tbuckley/cabot-search huggingface dataset:
Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy
Authors: Xuan Cao, Jaron Castillo Sanchez, Aumreetam Dinabandhu, Chuanyu Guo, Tapan P. Patel, Zhiyong Yang, Ming-Wen Hu, Lijun Chen, Yuefan Wang, Danyal Malik, Kathleen Jee, Yassine J. Daoud, James T. Handa, Hui Zhang, Jiang Qian, Silvia Montaner, Akrit Sodhi
Journal: Journal of Clinical Investigation (2021)

BackgroundTo reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear.MethodsEyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients' response to treatment.ResultsAt the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients' response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV.FundingThis work was supported by the National Eye Institute, National Institutes of Health grants R01EY029750, R01EY025705, and R01 EY27961; the Research to Prevent Blindness, Inc.; the Alcon Research Institute; and Johns Hopkins University through the Robert Bond Welch and Branna and Irving Sisenwein professorships in ophthalmology.ConclusionAqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.
43P Assessment of biomarker kinetics for ADG106 (anti-CD137 agonist) as monotherapy or combined with toripalimab
Authors: H. Zhao, S. Zheng, G. Liu, Y. Ma, K. She, M. Chen, B. Li, X. Wang, L. Zhu, Y. Zhang, H. Gong, P. Luo, L. Zhang
Journal: Annals of Oncology (2021)
13. Older Adults: <i>Standards of Medical Care in Diabetes—2022</i>
Journal: Diabetes Care (2021)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
The BMJ Interview: in conversation with Fiona Godlee
Authors: Helen Macdonald
Journal: BMJ (2021)

As she steps down after 16 years as The BMJ’s editor in chief, find out more about Fiona Godlee, a mission driven woman who has brought ideas and people together in the public interest. You can listen to Fiona talking to <b>Helen Macdonald</b> at https://bit.ly/BMJInterview
An Artificial Intelligence–Based Chest X-ray Model on Human Nodule Detection Accuracy From a Multicenter Study
Authors: Fatemeh Homayounieh, Subba Digumarthy, Shadi Ebrahimian, Johannes Rueckel, Boj Friedrich Hoppe, Bastian Oliver Sabel, Sailesh Conjeti, Karsten Ridder, Markus Sistermanns, Lei Wang, Alexander Preuhs, Florin Ghesu, Awais Mansoor, Mateen Moghbel, Ariel Botwin, Ramandeep Singh, Samuel Cartmell, John Patti, Christian Huemmer, Andreas Fieselmann, Clemens Joerger, Negar Mirshahzadeh, Victorine Muse, Mannudeep Kalra
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Most early lung cancers present as pulmonary nodules on imaging, but these can be easily missed on chest radiographs. <h3>Objective</h3> To assess if a novel artificial intelligence (AI) algorithm can help detect pulmonary nodules on radiographs at different levels of detection difficulty. <h3>Design, Setting, and Participants</h3> This diagnostic study included 100 posteroanterior chest radiograph images taken between 2000 and 2010 of adult patients from an ambulatory health care center in Germany and a lung image database in the US. Included images were selected to represent nodules with different levels of detection difficulties (from easy to difficult), and comprised both normal and nonnormal control. <h3>Exposures</h3> All images were processed with a novel AI algorithm, the AI Rad Companion Chest X-ray. Two thoracic radiologists established the ground truth and 9 test radiologists from Germany and the US independently reviewed all images in 2 sessions (unaided and AI-aided mode) with at least a 1-month washout period. <h3>Main Outcomes and Measures</h3> Each test radiologist recorded the presence of 5 findings (pulmonary nodules, atelectasis, consolidation, pneumothorax, and pleural effusion) and their level of confidence for detecting the individual finding on a scale of 1 to 10 (1 representing lowest confidence; 10, highest confidence). The analyzed metrics for nodules included sensitivity, specificity, accuracy, and receiver operating characteristics curve area under the curve (AUC). <h3>Results</h3> Images from 100 patients were included, with a mean (SD) age of 55 (20) years and including 64 men and 36 women. Mean detection accuracy across the 9 radiologists improved by 6.4% (95% CI, 2.3% to 10.6%) with AI-aided interpretation compared with unaided interpretation. Partial AUCs within the effective interval range of 0 to 0.2 false positive rate improved by 5.6% (95% CI, −1.4% to 12.0%) with AI-aided interpretation. Junior radiologists saw greater improvement in sensitivity for nodule detection with AI-aided interpretation as compared with their senior counterparts (12%; 95% CI, 4% to 19% vs 9%; 95% CI, 1% to 17%) while senior radiologists experienced similar improvement in specificity (4%; 95% CI, −2% to 9%) as compared with junior radiologists (4%; 95% CI, −3% to 5%). <h3>Conclusions and Relevance</h3> In this diagnostic study, an AI algorithm was associated with improved detection of pulmonary nodules on chest radiographs compared with unaided interpretation for different levels of detection difficulty and for readers with different experience.
QOLP-36. PATTERN OF CARE OF BRAIN TUMOR PATIENTS IN THE LAST MONTHS OF LIFE: ANALYSIS OF A COHORT OF 3045 PATIENTS IN THE LAZIO REGION IN THE LAST 10 YEARS
Authors: Andrea Pace, Valeria Belleudi, Luigi Pinarelli, Veronica Villani, Francesca poggi, Dario Benincasa, Marina Davoli
Journal: Neuro-Oncology (2021)

