tbuckley/cabot-search huggingface dataset:
Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance
Authors: Vincent L. Aengevaeren, Aaron L. Baggish, Eugene H. Chung, Keith George, Øyunn Kleiven, Alma M.A. Mingels, Stein Ørn, Rob E. Shave, Paul D. Thompson, Thijs M.H. Eijsvogels
Journal: Circulation (2021)

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.
115TiP Stereotactic body radiotherapy (SBRT) plus anlotinib with or without toripalimab in driver mutation-negative non-small cell lung cancer (NSCLC) patients with untreated brain oligometastatic metastases: A prospective, single-center, phase Ib study
Authors: G. Han, J. Bi, J. Ma, M. Yuan, Y. Li, G. Pi, L. Guo, Y. Li, D. Hu
Journal: Annals of Oncology (2021)
Maternal Phthalates Exposure and Blood Pressure during and after Pregnancy in the PROGRESS Study
Authors: Haotian Wu, Allison Kupsco, Allan Just, Antonia M. Calafat, Emily Oken, Joseph M. Braun, Alison P. Sanders, Adriana Mercado-Garcia, Alejandra Cantoral, Ivan Pantic, Martha M. Téllez-Rojo, Robert O. Wright, Andrea A. Baccarelli, Andrea L. Deierlein
Journal: Environmental Health Perspectives (2021)

Phthalate exposure is ubiquitous and may affect biological pathways related to regulators of blood pressure. Given the profound changes in vasculature during pregnancy, pregnant women may be particularly susceptible to the potential effects of phthalates on blood pressure. We examined associations of phthalate exposure during pregnancy with maternal blood pressure trajectories from mid-pregnancy through 72 months postpartum. Women with singleton pregnancies delivering a live birth in Mexico City were enrolled during the second trimester (n=892). Spot urine samples from the second and third trimesters were analyzed for 15 phthalate metabolites. Blood pressure and covariate data were collected over nine visits through 72 months postpartum. We used linear, logistic, and linear mixed models; latent class growth models (LCGMs); and Bayesian kernel machine regression to estimate the relationship of urinary phthalate biomarkers with maternal blood pressure. As a joint mixture, phthalate biomarker concentrations during pregnancy were associated with higher blood pressure rise during mid-to-late gestation. With respect to individual biomarkers, second trimester concentrations of monobenzyl phthalate (MBzP) and di(2-ethylhexyl) phthalate biomarkers (ΣDEHP) were associated with higher third trimester blood pressure. Two trajectory classes were identified by LCGM, characterized by increasing blood pressure through 72 months postpartum ("increase-increase") or decreased blood pressure through 18 months postpartum with a gradual increase thereafter ("decrease-increase"). Increasing exposure to phthalate mixtures during pregnancy was associated with higher odds of being in the increase-increase class. Similar associations were observed for mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and dibutyl phthalate (ΣDBP) biomarkers. When specific time periods were examined, we observed specific temporal relationships were observed for ΣDEHP, MECPTP, MBzP, and ΣDBP. In our cohort of pregnant women from Mexico City, exposure to phthalates and phthalate biomarkers was associated with higher blood pressure during late pregnancy, as well as with long-term changes in blood pressure trajectories. https://doi.org/10.1289/EHP8562.
As Maintenance Therapy, Olaparib's Benefits Continue
Journal: Cancer Discovery (2021)

Abstract A 5-year follow-up of patients in the ongoing SOLO1 trial showed that patients with advanced BRCA-mutated ovarian cancer who had finished platinum-based chemotherapy had a significantly longer median progression-free survival when they received 2 years of olaparib as a maintenance therapy instead of placebo—56 months versus 13.8 months, respectively.
Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma
Authors: Amani Makkouk, Xue (Cher) Yang, Taylor Barca, Anthony Lucas, Mustafa Turkoz, Jonathan T S Wong, Kevin P Nishimoto, Mary M Brodey, Maryam Tabrizizad, Smitha R Y Gundurao, Lu Bai, Arun Bhat, Zili An, Stewart Abbot, Daulet Satpayev, Blake T Aftab, Marissa Herrman
Journal: Journal for ImmunoTherapy of Cancer (2021)

