median age 66 years), of whom 38% had a PC visit. 24% had only an inpatient (IP) PC consult, 6% only an outpatient (OP) visit, and 9% both IP &amp; OP visits. More patients who saw PC had an initial CS documented (85%, vs 46% for no PC), and had a greater proportional increase in CS documentation before death (96% vs 53%). Despite similar rates at baseline, the final CS was significantly more likely to be “Do Not Resuscitate/Intubate” (DNR/DNI) among PC patients (79%, vs 28% for no PC). An initial CS of DNR/DNI was associated with lower mean ICU and total non-hospice spending in the last 30 days of life. Conclusions: This retrospective study in OCM patients found that PC intervention is associated with improved documentation of a CS and higher rates of DNR/DNI documentation before death. There is an association between an initial DNR/DNI CS and lower acute care spending. This data suggests a beneficial effect of early PC on utilization at the EOL in advanced cancer patients.
Mitochondrial ATP-Dependent Potassium Channels
Authors: YonggeLiu, ToshiakiSato, BrianO’Rourke, EduardoMarban
Journal: Circulation (1998)

Background—Brief interruptions of coronary blood flow paradoxically protect the heart from subsequent prolonged ischemia. The basis of such endogenous cardioprotection, known as “ischemic preconditioning,” remains uncertain. Pharmacological evidence has implicated ATP-dependent potassium (KATP) channels in the mechanism of preconditioning; however, the effects of sarcolemmal KATP channels on excitability cannot account for the protection. Methods and Results—We simultaneously measured flavoprotein fluorescence, an index of mitochondrial redox state, and sarcolemmal KATP currents in intact rabbit ventricular myocytes. Our results show that diazoxide, a KATP channel opener, selectively activates mitochondrial KATP channels. Diazoxide induced reversible oxidation of flavoproteins with an EC50 of 27 μmol/L but did not activate sarcolemmal KATP channels. The subcellular site of diazoxide action is further localized to mitochondria by confocal imaging of fluorescence arising from flavoproteins and tetramethylrh...
The EAACI‐AAAAI‐WAO Junior Members’ joint survey: A worldwide snapshot of Allergy and Clinical Immunology specialty
Authors: Marco Caminati, Darío Antolín‐Amérigo, Matteo Bonini, Becky Buelow, Vanessa Bundy, Mariana Couto, Razvigor Darlenski, Filippo Fassio, Brian Kelly, Christina Kwong, Alexandra Santos, Olympia Tsilochristou, Luciana Kase Tanno
Journal: Allergy (2019)

Education and training in Allergy and Clinical Immunology (A/I) are characterized by a great variability worldwide. However, objective and worldwide data regarding this topic are lacking.To investigate personal information, education, and involvement in scientific societies of juniors engaged in A/I field, a questionnaire was developed by representatives from the JMs' boards of the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the World Allergy Organization (WAO).A total of 543 questionnaires were collected from 76 regions of all continents. The geographic distribution of responders was as follows: Africa-Middle East 3.0%, Asia-Pacific 21.4%, Europe 48.2%, Latin America 12.1%, and North America 15.3%. 59.0% of responders declared that A/I is recognized as a separate specialty in their country, Europe mostly accounting for that proportion. Primary interest in the field represents the main motivation for choosing A/I specialty. Concerning involvement in scientific societies, 41.1% of responders ever attended an EAACI Congress, 20.6% an AAAAI Congress, and 20.4% a WAO Congress. According to 40.3% of responders, scientific societies do not provide enough opportunities for young members, and 96.4% believes in a more intensive cooperation between the A/I Societies.The survey provides the first worldwide perspective about A/I specialty. It represents the first ever example of a structured collaboration between the junior members (JMs) of the three main A/I Societies. The findings suggest the need for harmonization, at least in terms of training and formation in the field of A/I worldwide.
Abstract 12074: Door-To-Targeted Temperature Management Initiation Time and Outcomes in Out-Of-Hospital Cardiac Arrest: Insights From the CCC Trial
Authors: Dylan Stanger, Takahisa Kawano, Navraj Malhi, Brian Grunau, John Tallon, Graham C Wong, James Christenson, Christopher B Fordyce
Journal: Circulation (2018)

