tbuckley/cabot-search huggingface dataset:
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Authors: David R. Spigel, Corinne Faivre-Finn, Jhanelle E. Gray, David Vicente, David Planchard, Luis Paz-Ares, Johan F. Vansteenkiste, Marina C. Garassino, Rina Hui, Xavier Quantin, Andreas Rimner, Yi-Long Wu, Mustafa Özgüroğlu, Ki H. Lee, Terufumi Kato, Maike de Wit, Takayasu Kurata, Martin Reck, Byoung C. Cho, Suresh Senan, Jarushka Naidoo, Helen Mann, Michael Newton, Piruntha Thiyagarajah, Scott J. Antonia
Journal: Journal of Clinical Oncology (2022)

The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method.Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS.These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.
Abstract P135: Adherence To Direct Oral Anticoagulants Across Chronic Kidney Disease Status
Authors: Yunwen Xu, Alex R Chang, Lesley Inker, Morgan Grams, Jung-im Shin
Journal: Circulation (2022)

Background: Adherence to anticoagulants is critical for effective stroke prevention for patients with atrial fibrillation (AF). Whether adherence to direct oral anticoagulants (DOACs) differs by chronic kidney disease (CKD) status remains uncertain. Methods: Using data from the Geisinger, we identified patients with AF initiating a DOAC between 2010-2019 and had at least one-year engagement prior and 3-month after initiation. To assess medication adherence, we compared proportion of days covered (PDC) by DOAC at 3, 6, 9, 12, and 18-month between patients with and without CKD, defined as estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m 2 . Poor adherence was defined as PDC &lt;0.8, indicating that a patient used the drug &lt;80% of the time. Results: Among the 4082 patients who initiated dabigatran (n=574), rivaroxaban (n=1502), or apixaban (n=2006), the mean (SD) age was 72 (12) years, 1083 (44%) were female, and the average eGFR was 73 (21) mL/min/1.73 m 2 . Overall, patients with CKD had lower adherence to DOAC compared to those without CKD (mean PDC: 0.89 vs. 0.91 at 3-month [P=0.03]; 0.87 vs. 0.89 at 6-month [P=0.04]; 0.84 vs. 0.87 at 9-month [P=0.02]; 0.83 vs. 0.86 at 12-month [P=0.05]; and 0.80 vs. 0.83 at 18-month [P=0.04]). For individual DOAC, only adherence to rivaroxaban was significantly lower in patients with CKD compared to those without CKD ( Figure ). Poor adherence to rivaroxaban was more common in CKD, particularly in the long-term (31% vs. 24% at 18-month [P=0.04]). Adherence to apixaban was highest and did not differ by CKD (CKD vs. non-CKD, mean PDC: 0.88 vs. 0.88 at 6-month; 0.85 vs. 0.85 at 12-month; and 0.81 vs. 0.83 at 18-month). Adherence to dabigatran was lowest and did not differ by CKD (CKD vs. non-CKD, mean PDC: 0.83 vs. 0.83 at 6-month; 0.76 vs. 0.78 at 12-month; and 0.73 vs. 0.74 at 18-month). Conclusion: Medication adherence was highest in apixaban users, followed by rivaroxaban and dabigatran users. Patients with CKD had lower adherence to rivaroxaban compared to those without CKD.
Abstract 010: Longitudinal Impact Of Glucose Homeostasis On Cardiac Structure And Function: Results From The Echocardiographic Study Of Latinos- 2 (echo-sol-2)
Authors: Patricia Chavez, Ayana K April-Sanders, Un Jung Lee, Jianwen Cai, Sonia Ponce, Matthew A Allison, Gregory A Talavera, Mayank M Kansal, Martha L Daviglus, Robert Ostfeld, Neil Schneiderman, Daniela Sotres-Alvarez, Leonor Corsino, Carlos Rodriguez
Journal: Circulation (2022)