Glypican-3 (GPC-3) is an oncofetal protein that is highly expressed in various solid tumors, but rarely expressed in healthy adult tissues and represents a rational target of particular relevance in hepatocellular carcinoma (HCC). Autologous chimeric antigen receptor (CAR) αβ T cell therapies have established significant clinical benefit in hematologic malignancies, although efficacy in solid tumors has been limited due to several challenges including T cell homing, target antigen heterogeneity, and immunosuppressive tumor microenvironments. Gamma delta (γδ) T cells are highly cytolytic effectors that can recognize and kill tumor cells through major histocompatibility complex (MHC)-independent antigens upregulated under stress. The Vδ1 subset is preferentially localized in peripheral tissue and engineering with CARs to further enhance intrinsic antitumor activity represents an attractive approach to overcome challenges for conventional T cell therapies in solid tumors. Allogeneic Vδ1 CAR T cell therapy may also overcome other hurdles faced by allogeneic αβ T cell therapy, including graft-versus-host disease (GvHD).We developed the first example of allogeneic CAR Vδ1 T cells that have been expanded from peripheral blood mononuclear cells (PBMCs) and genetically modified to express a 4-1BB/CD3z CAR against GPC-3. The CAR construct (GPC-3.CAR/secreted interleukin-15 (sIL)-15) additionally encodes a constitutively-secreted form of IL-15, which we hypothesized could sustain proliferation and antitumor activity of intratumoral Vδ1 T cells expressing GPC-3.CAR.GPC-3.CAR/sIL-15 Vδ1 T cells expanded from PBMCs on average 20,000-fold and routinely reached >80% purity. Expanded Vδ1 T cells showed a primarily naïve-like memory phenotype with limited exhaustion marker expression and displayed robust in vitro proliferation, cytokine production, and cytotoxic activity against HCC cell lines expressing low (PLC/PRF/5) and high (HepG2) GPC-3 levels. In a subcutaneous HepG2 mouse model in immunodeficient NSG mice, GPC-3.CAR/sIL-15 Vδ1 T cells primarily accumulated and proliferated in the tumor, and a single dose efficiently controlled tumor growth without evidence of xenogeneic GvHD. Importantly, compared with GPC-3.CAR Vδ1 T cells lacking sIL-15, GPC-3.CAR/sIL-15 Vδ1 T cells displayed greater proliferation and resulted in enhanced therapeutic activity.Expanded Vδ1 T cells engineered with a GPC-3 CAR and sIL-15 represent a promising platform warranting further clinical evaluation as an off-the-shelf treatment of HCC and potentially other GPC-3-expressing solid tumors.
91P Phase I dose escalation of IMC-C103C, a CD3×MAGE-A4 T-cell receptor (TCR) bispecific protein
Authors: D. Davar, R.F. Sweis, G. Blumenschein, R. Gutierrez, I. Melero, H.A. Chen, F. Thistlethwaite, K.N. Moore, N.H. Segal, E. Garralda, B. Wilky, H-T. Arkenau, T.R.J. Evans, M.L. Johnson, M. Dar, C. Holland, S. Marshall, S. Stanhope, P. Kirk, J.S. Lopez
Journal: Annals of Oncology (2021)
Letter to the editor: Increase of influenza vaccination coverage rates during the COVID-19 pandemic and implications for the upcoming influenza season in northern hemisphere countries and Australia
Authors: Marco Del Riccio, Bruno Lina, Saverio Caini, Lisa Staadegaard, Sytske Wiegersma, Jan Kynčl, Béhazine Combadière, Chandini Raina MacIntyre, John Paget
Journal: Eurosurveillance (2021)

Preview this article: Letter to the editor: Increase of influenza vaccination coverage rates during the COVID-19 pandemic and implications for the upcoming influenza season in northern hemisphere countries and Australia, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/26/50/eurosurv-26-50-9-1.gif
In afebrile men with UTIs, 7 d of ciprofloxacin or trimethoprim–sulfamethoxazole was noninferior to 14 d
Authors: Jade M. Teakell, Donald A. Molony
Journal: Annals of Internal Medicine (2021)