Introduction: Targeted temperature management (TTM) is a recommended treatment modality to improve neurologic outcomes in patients with out-of-hospital cardiac arrest (OHCA). The impact of the dura...
Abstract 16459: A Novel Hydrogen Sulfide Donor, JK1, Preserves Left Ventricular Ejection Fraction and Improves Hemodynamics in the Setting of Heart Failure
Authors: Zhen Li, Chelsea L Organ, Craig M Zibilich, Jianming Kang, Ming Xian, David J Lefer
Journal: Circulation (2017)

Background and Hypothesis: Hydrogen sulfide (H2S) protects against heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One limitation in the...
Brexit: European health experts emphasise dangers to patient safety of no deal
Authors: Rory Watson
Journal: BMJ (2019)

A no deal Brexit would have disastrous consequences for patients and public health services on both sides of the English Channel, a wide ranging, informal group of health professionals has warned.

They pointed to problems in the supply of drugs and medical devices, damage to EU-wide medical collaboration and research, disruption to training and to mutual recognition of qualifications, and weakening of European coordination on pandemic preparedness and tackling antimicrobial resistance. UK nationals would no longer be able to use the European health insurance card on the continent, nor EU citizens in the UK.

The meeting in the European parliament on 12 September brought together representatives from the …
Myeloid cell–synthesized coagulation factor X dampens antitumor immunity
Authors: Claudine Graf, Petra Wilgenbus, Sven Pagel, Jennifer Pott, Federico Marini, Sabine Reyda, Maki Kitano, Stephan Macher-Göppinger, Hartmut Weiler, Wolfram Ruf
Journal: Science Immunology (2019)

Immune evasion in the tumor microenvironment (TME) is a crucial barrier for effective cancer therapy, and plasticity of innate immune cells may contribute to failures of targeted immunotherapies. Here, we show that rivaroxaban, a direct inhibitor of activated coagulation factor X (FX), promotes antitumor immunity by enhancing infiltration of dendritic cells and cytotoxic T cells at the tumor site. Profiling FX expression in the TME identifies monocytes and macrophages as crucial sources of extravascular FX. By generating mice with immune cells lacking the ability to produce FX, we show that myeloid cell-derived FX plays a pivotal role in promoting tumor immune evasion. In mouse models of cancer, we report that the efficacy of rivaroxaban is comparable with anti-programmed cell death ligand 1 (PD-L1) therapy and that rivaroxaban synergizes with anti-PD-L1 in improving antitumor immunity. Mechanistically, we demonstrate that FXa promotes immune evasion by signaling through protease-activated receptor 2 and that rivaroxaban specifically targets this cell-autonomous signaling pathway to reprogram tumor-associated macrophages. Collectively, our results have uncovered the importance of FX produced in the TME as a regulator of immune cell activation and suggest translational potential of direct oral anticoagulants to remove persisting roadblocks for immunotherapy and provide extravascular benefits in other diseases.
Sequential screening for lung cancer in a high-risk group: randomised controlled trial
Authors: Stephen G. Spiro, Pallav L. Shah, Robert C. Rintoul, Jeremy George, Samuel Janes, Matthew Callister, Marco Novelli, Penny Shaw, Gabrijela Kocjan, Chris Griffiths, Mary Falzon, Richard Booton, Nicholas Magee, Michael Peake, Paul Dhillon, Kishore Sridharan, Andrew G. Nicholson, Simon Padley, Magali N. Taylor, Asia Ahmed, Jack Allen, Yenting Ngai, Nyasha Chinyanganya, Victoria Ashford-Turner, Sarah Lewis, Dahmane Oukrif, Pamela Rabbitts, Nicholas Counsell, Allan Hackshaw
Journal: European Respiratory Journal (2019)