Introduction: We assessed whether a longitudinal association between change in glucose homeostasis and change in cardiac structure and function was present. Methods: Data from ECHO-SOL baseline and visit 2 exams were used including 1643 Hispanic/Latino participants aged 45-74 years with serial echocardiograms obtained on average 4.3 (2.8-6.7) years apart. Glucose hoemostasis was evaluated through fasting plasma glucose levels (FGP), 2 hour oral glucose tolerance test (OGTT) and hemoglobin A1C (A1C) . Glucose homeostasis was categorized as: normal glucose tolerance (NGT) (FPG&lt;100 mg/dL, 2hr OGTT &lt;140 mg/dL, or A1C &lt;5.7%), prediabetes (PDM) (FPG 100–125 mg/dL, or 2h OGTT 140–199 mg/dL, or A1C 5.7–6.4%); among those with self-report of diabetes or currently taking diabetes medicine: controlled diabetes (CDM) (A1C&lt;7), and uncontrolled diabetes (UDM) (A1C&gt;7). Linear regression models were used to examine associations between change in glucose homeostasis [worsening (NGT to PDM, NGT to DM, PDM to DM, CDM to UDM) vs unchanged] with changes in left ventricular mass (LVM), relative wall thickness (RWT), ejection fraction (EF), global longitudinal strain (GLS) and E’ velocity. All analyses were weighted to account for the complex survey design. Results: At baseline (mean age 56.4 years ±0.35; 45.4% male), glucose regulation was as follows: NGT (29.1%), PDM (51.8%), CDM (9.2%) and UDM (9.9%). At visit 2, glucose downregulation was as follows: NGT to PDM (55.9%), NGT to DM (13.4%), PDM to DM (27.4%), CDM to UCDM (33.5%). Among those with worsening glucose homeostasis the average age was 55.2 ±0.50 years, 45.7% were male, FPG was 99.4±0.90mg/dL . Change from NGT to PDM compared to remaining at NGT was associated with increase LVM (b=4.0 ±0.9, p&lt;0.001), worsening in GLS (b=0.6 ±0.1, p&lt;0.001) and decrease in E’ velocity (b=-1.1 ±0.1, p&lt;0.001). Neither change from NGT to DM nor from PDM to DM was associated with significant changes in cardiac structure and function. Change from CDM to UDM was associated with increase in RWT (b=0.1 ±0.0, p&lt;0.05), compared to those with unchanged CDM. Worsening glucose homeostasis from any group was not associated with changes in EF. Conclusions: Early stages of worsening glucose homeostasis were associated with cardiac structural and functional changes. Identification of those at risk of developing prediabetes may provide opportunities to prevent future cardiac dysfunction.
Seeing the Invisible: The Value of Bone Scan to Distinguish Chondroblastic Osteosarcoma From Prosthesis Loosening.
Authors: Tzyy-Ling Chuang, Yu-Ruei Chen, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2022)

A 76-year-old woman with uterine cervical cancer 20 years ago received right total hip replacement 3 months ago for right hip avascular necrosis without specific intraoperative finding. She reported persistent right hip pain after falling from bed. Pelvic x-ray showed right pubic ramus fracture. To evaluate prosthesis loosening, 99mTc-MDP 3-phase bone scan was arranged, showing diffusely and heterogeneously increased vascularity and tracer perfusion over the right hip, with intensely and heterogeneously increased metabolism in the right iliac bone and hip. SPECT/CT showed nearby swelling of calcified muscles. After debridement and synovectomy, the pathologic report showed chondroblastic osteosarcoma.
Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination
Authors: Terry O Harville, John M Arthur
Journal: New England Journal of Medicine (2022)

group (23 patients, 11.2%) was higher than that in the nosurgery group (12 patients, 5.8%) at 24 months, representing an excess of 11 patients.If only one of the patients had died within this time frame, the results would no longer be signifi cant, according to an unstratified logrank test. 4 This assumption is conservative, since approxi mately 1 of 5 patients in the surgery group died within 24 months.The doubling of the increase in early censoring may be due to postoperative complications that were not accounted for in pa tients who were lost to followup.Some of the measured effect could be a product of the inher ent Kaplan-Meier limitations when excessive censoring exists. 3 Further investigation is war ranted to elucidate the implications and underly ing reasons for excessive censoring in the De scriptive Evaluation of Preoperative Selection Criteria for Operability in Recurrent Ovarian Cancer (DESKTOP) III trial.
Abstract P057: Proteomic Signature Of Healthy Dietary Patterns And Risk Of Cardiovascular Disease In The Framingham Heart Study
Authors: Maura E Walker, Vanessa Xanthakis, Honghuang Lin, Paul Jacques, Vasan S Ramachandran
Journal: Circulation (2022)