Source Citation Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 days of antibiotic therapy on resolution of symptoms among afebrile men with urinary tract infection: a randomized clinical trial. JAMA. 2021;326:324-31. 34313686
Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer
Authors: Michela Masetti, Roberta Carriero, Federica Portale, Giulia Marelli, Nicolò Morina, Marta Pandini, Marta Iovino, Bianca Partini, Marco Erreni, Andrea Ponzetta, Elena Magrini, Piergiuseppe Colombo, Grazia Elefante, Federico Simone Colombo, Joke M.M. den Haan, Clelia Peano, Javier Cibella, Alberto Termanini, Paolo Kunderfranco, Jolanda Brummelman, Matthew Wai Heng Chung, Massimo Lazzeri, Rodolfo Hurle, Paolo Casale, Enrico Lugli, Ronald A. DePinho, Subhankar Mukhopadhyay, Siamon Gordon, Diletta Di Mitri
Journal: The Journal of Experimental Medicine (2021)

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell–derived IL-1β enhances Marco expression on macrophages, and reciprocally, cancer cell migration is promoted by CCL6 released by lipid-loaded TAMs. Moreover, administration of a high-fat diet to tumor-bearing mice raises the abundance of lipid-loaded TAMs. Finally, targeting lipid accumulation by Marco blockade hinders tumor growth and invasiveness and improves the efficacy of chemotherapy in models of PCa, pointing to combinatorial strategies that may influence patient outcomes.
Multimodal imaging for detection and segmentation of Barrett’s esophagus-related neoplasia using artificial intelligence
Authors: Alanna Ebigbo, Robert Mendel, Andreas Probst, Michael Meinikheim, Michael F. Byrne, Helmut Messmann, Christoph Palm
Journal: Endoscopy (2021)

The early diagnosis of cancer in Barrett's esophagus is crucial for improving the prognosis. However, identifying Barrett's esophagus-related neoplasia (BERN) is challenging, even for experts [1]. Four-quadrant biopsies may improve the detection of neoplasia, but they can be associated with sampling errors. The application of artificial intelligence (AI) to the assessment of Barrett's esophagus could improve the diagnosis of BERN, and this has been demonstrated in both preclinical and clinical studies [2] [3].
Stratified Care vs Stepped Care for Depression
Authors: Jaime Delgadillo, Shehzad Ali, Kieran Fleck, Charlotte Agnew, Amy Southgate, Laura Parkhouse, Zachary D. Cohen, Robert J. DeRubeis, Michael Barkham
Journal: JAMA Psychiatry (2021)

Depression is a major cause of disability worldwide. Although empirically supported treatments are available, there is scarce evidence on how to effectively personalize psychological treatment selection.To compare the clinical effectiveness and cost-effectiveness of 2 treatment selection strategies: stepped care and stratified care.This multisite, cluster randomized clinical trial recruited participants from the English National Health Service from July 5, 2018, to February 1, 2019. Thirty clinicians working across 4 psychological therapy services were randomly assigned to provide stratified (n = 15) or stepped (n = 15) care. In stepped care, patients sequentially access low-intensity guided self-help followed by high-intensity psychotherapy. In stratified care, patients are matched with either low- or high-intensity treatments at initial assessment. Data were analyzed from May 18, 2020, to October 13, 2021, using intention-to-treat principles.All clinicians used the same interview schedule to conduct initial assessments with patients seeking psychological treatment for common mental disorders, but those in the stratified care group received a personalized treatment recommendation for each patient generated by a machine learning algorithm. Eligible patients received either stratified or stepped care (ie, treatment as usual).The preregistered outcome was posttreatment reliable and clinically significant improvement (RCSI) of depression symptoms (measured using the 9-item Patient Health Questionnaire). The RCSI outcome was compared between groups using logistic regression adjusted for baseline severity. Cost-effectiveness analyses compared incremental costs and health outcomes of the 2 treatment pathways.A total of 951 patients were included (618 women among 950 with data available [65.1%]; mean [SD] age, 38.27 [14.53] years). The proportion of cases of RCSI was significantly higher in the stratified care arm compared with the stepped care arm (264 of 505 [52.3%] vs 134 of 297 [45.1%]; odds ratio, 1.40 [95% CI, 1.04-1.87]; P = .03). Stratified care was associated with a higher mean additional cost per patient (£104.5 [95% CI, £67.5-£141.6] [$139.83 (95% CI, $90.32-$189.48)]; P < .001) because more patients accessed high-intensity treatments (332 of 583 [56.9%] vs 107 of 368 [29.1%]; χ2 = 70.51; P < .001), but this additional cost resulted in an approximately 7% increase in the probability of RCSI.In this cluster randomized clinical trial of adults with common mental disorders, stratified care was efficacious and cost-effective for the treatment of depression symptoms compared with stepped care. Stratified care can improve depression treatment outcomes at a modest additional cost.isrctn.org Identifier: ISRCTN11106183.
Insights into clinical and diagnostic findings as well as treatment responses in patients with mucous membrane pemphigoid: A retrospective cohort study
Authors: Hanan Rashid, Joost M. Meijer, Maria C. Bolling, Gilles F.H. Diercks, Hendri H. Pas, Barbara Horváth
Journal: Journal of the American Academy of Dermatology (2021)