Background Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. Methods LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). Results 1568 participants were randomised during 2007–2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75–1.95) or 0.82 (95% CI 0.52–1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. Conclusions Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.
Retrospective Analysis of 111 Cases of Multiple Myeloma Treated with Autologous Hematopoietic Stem Cell Transplantation
Authors: Chengcheng Fu, Yun Xu, Juan Wang, Jin Zhou, Ling Ma, Shuang Yan, Panfeng Wang, Ying Yao, Song Jin, Lingzhi Yan, Depei Wu
Journal: Blood (2016)
Survival by Race and Ethnicity in Pediatric and Adolescent Patients With Hodgkin Lymphoma: A Children’s Oncology Group Study
Authors: Justine M. Kahn, Kara M. Kelly, Qinglin Pei, Rizvan Bush, Debra L. Friedman, Frank G. Keller, Smita Bhatia, Tara O. Henderson, Cindy L. Schwartz, Sharon M. Castellino
Journal: Journal of Clinical Oncology (2019)

Population-based studies of children and adolescents with Hodgkin lymphoma (HL) report a survival disadvantage in nonwhite-non-Hispanic black (NHB) and Hispanic-patients. Whether disparities persist after adjustment for clinical and treatment-related variables is unknown. We examined survival by race/ethnicity in children receiving risk-based, response-adapted, combined-modality therapy for HL in contemporary Children's Oncology Group trials.This pooled analysis used individual-level data from 1,605 patients (younger than age 1 to 21 years) enrolled in phase III trials for low-risk (AHOD0431), intermediate-risk (AHOD0031), and high-risk (AHOD0831) HL from 2002 to 2012. Event-free survival (EFS) and overall survival (OS) were compared between non-Hispanic white (NHW) and nonwhite patients. Cox proportional hazards for survival were estimated for both de novo and relapsed HL, adjusting for demographics, disease characteristics, and therapy.At median follow up of 6.9 years, cumulative incidence of relapse was 17%. Unadjusted 5-year EFS and OS were 83% (SE, 1.2%) and 97% (SE, < 1%), respectively. Neither differed by race/ethnicity. In multivariable analyses for OS, nonwhite patients had a 1.88× higher hazard of death (95% CI, 1.1 to 3.3). Five-year postrelapse survival probabilities by race were as follows: NHW, 90%; NHB, 66%; and Hispanic, 80% (P < .01). Compared with NHW, Hispanic and NHB children had 2.7-fold (95% CI, 1.2 to 6.2) and 3.5-fold (95% CI, 1.5 to 8.2) higher hazard of postrelapse mortality, respectively.In patients who were treated for de novo HL in contemporary Children's Oncology Group trials, EFS did not differ by race/ethnicity; however, adjusted OS was significantly worse in nonwhite patients, a finding driven by increased postrelapse mortality in this population. Additional studies examining treatment and survival disparities after relapse are warranted.
Angiopoietin-like 4 binds neuropilins and cooperates with VEGF to induce diabetic macular edema
Authors: Akrit Sodhi, Tao Ma, Deepak Menon, Monika Deshpande, Kathleen Jee, Aumreetam Dinabandhu, Jordan Vancel, Daoyuan Lu, Silvia Montaner
Journal: Journal of Clinical Investigation (2019)

The majority of patients with diabetic macular edema (DME), the most common cause of vision loss in working-age Americans, do not respond adequately to current therapies targeting VEGFA. Here, we show that expression of angiopoietin-like 4 (ANGPTL4), a HIF-1-regulated gene product, is increased in the eyes of diabetic mice and patients with DME. We observed that ANGPTL4 and VEGF act synergistically to destabilize the retinal vascular barrier. Interestingly, while ANGPTL4 modestly enhanced tyrosine phosphorylation of VEGF receptor 2, promotion of vascular permeability by ANGPTL4 was independent of this receptor. Instead, we found that ANGPTL4 binds directly to neuropilin 1 (NRP1) and NRP2 on endothelial cells (ECs), leading to rapid activation of the RhoA/ROCK signaling pathway and breakdown of EC-EC junctions. Treatment with a soluble fragment of NRP1 (sNRP1) prevented ANGPTL4 from binding to NRP1 and blocked ANGPTL4-induced activation of RhoA as well as EC permeability in vitro and retinal vascular leakage in diabetic animals in vivo. In addition, sNRP1 reduced the stimulation of EC permeability by aqueous fluid from patients with DME. Collectively, these data identify the ANGPTL4/NRP/RhoA pathway as a therapeutic target for the treatment of DME.