Background: Identifying circulating proteins associated with healthy dietary patterns may offer novel insights into the key biological processes underlying diet-related chronic disease. As a first step toward achieving this goal, we examined the relations between a proteomic score of healthy dietary patterns and the risk of cardiovascular disease (CVD). Methods: We evaluated up to 1713 Framingham Offspring Study participants (1991-1995, mean age 54yr, 55% women) who had plasma proteins assayed using the SomaLogic platform and diet assessed using a validated food frequency questionnaire. We regressed three healthy dietary pattern indices (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension [DASH], and Mediterranean-style diet) on 103 diet-related proteins using elastic net regression (separate model for each diet index) with a 10-fold cross-validation (CV). Protein selection was based on the minimum mean CV error. A proteomic score was created by summing (concentration*β coefficient) of selected proteins, and validated in 862 Framingham Third Generation Cohort participants (2008-2011, mean age 46yr, 56% women). We used multivariable Cox proportional hazard models to relate the proteomic score and dietary pattern indices (separate models) to CVD in participants free of CVD (n=2459). All models adjusted for age, sex, smoking, and lipid medication use. Additional models adjusted for 1) both the proteomic score and dietary pattern indices and 2) body mass index, total cholesterol to high-density lipoprotein cholesterol ratio, triglycerides, diabetes mellitus, and hypertension. Results: Across three dietary patterns, 11 proteins characterized the proteomic score. Partial correlations of the proteomic score with the healthy dietary patterns ranged from r=0.33-0.36 (adjusted for age, sex, and total energy) in the validation sample, with the strongest correlation for the DASH index. Over a mean follow-up of 20 years, 510 participants developed CVD. Adjusting for age, sex, smoking, and lipid medication, a 1-SD unit increase in the proteomic score was associated with a 22% lower risk of CVD (hazard ratio [95% CI] 0.78 [0.72, 0.84]) and a 1-SD unit increase in the DASH index was associated with a 15% lower risk of CVD (hazard ratio 0.85 [0.77, 0.93). In mutually-adjusted models, relations of the proteomic score with CVD (0.80 [0.73, 0.87]), and of the DASH index with CVD were maintained (0.89 [0.82, 0.97]). Upon further adjustment for metabolic risk factors, relations of the proteomic score and CVD were attenuated (0.96 [0.87, 1.05]), but relations of the DASH index with CVD were unchanged (0.89 [0.80, 0.98]). Conclusion: We characterized a distinct proteomic score of healthy dietary patterns in a community-based cohort of adults. A healthy diet proteomic score may represent variation in the proteome that influences CVD risk.
ICOS Is Widely Expressed in Cutaneous T-Cell Lymphoma and Its Targeting Promotes Potent Killing of Malignant Cells
Authors: Florent Amatore, Nicolas Ortonne, Marc Lopez, Mathilde Barré, Florence Orlanducci, Remy Castellano, Saskia Ingen-Housz-Oro, Amandine De Croos, Laurent Gorvel, Armelle Goubard, Reda Bouabdallah, Jean Marc Schiano De Colella, Jean-Jacques Grob, Philippe Gaulard, Martine Bagot, Armand Bensussan, Emmanuel Delaporte, Daniel Olive
Journal: Blood (2021)
Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data
Authors: Chengyi Zheng, Jonathan Duffy, In-Lu Amy Liu, Lina S. Sy, Wansu Chen, Lei Qian, Ronald A. Navarro, Denison S. Ryan, Sunhea S. Kim, Cheryl Mercado, Steven J. Jacobsen
Journal: Annals of Internal Medicine (2022)

Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited.To estimate the risk for shoulder conditions after vaccination and assess possible risk factors.Retrospective cohort study.Kaiser Permanente Southern California, a large integrated health care organization.Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017.A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared.Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons.Generalizability to other health care settings, use of administrative data, and residual confounding.These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks.Centers for Disease Control and Prevention.
Understanding Drug Sensitivity and Tackling Resistance in Cancer
Authors: Jeffrey W. Tyner, Franziska Haderk, Anbarasu Kumaraswamy, Linda B. Baughn, Brian Van Ness, Song Liu, Himangi Marathe, Joshi J. Alumkal, Trever G. Bivona, Keith Syson Chan, Brian J. Druker, Alan D. Hutson, Peter S. Nelson, Charles L. Sawyers, Christopher D. Willey
Journal: Cancer Research (2022)

Abstract Decades of research into the molecular mechanisms of cancer and the development of novel therapeutics have yielded a number of remarkable successes. However, our ability to broadly assign effective, rationally targeted therapies in a personalized manner remains elusive for many patients, and drug resistance persists as a major problem. This is in part due to the well-documented heterogeneity of cancer, including the diversity of tumor cell lineages and cell states, the spectrum of somatic mutations, the complexity of microenvironments, and immune-suppressive features and immune repertoires, which collectively require numerous different therapeutic approaches. Here, we describe a framework to understand the types and biological causes of resistance, providing translational opportunities to tackle drug resistance by rational therapeutic strategies.
Cover Image, Volume 42, Issue 4
Authors: Xiao Zhang, Yunhua Xu, Lifang Ma, Keke Yu, Yongjie Niu, Xin Xu, Yi Shi, Susu Guo, Xiangfei Xue, Yikun Wang, Shiyu Qiu, Jiangtao Cui, Hong Wang, Xiaoting Tian, Yayou Miao, Fanyu Meng, Yongxia Qiao, Yongchun Yu, Jiayi Wang
Journal: Cancer Communications (2022)