The variable clinical severity of mucous membrane pemphigoid (MMP) often leads to diagnostic and therapeutic delays.To describe the characteristics of a large cohort of patients with MMP.A retrospective review of clinical and diagnostic characteristics as well as treatment responses in 145 patients with MMP.Monosite involvement was seen in 41.4% and multisite involvement in 58.6% of the patients. The oral mucosa was affected in 86.9% of the patients, followed by the ocular mucosa (30.3%), skin (26.2%), genital mucosa (25.5%), nasal mucosa (23.4%), and pharyngeal and/or laryngeal mucosa (17.2%). Ocular disease developed during the disease course in 41.7% of patients with initially other mucosal site involvement. The malignancy rate was significantly higher in patients with autoantibodies against laminin-332 than in patients with MMP without laminin-332 autoantibodies (35.3% vs 10.9%, respectively; P = .007). Systemic immunosuppressive or immunomodulatory therapy was administered to 77.1% of the patients, mainly to patients with multisite (P < .001), ocular (P < .001), and pharyngeal and laryngeal involvement (P = .002). The remaining patients (22.9%) received topical therapy. Adverse events were frequently reported.Retrospective design.Patients with MMP present with a heterogeneous clinical presentation, and new symptoms may develop during the disease course. Cancer screening should be considered for patients with MMP and, in particular, for those with autoantibodies against laminin-332.
Subgroup Analysis: Efficacy and Safety of Panobinostat in Combination with SC Bortezomib and Oral Dexamethasone in Multiple Myeloma Patients with Lenalidomide-Refractory Disease
Authors: Joshua Richter, Jacob P. Laubach, Steve Stricker, Fredrik H. Schjesvold, David Cohan, Anna Sureda, Ewa Lech-Marańda, Meral Beksac, Vania Hungria, Meletios A. Dimopoulos, Ajai Chari, Paul G. Richardson, Philippe Moreau
Journal: Blood (2021)
HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001–18: an observational community cohort study
Authors: John S Santelli, Ivy S Chen, Dorean Nabukalu, Tom Lutalo, Esther J Spindler, Larry W Chang, Mary Kate Grabowski, Stephanie A Grilo, Philip Kreniske, Ying Wei, Fred Nalugoda, Susie Hoffman, Mahlet Maru, Sofia Chu, Fred M Ssewamala, William Byansi, Joseph Kagaayi, Maria J Wawer, Ronald H Gray, David Serwadda, Fred Makumbi
Journal: The Lancet HIV (2021)
Diagnosis and Management of Acute Appendicitis in Adults
Authors: Dimitrios Moris, Erik Karl Paulson, Theodore N. Pappas
Journal: JAMA (2021)

