tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 in Childhood Cancer in 2020: A Disease of Disparities
Authors: Emily E. Johnston, Isaac Martinez, Elizabeth S. Davis, Caroline Caudill, Joshua Richman, Julienne Brackett, David S. Dickens, Alissa Kahn, Carla Schwalm, Archana Sharma, Pratik A. Patel, Smita Bhatia, Jennifer M. Levine, Julie A. Wolfson
Journal: Journal of Clinical Oncology (2021)

The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2.This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy.Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6% v 29.7%, P < .01), publicly insured (59.3% v 33.5%, P < .01), and patients with hematologic malignancies (65.8% v 38.3%, P < .01) in our cohort. The majority (64.1%) were symptomatic; 31.2% were hospitalized, 10.9% required respiratory support, 9.2% were admitted to the ICU, and 1.6% died because of SARS-CoV-2. Cancer therapy was modified in 44.9%. Hispanic ethnicity was associated with changes in cancer-directed therapy (adjusted risk ratio [aRR] = 1.3; 95% CI, 1.1 to 1.6]). Presence of comorbidities was associated with hospitalization (aRR = 1.3; 95% CI, 1.1 to 1.6) and ICU admission (aRR = 2.3; 95% CI, 1.5 to 3.6). Hematologic malignancies were associated with hospitalization (aRR = 1.6; 95% CI, 1.3 to 2.1).These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.
Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy
Authors: Fernanda G. Herrera, Catherine Ronet, Maria Ochoa de Olza, David Barras, Isaac Crespo, Massimo Andreatta, Jesus Corria-Osorio, Aodrenn Spill, Fabrizio Benedetti, Raphael Genolet, Angela Orcurto, Martina Imbimbo, Eleonora Ghisoni, Blanca Navarro Rodrigo, Dominik R. Berthold, Apostolos Sarivalasis, Khalil Zaman, Rafael Duran, Clarisse Dromain, John Prior, Niklaus Schaefer, Jean Bourhis, Georgia Dimopoulou, Zoi Tsourti, Marius Messemaker, Thomas Smith, Sarah E. Warren, Periklis Foukas, Sylvie Rusakiewicz, Mikaël J. Pittet, Stefan Zimmermann, Christine Sempoux, Urania Dafni, Alexandre Harari, Lana E. Kandalaft, Santiago J. Carmona, Denarda Dangaj Laniti, Melita Irving, George Coukos
Journal: Cancer Discovery (2021)

Abstract Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell–infiltrated tumors. Significance: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors. This article is highlighted in the In This Issue feature, p. 1
Primary Solitary Tuberculosis in the Hepatic Round Ligament Detected by 68Ga-FAPI PET/CT
Authors: Ying Deng, Junhao Wu, Chuanqi Xu, Wei Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract A 45-year-old woman recently complained of abdominal pain, poor appetite, and weight loss. Her serum ferritin, CA199, and CA242 levels were elevated. 68 Ga-FAPI PET/CT revealed a subcapsular mass in the liver, which showed a significant FAPI uptake without other abnormal activity. Postoperative pathological examination confirmed tuberculosis in the hepatic round ligament.
Abstract 009: Differential Effect Of An Intensive Lifestyle Intervention On Risk For Cardiovascular Events According To Baseline Level Of Glycated Hemoglobin
Authors: Michael P Bancks, Joseph Rigdon, Ashok Balasubramanyam, Scott Pilla, Hsin-Chieh Yeh, Karen C Johnson, Lynne E Wagenknecht, Mark A Espeland
Journal: Circulation (2022)

Introduction: A lack of effective interventions remains a major clinical gap in cardiovascular disease (CVD) prevention for individuals with type 2 diabetes (T2D) and high glycated hemoglobin (HbA1c). Our objective was to determine whether the effect of an intensive lifestyle intervention (ILI) on CVD prevention differed by baseline HbA1c among Action for Health in Diabetes (Look AHEAD) trial participants. Hypothesis: ILI will be associated with differential risk for CVD by HbA1c. Methods: Look AHEAD randomized 5145 adults, aged 45-76 years, with T2D and overweight/obesity, to ILI or a control of diabetes support and education (DSE) for a median of 9.6 years. ILI focused on weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial’s pre-specified primary CVD outcome. We assessed for additive (Poisson regression) and multiplicative (Cox proportional hazards) heterogeneity of intervention effects on CVD risk by HbA1c adjusting for stratified randomization and using intention to treat analysis. Results: Baseline HbA1c ranged from 4.4% to 14.5% (mean 7.3, SD 1.2). We observed additive and multiplicative heterogeneity of effects (all p&lt;0.001) between ILI and HbA1c on CVD risk (Figure). Compared to DSE, ILI was associated with lower risk for CVD for HbA1c quintiles 1 and 2. The “ILI-CVD” association changed direction at HbA1c=7.7%; ILI was associated with higher risk of CVD than DSE within HbA1c quintile 5 (and when continuous, HbA1c ≥8.7%). Conclusion: Among adults with T2D and overweight/obesity, the effect of a lifestyle intervention on CVD risk differed by HbA1c. There is a critical need to identify effective CVD prevention strategies for individuals with T2D and high HbA1c.
Decoding grasp and speech signals from the cortical grasp circuit in a tetraplegic human
Authors: Sarah K. Wandelt, Spencer Kellis, David A. Bjånes, Kelsie Pejsa, Brian Lee, Charles Liu, Richard A. Andersen
Journal: Neuron (2022)