Abstract The final days of life of Brain Tumor patients (BT) present special challenges and often palliative care approach is underutilyzed. Several studies reported that BT patients in the last months of life receive frequent hospital readmissions and ER accesses as result of bad quality of End of Life care. Early integration of pallative care has been demonstrated to improve quality of care in advanced stage of disease and quality of death in cancer patients. With the aim to evaluate pattern of treatment and the rate of hospital readmission in the last months of life, we retrospectively analyzed a consecutive serie of BT patients discharged after a diagnosis of BT. METHODS: Data regarding hospital readmission and treatment received in the last two months of life were collected from the Lazio Region Healthcare database. Adult patients discharged with diagnosis ICD-9 191.* between 1/1/2010 until 31/12/2019, were included in this study. RESULTS: 6672 patients were identified and 3045 death before 31/12/2019 were included (median age 67 y;M1700). In the last month of life 42.6% received hospital reamission (4.6% intensive care unit) and 37.9% had ER accesses. 24.5% received chemotherapy and 12.1% radiotherapy. In the last 30 days 33% were readmitted in hospital and 24.2% were admitted in ER. 11.7% were treated with chemotherapy and 6% with radiotherapy. CONCLUSION: Strategies to improve quality of care at the end of life and to decrease rehospitalization and futile treatments are becoming increasingly important to improve quality of death and to reduce costs of Healthcare System.
Abstract 14505: Determinants of Stabilization for Out-of-Hospital Cardiac Arrest Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation
Authors: Ruben Crespo, Marinos Kosmopoulos, Demitris Yannopolous, Jason Bartos
Journal: Circulation (2021)