Acute appendicitis is the most common abdominal surgical emergency in the world, with an annual incidence of 96.5 to 100 cases per 100 000 adults.The clinical diagnosis of acute appendicitis is based on history and physical, laboratory evaluation, and imaging. Classic symptoms of appendicitis include vague periumbilical pain, anorexia/nausea/intermittent vomiting, migration of pain to the right lower quadrant, and low-grade fever. The diagnosis of acute appendicitis is made in approximately 90% of patients presenting with these symptoms. Laparoscopic appendectomy remains the most common treatment. However, increasing evidence suggests that broad-spectrum antibiotics, such as piperacillin-tazobactam monotherapy or combination therapy with either cephalosporins or fluroquinolones with metronidazole, successfully treats uncomplicated acute appendicitis in approximately 70% of patients. Specific imaging findings on computed tomography (CT), such as appendiceal dilatation (appendiceal diameter ≥7 mm), or presence of appendicoliths, defined as the conglomeration of feces in the appendiceal lumen, identify patients for whom an antibiotics-first management strategy is more likely to fail. CT findings of appendicolith, mass effect, and a dilated appendix greater than 13 mm are associated with higher risk of treatment failure (≈40%) of an antibiotics-first approach. Therefore, surgical management should be recommended in patients with CT findings of appendicolith, mass effect, or a dilated appendix who are fit for surgery, defined as having relatively low risk of adverse outcomes or postoperative mortality and morbidity. In patients without high-risk CT findings, either appendectomy or antibiotics can be considered as first-line therapy. In unfit patients without these high-risk CT findings, the antibiotics-first approach is recommended, and surgery may be considered if antibiotic treatment fails. In unfit patients with high-risk CT findings, perioperative risk assessment as well as patient preferences should be considered.Acute appendicitis affects 96.5 to 100 people per 100 000 adults per year worldwide. Appendectomy remains first-line therapy for acute appendicitis, but treatment with antibiotics rather than surgery is appropriate in selected patients with uncomplicated appendicitis.
Long-Term Air Pollution Exposure and COVID-19 Mortality: A Patient-Level Analysis from New York City
Authors: Anne Bozack, Stanley Pierre, Nicholas DeFelice, Elena Colicino, Darby Jack, Steven N. Chillrud, Andrew Rundle, Alfred Astua, James W. Quinn, Laura McGuinn, Qiang Yang, Keely Johnson, Joseph Masci, Laureen Lukban, Duncan Maru, Alison G. Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Risk factors for coronavirus disease (COVID-19) mortality may include environmental exposures such as air pollution. Objectives: To determine whether, among adults hospitalized with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), long-term air pollution exposure is associated with the risk of mortality, ICU admission, or intubation. Methods: We performed a retrospective analysis of SARS-CoV-2 PCR–positive patients admitted to seven New York City hospitals from March 8, 2020, to August 30, 2020. The primary outcome was mortality; secondary outcomes were ICU admission and intubation. We estimated the annual average fine particulate matter (particulate matter ⩽2.5 μm in aerodynamic diameter [PM2.5]), nitrogen dioxide (NO2), and black carbon (BC) concentrations at patients’ residential address. We employed double robust Poisson regression to analyze associations between the annual average PM2.5, NO2, and BC exposure level and COVID-19 outcomes, adjusting for age, sex, race or ethnicity, hospital, insurance, and the time from the onset of the pandemic. Results: Among the 6,542 patients, 41% were female and the median age was 65 (interquartile range, 53–77) years. Over 50% self-identified as a person of color (n = 1,687 [26%] Hispanic patients; n = 1,659 [25%] Black patients). Air pollution exposure levels were generally low. Overall, 31% (n = 2,044) of the cohort died, 19% (n = 1,237) were admitted to the ICU, and 16% (n = 1,051) were intubated. In multivariable models, a higher level of long-term exposure to PM2.5 was associated with an increased risk of mortality (risk ratio, 1.11 [95% confidence interval, 1.02–1.21] per 1-μg/m3 increase in PM2.5) and ICU admission (risk ratio, 1.13 [95% confidence interval, 1.00–1.28] per 1-μg/m3 increase in PM2.5). In multivariable models, neither NO2 nor BC exposure was associated with COVID-19 mortality, ICU admission, or intubation. Conclusions: Among patients hospitalized with COVID-19, a higher long-term PM2.5 exposure level was associated with an increased risk of mortality and ICU admission.
Superior Survival Outcome of Blinatumomab Compared to Mitoxantrone-Etoposide-Cytarabine Salvage for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: A Propensity Score-Matched Cohort Analysis
Authors: Jae-Ho Yoon, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Seok Lee
Journal: Blood (2021)