The cortical grasp network encodes planning and execution of grasps and processes spoken and written aspects of language. High-level cortical areas within this network are attractive implant sites for brain-machine interfaces (BMIs). While a tetraplegic patient performed grasp motor imagery and vocalized speech, neural activity was recorded from the supramarginal gyrus (SMG), ventral premotor cortex (PMv), and somatosensory cortex (S1). In SMG and PMv, five imagined grasps were well represented by firing rates of neuronal populations during visual cue presentation. During motor imagery, these grasps were significantly decodable from all brain areas. During speech production, SMG encoded both spoken grasp types and the names of five colors. Whereas PMv neurons significantly modulated their activity during grasping, SMG's neural population broadly encoded features of both motor imagery and speech. Together, these results indicate that brain signals from high-level areas of the human cortex could be used for grasping and speech BMI applications.
16P Camrelizumab monotherapy or plus apatinib for PD-L1-positive advanced pulmonary sarcomatoid carcinoma: A single-arm, open-label, multicenter, phase II study
Authors: M. Zhao, X. Liu, C. Yuan, W. Zheng, D. Zhang, Q. Long, J. Li, T. Han, L. Xu, H. Li, X. Li, S. Shi
Journal: Annals of Oncology (2022)
Abstract P131: Cerebral Venous Sinus Thrombosis Risk Factors, Treatments, And Sequelae: 2011-2019
Authors: Rob F Walker, Pamela L Lutsey, Neil A Zakai, Richard F Maclehose, Diego Adrianzen-Herrera, Alvaro Alonso, Terrence J Adam
Journal: Circulation (2022)

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare but potentially debilitating thrombosis affecting 3-4 cases per million adults in the United States. Risk factors are thought similar to venous thrombosis, but there is little epidemiologic data corroborating this assertion. Concern about a possible association between the Janssen (Johnson and Johnson) and Oxford-AztraZenaca COVID-19 vaccines and cases of CVST resulted in increased global attention to this condition. Thus, large epidemiological assessment of the risk factors, treatment and outcomes of CVST are needed. Objective: Estimate the distributions of risk factors antecedent to CVST diagnosis, report CVST treatments in clinical practice, and potential sequelae of CVST in a large retrospective cohort of adults with CVST in the United States. Methods: MarketScan Commercial and Medicare Supplemental administrative databases were employed to assess CVST diagnosed between 2011 and 2019 in the U.S. Validated International Classification of Disease (ICD) codes and receipt of an outpatient anticoagulant (either oral or subcutaneous anticoagulant) prescription within 30 days of the ICD code identified incident CVST. Antecedent clinical characteristics, treatments, and sequelae of CVST were identified using inpatient, outpatient, and prescription data. For outcomes, proportions and incidence with 95% confidence intervals (CIs) were calculated, stratified by sex. Results: We identified 1,869 CVST patients. Of these 1,314 (70%) were female, with 200 (10%) events identified as a pregnancy-related CVST. The average age was 41 years for females and 48 years for men. Among women, 24.7% were on hormonal therapy (oral contraceptive, estrogen, and progestin) prior to diagnosis. Men had a higher prevalence of comorbidities, such as diabetes (15% men vs. 9% women) and cancer (19% men vs. 10% women). Oral anticoagulant (OAC) use was the most common treatment for CVST in both men (88%) and women (85%) and did not vary by sex. Use of procedures to treat CVST, optic nerve fenestration and catheter directed thrombolysis, were 0.5% and 4.1%, respectively. The most common sequela after CVST was incidence of intracranial hypertension (Incidence: 4.2 per 100 person-years; 95% CI: 3.3, 5.1) and palliedema was rare. Conclusions: Overall, a majority of CVST patients were women of reproductive age. Our findings suggest a potential association with both endogenous (pregnancy) and exogenous (oral contraceptives, HRT) hormones which needs further study. In our sample, CVST was managed with oral anticoagulants, regardless of sex, and intracranial hypertension was elevated following CVST. This large claims-based analysis is a descriptive insight into the risk factors and management of CVST, a rare and debilitating condition.
Ending tuberculosis in China: health system challenges
Authors: Qian Long, Lei Guo, Weixi Jiang, Shitong Huan, Shenglan Tang
Journal: The Lancet Public Health (2021)