The cover image is based on the Original Article Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma by Jiayi Wang et al., https://doi.org/10.1002/cac2.12275.
18F-PSMA-1007 Uptake in Paget Disease of the Bone: An “Iron Man” Sign
Authors: Mahamoud Alfeeli, Fahad Marafi, Abdulredha Esmail, Wael M.A. Fathallah, Sharjeel Usmani
Journal: Clinical Nuclear Medicine (2021)

18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the benign pathological conditions. We report a case of 81-year-old man with a known case of prostate cancer who underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows intense tracer uptake in the frontal bone appearing like an "Iron Man" sign. Corresponding noncontrast CT images, pagetoid changes with thickened cortex, mixed lytic/sclerotic mottled pattern. It is important to recognize 18F-PSMA expression in the benign nonprostatic pathologies to avoid false interpretation.
Neutrophil extracellular traps in cardiac hypertrophy: a KLF2 perspective
Authors: Dario F. Riascos-Bernal, Nicholas E.S. Sibinga
Journal: Journal of Clinical Investigation (2022)

About 6 million adults in the United States have heart failure, and the mortality five years after diagnosis remains high at approximately 50%. Incomplete understanding of disease pathogenesis limits therapeutics, especially in the case of heart failure with preserved ejection fraction, a condition commonly associated with cardiac hypertrophy. Neutrophils, the most abundant leukocyte in blood, have functions beyond antimicrobial activity and participate in both sterile inflammation and disease; however, their role in nonischemic cardiac hypertrophy and heart failure is underexplored. In this issue of the JCI, Tang et al. show that neutrophil extracellular trap (NET) formation contributes to cardiac hypertrophy and dysfunction in a mouse model of angiotensin II-induced cardiomyopathy, and that Krüppel-like factor 2 (KLF2) functions in neutrophils to oppose this process. Whether a neutrophil-centered strategy may benefit patients with cardiac hypertrophy and failure deserves further investigation.
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization
Authors: Guy Witberg, Noam Barda, Sara Hoss, Ilan Richter, Maya Wiessman, Yaron Aviv, Tzlil Grinberg, Oren Auster, Noa Dagan, Ran D. Balicer, Ran Kornowski
Journal: New England Journal of Medicine (2021)

BackgroundReports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.MethodsWe searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer–BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan–Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.ResultsAmong more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.ConclusionsAmong patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)
A Urinary Drug-Disposing Approach as an Alternative to Intravesical Chemotherapy for Treating Nonmuscle Invasive Bladder Cancer
Authors: Vanessa Bellat, Adam O. Michel, Charlene Thomas, Tracy Stokol, Benjamin B. Choi, Benedict Law
Journal: Cancer Research (2022)

Abstract The standard treatment of nonmuscle invasive bladder cancer (NMIBC) is transurethral resection of the tumors, followed by intravesical therapy (IT), which comprises a direct instillation of a solution of Bacillus Calmette-Guérin vaccine or chemotherapy into the bladder. However, the recurrence rate in this disease remains unacceptably high. IT is a local treatment that fails to reach tumors developed in the upper urinary tract (ureter and renal pelvis). The catheterization procedure required for IT is invasive, painful, and poses an increased infection risk, resulting in poor patient quality of life and compliance. There is an unmet need for a potent, comprehensive, and noninvasive option. Without chemical modifications, peptides are rapidly removed by renal clearance. This “shortcoming” can be advantageous when used as a drug carrier for directing therapy to NMIBC. Here we develop a urinary drug-disposing (UDD) approach to improve NMIBC treatment. A 12-amino acid bio-inert peptide (Bdd) that can be exclusively eliminated via renal filtration was generated for delivering the microtubule inhibitor DM1 to NMIBC with minimal nonspecific accumulation in other organs. The UDD approach prolonged survival of mice bearing human bladder tumors. Unlike IT, the treatment was given noninvasively (intravenously). Furthermore, it was more effective at suppressing tumor growth than clinically used IT (mitomycin) and safer than free DM1. The application of this UDD approach to treat kidney tumors and deliver other drugs such as doxorubicin was also demonstrated. Overall, the rapid renal clearance of peptides can be exploited to direct cancer therapies to the urinary system. Significance: A noninvasive drug delivery approach that targets the urinary system overcomes the current barriers facing effective treatment of bladder cancer.