Introduction: Sudden cardiac arrest causes approximately 400,000 deaths in the United States per year. Extracorporeal membrane oxygenation (ECMO), in conjunction with coronary interventions, was shown to improve survival for patients with refractory shockable rhythms in the ARREST trial. However, it remains unclear which parts of the protocol are critical for hemodynamic stabilization in these patients. Therefore, this study aims to assess patient status through each step of the ARREST trial protocol. Methods: Retrospective assessment was performed in 185 adults with refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest transported for ECPR. Continuous variables were compared using parametric or non-parametric testing when normality was not met. Chi-square was used to compare categorical values and linear regression models to compare associations between survival and angiographic characteristics. Results: Distribution data showed 32% of patients achieved ROSC prior to extracorporeal membrane oxygenation or coronary intervention, though they had ongoing cardiogenic shock. ECMO provided hemodynamic stabilization with an organized cardiac rhythm in 31% of patients prior to coronary intervention. ECMO and coronary revascularization was required for hemodynamic stabilization and development of an organized cardiac rhythm in 30% of patients. The remaining 7% of patients failed to achieve ROSC despite ECMO, revascularization, and medical therapy. The angiographic profile from each of these groups was evaluated and showed that 63% of all patients had obstructive CAD including 48% of patients that arrived with ROSC and cardiogenic shock, 71% of patients that stabilized with ECMO alone, and 100% of patients that achieved ROSC after coronary interventions (p&lt;0.01). Conclusions: Coronary revascularization is not required for stabilization of most patients. However, the impact of coronary artery disease on recovery potential is not known.
Periodic Repolarization Dynamics Identifies ICD Responders in Nonischemic Cardiomyopathy: A DANISH Substudy
Authors: Rune Boas, Nikolay Sappler, Lukas von Stülpnagel, Mathias Klemm, Ulrik Dixen, Jens Jakob Thune, Steen Pehrson, Lars Køber, Jens C. Nielsen, Lars Videbæk, Jens Haarbo, Eva Korup, Niels Eske Bruun, Axel Brandes, Hans Eiskjær, Anna M. Thøgersen, Berit T. Philbert, Jesper Hastrup Svendsen, Jacob Tfelt-Hansen, Axel Bauer, Konstantinos D. Rizas
Journal: Circulation (2021)

Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation.We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg2 as an exploratory cut-off value for ICD implantation.A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group (P=0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio [HR], 1.28 [95% CI, 1.09-1.50] per SD increase; P=0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 [95% CI, 1.25-1.81]; P<0.001) but not in the ICD group (HR, 1.04 [95% CI, 0.83-1.54]; P=0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality (P=0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg2 (HR, 0.54 [95% CI, 0.34-0.84]; P=0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg2 (HR, 1.17 [95% CI, 0.77-1.78]; P=0.46; P for interaction=0.01).Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.
Persistence of the neutralizing antibody response after SARS-CoV-2 infection
Authors: Sang-Mu Shim, Jun-Won Kim, Sunhee Jung, Yujung Jung, Hye-Min Woo, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee
Journal: Clinical Microbiology and Infection (2021)

Neutralizing antibodies are among the factors used to measure an individual's immune status for the control of infectious diseases. We aimed to confirm the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody levels in patients who had recovered from coronavirus disease 2019 (COVID-19).Plasma donors in South Korea who had completely recovered from SARS-CoV-2 infection had follow-up testing to determine the persistence of neutralizing antibodies using a plaque-reduction neutralization test and ELISA.Of the 111 participants-aged 20-29 years, 37/111 (33.3%); 30-39 years, 17/111 (15.3%); 40-49 years, 23/111 (20.7%); 50-59 years, 21/111 (18.9%); 60-65 years, 13/111 (11.7%); male, 43/111 (38.7%); female, 68/111 (61.3%)-66.1% still had neutralizing antibodies approximately 9 months (range 255-302 days) after confirmation of the diagnosis.In this study we analysed the titre of neutralizing antibodies associated with predicting immune status in individuals with natural infection. Information about the persistence and change in levels of neutralizing antibodies against SARS-CoV-2 can be utilized to provide evidence for developing vaccination schedules for individuals with previous infection.
Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.
Authors: Milou A M Stals, Toshihiko Takada, Noémie Kraaijpoel, Nick van Es, Harry R Büller, D Mark Courtney, Yonathan Freund, Javier Galipienzo, Grégoire Le Gal, Waleed Ghanima, Menno V Huisman, Jeffrey A Kline, Karel G M Moons, Sameer Parpia, Arnaud Perrier, Marc Righini, Helia Robert-Ebadi, Pierre-Marie Roy, Maarten van Smeden, Phil S Wells, Kerstin de Wit, Geert-Jan Geersing, Frederikus A Klok
Journal: Annals of Internal Medicine (2022)