China has made remarkable progress in reducing tuberculosis cases and deaths during the past three decades; however, it is still far from achieving the targets set out in the WHO End TB Strategy. Since the 2000s, China has tried to transform its vertical tuberculosis control programme led by the Chinese Center for Disease Control and Prevention (CDC) into an integrated system under the collaboration of CDC, tuberculosis-designated hospitals, and primary health centres. Such a transition has faced many challenges. Profit-driven practices in hospitals designated to tuberculosis and an absence of adequate tuberculosis-related training for health professionals are partially jeopardising the quality of tuberculosis care. In addition, primary health-care providers are not incentivised to make referrals and manage cases effectively. The CDC does not have the administrative power to influence hospital practices or deploy resources to support community-based tuberculosis control activities. Furthermore, an absence of policy coherence and effective coordination causes challenges for quality tuberculosis care that is affordable and accessible. Improving policy dialogues and multi-level coordination within the government is fundamental to successfully ending tuberculosis in China and other countries facing similar challenges.
Temporal Trends in the Remaining Lifetime Risk of Cardiovascular Disease Among Middle-Aged Adults Across 6 Decades: The Framingham Study
Authors: Ramachandran S. Vasan, Danielle M. Enserro, Vanessa Xanthakis, Alexa S. Beiser, Sudha Seshadri
Journal: Circulation (2022)

Background: The remaining lifetime risk (RLR) is the probability of developing an outcome over the remainder of one’s lifespan at any given age. The RLR for atherosclerotic cardiovascular disease (ASCVD) in three 20-year periods were assessed using data from a single community-based cohort study of predominantly White participants. Methods: Longitudinal data from the Framingham study in 3 epochs (epoch 1, 1960–1979; epoch 2, 1980–1999; epoch 3, 2000–2018) were evaluated. The RLR of a first ASCVD event (myocardial infarction, coronary heart disease death, or stroke) from 45 years of age (adjusting for competing risk of death) in the 3 epochs were compared overall, and according to the following strata: sex, body mass index, blood pressure and cholesterol categories, diabetes, smoking, and Framingham risk score groups. Results: There were 317 849 person-years of observations during the 3 epochs (56% women; 94% White) and 4855 deaths occurred. Life expectancy rose by 10.1 years (men) to 11.9 years (women) across the 3 epochs. There were 1085 ASCVD events over the course of 91 330 person-years in epoch 1, 1330 ASCVD events over the course of 107 450 person-years in epoch 2, and 775 ASCVD events over the course of 119 069 person-years in epoch 3. The mean age at onset of first ASCVD event was greater in the third epoch by 8.1 years (men) to 10.3 years (women) compared with the first epoch. The RLR of ASCVD from 45 years of age declined from 43.7% in epoch 1 to 28.1% in epoch 3 ( P &lt;0.0001), a finding that was consistent in both sexes (RLR [epoch 1 versus epoch 3], 36.3% versus 26.5% [women]; 52.5% versus 30.1% [men]; P &lt;0.001 for both). The lower RLR of ASCVD in the last 2 epochs was observed consistently across body mass index, blood pressure, cholesterol, diabetes, smoking, and Framingham risk score strata ( P &lt;0.001 for all). The RLR of coronary heart disease events and stroke declined in both sexes ( P &lt;0.001). Conclusions: Over the past 6 decades, mean life expectancy increased and the RLR of ASCVD decreased in the community-based, predominantly White Framingham study. The residual burden of ASCVD underscores the importance of continued and effective primary prevention efforts with better screening for risk factors and their effective treatment.
Training can’t always lead to Olympic macrophages
Authors: Erwan Pernet, Renaud Prevel, Maziar Divangahi
Journal: Journal of Clinical Investigation (2022)

Although the memory capacity of innate immune cells, termed trained immunity (TI), is a conserved evolutionary trait, the cellular and molecular mechanisms involved are incompletely understood. One fundamental question is whether the induction of TI generates a homogeneous or heterogeneous population of trained cells. In this issue of the JCI, Zhang, Moorlag, and colleagues tackle this question by combining an in vitro model system of TI with single-cell RNA sequencing. The induction of TI in human monocytes resulted in three populations with distinct transcriptomic profiles. Interestingly, the presence of lymphocytes in the microenvironment of monocytes substantially impacted TI. The authors also identified a similar population of monocytes in various human diseases or in individuals vaccinated with bacillus Calmette-Guérin. These insights warrant in-depth analysis of TI in responsive versus nonresponsive immune cells and suggest that modulating TI may provide a strategy for treating infections and inflammatory diseases.
The Liver–Immunity Nexus and Cancer Immunotherapy
Authors: James C. Lee, Michael D. Green, Laura A. Huppert, Christine Chow, Robert H. Pierce, Adil I. Daud
Journal: Clinical Cancer Research (2021)

The impact of liver metastases on immune checkpoint-inhibitor effectiveness in patients with solid-tumor malignancies has been the focus of several recent clinical and translational studies. We review the literature describing the immune functions of the liver and particularly the mechanistic observations in these studies. The initial clinical observation was that pembrolizumab appeared to be much less effective in melanoma and non-small cell lung cancer (NSCLC) patients with liver metastasis. Subsequently other clinical studies have extended and reported similar findings with programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors in many cancers. Two recent translational studies in animal models have dissected the mechanism of this systemic immune suppression. In both studies CD11b+ suppressive macrophages generated by liver metastasis in a two-site MC38 model appear to delete CD8+ T cells in a FasL-dependent manner. In addition, regulatory T-cell (Treg) activation was observed and contributed to the distal immunosuppression. Finally, we discuss some of the interventions reported to address liver immune suppression, such as radiation therapy, combination checkpoint blockade, and Treg depletion.
The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Authors: Julio Delgado, Irene Papadouli, Sinan B. Sarac, Alexandre Moreau, Doris Hovgaard, Christian Gisselbrecht, Harald Enzmann, Francesco Pignatti
Journal: HemaSphere (2021)

Tafasitamab is a humanized monoclonal antibody that binds to the CD19 antigen, which is expressed in tumor cells from patients with diffuse large B-cell lymphoma (DLBCL). On June 24, 2021, a positive opinion for a conditional marketing authorization was issued by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) for tafasitamab, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory DLBCL who are ineligible for autologous stem cell transplantation. Tafasitamab was evaluated in the phase 2 single-arm, multicenter, open-label L-MIND clinical trial. The primary endpoint of this trial was objective response rate (ORR). The best ORR, achieved at any time during the study, was 56.8% (95% confidence interval: 45.3%–67.8%), and the median duration of response was 34.6 months (95% confidence interval: 26.1–not reached). The most frequently reported adverse events by system organ class were infections and infestations (72.8%; grade ≥3: 29.6%), blood and lymphatic system disorders (65.4%; grade ≥3: 56.8%), gastrointestinal disorders (64.2%; grade ≥3: 2.5%), and general disorders and administration site conditions (58.0%; grade ≥3: 8.6%). The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the CHMP.
Abstract MP02: Association Of Socioeconomic Status With Stroke In Non-elderly Adults
Authors: Ryan T Nguyen, Safi U Khan, Javier Valero-Elizondo, Miguel Cainzos-Achirica, Khurram Nasir
Journal: Circulation (2022)

Background: Stroke is increasing among the non-elderly adults (&lt;65 years of age) in the United States (US). We investigated the combined effects of socioeconomic status (SES), race/ethnicity, and traditional risk factors on stroke in this population. Methods: Using the National Health Interview Survey (NHIS) database from 2012 to 2018, we examined the association of traditional risk factors (hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity), sociodemographic, cardiovascular risk factor (CRF) profile (CRF range: Optimal (0-1 cardiovascular risk factors) to Poor (≥ 4 cardiovascular risk factors)), family income (high to low based on income as percentage of poverty limit), and educational attainment (categorized as some college degree or higher vs high school (HS) degree/GED or less) with stroke in the young (18-44 years) and middle-aged (45-64 years) adults. Results: Among 168,862 non-elderly adults (55% in young adults) included in this study, the prevalence of stroke was 1.83% among the non-elderly which translates to roughly 3.1 million adults. Of these, 598 and 2,509 were young- and middle-aged adults, translating to 624,000 and 2.5 million US adults, respectively. Adults with low family income, lesser education, and who were black were more likely to have stroke. The majority of young adults without stroke had an optimal CRF profile (65%) with only 3.5% having a poor profile. In contrast, 17.7% of middle-aged adults had a poor CRF profile. Lower income status coupled with a poor CRF profile increased the odds of stroke in both young (adjusted [a]OR: 3.12 [2.12-4.59]) and middle-aged (aOR: 2.31 [1.97-2.72]) adults when compared to those with average or optimal CRF profiles. Conclusions: This national survey of non-elderly US adults showed that poor CRF profiles led to higher odds of stroke compared to optimal profiles. Additionally, low income and education, factors contributing to SES, and race/ethnicity contributed to worsening stroke odds.