How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown.To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups.MEDLINE from 1 January 1995 until 1 January 2021.16 studies assessing at least 1 diagnostic strategy.Individual-patient data from 20 553 patients.Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups.Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds.Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds.Dutch Research Council. (PROSPERO: CRD42018089366).
Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program
Authors: Amer M. Zeidan, Aref Al-Kali, Uma Borate, Thomas Cluzeau, Amy E. DeZern, Jordi Esteve, Aristoteles Giagounidis, Krissy Kobata, Roger Lyons, Uwe Platzbecker, David A. Sallman, Valeria Santini, Guillermo Sanz, Mikkael A. Sekeres, Andrew H. Wei, Zhijian Xiao, Marlies Van Hoef, Claire Nourry-Boulot, Islam Sadek, Bourras-Rezki Bengoudifa, Carolin Sachs, John Sabo, Guillermo Garcia-Manero
Journal: Blood (2021)
Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome
Authors: David S. Perlin, Garry A. Neil, Colleen Anderson, Inbal Zafir-Lavie, Shane Raines, Carl F. Ware, H. Jeffrey Wilkins
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune response, which can result in cytokine-release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT-neutralization therapy.METHODSThis randomized, double-blind, multicenter, proof-of-concept trial enrolled adults hospitalized with COVID-19-associated pneumonia and mild to moderate ARDS. Patients received standard of care plus a single dose of a human LIGHT-neutralizing antibody (CERC-002) or placebo. The primary endpoint was the proportion of patients receiving CERC-002 who remained alive and free of respiratory failure through day 28. Safety was assessed via adverse event monitoring.RESULTSFor most of the 83 enrolled patients, standard of care included systemic corticosteroids (88.0%) or remdesivir (57.8%). A higher proportion of patients remained alive and free of respiratory failure through day 28 after receiving CERC-002 (83.9%) versus placebo (64.5%; P = 0.044), including in patients 60 years of age or older (76.5% vs. 47.1%, respectively; P = 0.042). Mortality rates were 7.7% (CERC-002) and 14.3% (placebo) on day 28 and 10.8% and 22.5%, respectively, on day 60. Treatment-emergent adverse events were less frequent with CERC-002 than placebo.CONCLUSIONFor patients with COVID-19-associated ARDS, adding CERC-002 to standard-of-care treatment reduces LIGHT levels and might reduce the risk of respiratory failure and death.TRIAL REGISTRATIONClinicalTrials.gov NCT04412057.FUNDINGAvalo Therapeutics.
58P Validation of the Achilles VELOS process 2 manufacturing platform for the treatment of solid cancer: GMP scale runs generate a significant dose boost of highly potent clonal neoantigen reactive T-cells
Authors: E.R. Samuel, E. Rologi, H. Fraser, M. Sassi, M. Pruchniak, E. Kotsiou, J. Robinson, K. Benzekhroufa, L. Goodsell, C. Carolan, M. Saggese, M. Grant, B. Samways, P. Kotecha, A. Schmitt, D. Lawrence, M. Forster, S. Turajlic, M. Lowdell, S. Quezada
Journal: Annals of Oncology (2021)
Homing in on haemoglobinopathies
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2021)

In November, 2021, the UK All-Party Parliamentary Group (APPG) on Sickle Cell and Thalassaemia published an alarming report on care failures and avoidable deaths among patients with sickle-cell disease. Particularly within non-specialist care such as general hospital wards and emergency departments, the inquiry revealed inconsistent standards of care between regions, failures to comply with national care standards, poor continuity of care, disrespect, and racism.
Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia
Authors: Lian Deng, Yuwen Pan, Yinan Wang, Hao Chen, Kai Yuan, Sihan Chen, Dongsheng Lu, Yan Lu, Siti Shuhada Mokhtar, Thuhairah Abdul Rahman, Boon-Peng Hoh, Shuhua Xu
Journal: Molecular Biology and Evolution (2021)

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.