tbuckley/cabot-search huggingface dataset:
Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial
Authors: Margarita Majem, Jonathan W. Goldman, Thomas John, Christian Grohe, Konstantin Laktionov, Sang-We Kim, Terufumi Kato, Huu Vinh Vu, Shun Lu, Shanqing Li, Kye Young Lee, Charuwan Akewanlop, Chong-Jen Yu, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Shinji Atagi, Lingmin Zeng, Dakshayini Kulkarni, Nenad Medic, Masahiro Tsuboi, Roy S. Herbst, Yi-Long Wu
Journal: Clinical Cancer Research (2022)

Abstract Purpose: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB–IIIA EGFR-mutated (EGFRm) non–small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. Patients and Methods: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB–IIIA; N = 682). Clinically meaningful changes were defined using the SF-36 manual. Results: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46–47) and maintained to Week 96, with no clinically meaningful differences between arms; difference in adjusted least squares (LS) mean [95% confidence intervals (CI), −1.18 (−2.02 to −0.34) and −1.34 (−2.40 to −0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS; HR, 1.17 (95% CI, 0.82–1.67) and HR, 0.98 (95% CI, 0.70–1.39), respectively. Conclusions: HRQoL was maintained with adjuvant osimertinib in patients with stage IB–IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204
Peptide Receptor Radionuclide Therapy by 177Lu-DOTATATE of a Secreting Cervical Paraganglioma
Authors: Agathe Deville, Iuliia Pinigina, Laure Al Mansour, Juliette Abeillon, Jeremie Tordo
Journal: Clinical Nuclear Medicine (2021)

Abstract A 59-year-old man with a parapharyngeal paraganglioma incidentally discovered on a cervical swelling was referred to our nuclear medicine department for a morpho-metabolic assessment. An 18 F-FDG PET/CT was initially performed and found an intense hypermetabolism of the lesion and a hypermetabolism of the periadrenal brown fat evoking catecholamine secretion. An additional 68 Ga-DOTATOC PET/CT was performed, showing an overexpression of the somatostatin receptors of this isolated paraganglioma. After multidisciplinary discussion, a peptide receptor radionuclide therapy with somatostatin analogs using 177 Lu-DOTATATE as a compassionate measure was carried out.
Rapid cloning of antigen-specific T-cell receptors by leveraging the cis activation of T cells
Authors: Eiji Kobayashi, Aishun Jin, Hiroshi Hamana, Kiyomi Shitaoka, Kazuto Tajiri, Seisuke Kusano, Shigeyuki Yokoyama, Tatsuhiko Ozawa, Tsutomu Obata, Atsushi Muraguchi, Hiroyuki Kishi
Journal: Nature Biomedical Engineering (2022)
Exposure to household air pollution from cooking fuel in Ugandan households and associated household factors: a retrospective analysis of demographic and health survey data
Authors: Derrick Bary Abila, Racheal Nalunkuma, Sulaiman Bugosera Wasukira, Provia Ainembabazi, Elizabeth Kiyingi Nakiyingi, Asia Mustafa, Yusuff Adebayo Adebisi, Don Eliseo Lucero-Prisno
Journal: The Lancet Global Health (2022)

Household air pollution is mostly caused by cooking fuel. We describe the trend in household air pollution (HAP) caused by several types of cooking fuel used in Ugandan households from 2001 to 2016 and explore the household factors associated with it.We did a retrospective analysis of data from four Ugandan demographic and health surveys (UDHS) that were conducted from 2000-01 to 2016, with the household as the unit of analysis. We included all households that were in the UDHS dataset. We included variables that described the households, the type of cooking fuel, and where the food was cooked. A household was considered to have exposure to HAP if they used cooking fuels such as coal; charcoal; wood; straw, shrubs, or grass; crops; or animal dung. Bivariate and multivariate logistic regression was used to determine the association between household characteristics and exposure to household air pollution (HAP) from the most recent UDHS of 2016. The DHS programme obtained relevant ethics approval within Uganda and informed consent was provided by the participants.In this study, 45 376 households were included and surveyed. In all the surveys, most households were in rural areas (from 74·3% to 85·1%) and had a male as a head of household (from 69·0% to 72·5%. Wood was the most used household cooking fuel (from 71·7% to 82·1%). Other cooking fuels used were charcoal (from 15·3% to 26·3%), kerosene (from 0·7% to 2·5%) and electricity (0·1% to 0·8%). Exposure to HAP remained high in all the surveys ranging from 96·7% to 99·8%. From the multivariate logistic regression analysis, households with a household head having attained either complete secondary education (adjusted odds ratio 0·13, 95% CI 0·03-0·58; p=0·008) or higher education (0·11, 0·03 - 0·48; p=0·003) were less likely to be exposed to HAP than households with a household head having no education.This study revealed that most households in Uganda have exposure to household air pollution caused by different types of cooking fuel used in the household. This underscores the need for innovations in cooking fuels such as clean energy stoves that are cost-effective and cause less exposure to household air pollution.None.
Abstract P082: Association Of Breast Arterial Calcification With Atrial Fibrillation Among Postmenopausal Women
Authors: Carlos Iribarren, Malini Chandra, Rishi V Parikh, Gabriela Sanchez, Danny L Sam, Farima F Azamian, Hyo-Min Cho, Huanjun Ding, Sabee Molloi, Alan S Go
Journal: Circulation (2022)

Coronary artery calcium (CAC) is independently associated with incident atrial fibrillation (AF). Breast arterial calcification (BAC), commonly seen in mammograms, correlates with CAC and cardiovascular outcomes. However, whether BAC is associated with AF is unknown. We examined the association of BAC presence and gradation with prevalent or incident AF in the MINERVA cohort of 5,059 post-menopausal women (60-79 years), free of clinical cardiovascular disease, recruited after mammography screening at Kaiser Permanente Northern California between 2012-2015. Incident AF cases were identified between entry and 12/31/2020, and prevalent cases up to 5 years before entry. Both prevalent and incident AF were ascertained using hospital discharge diagnostic and outpatient ICD-9 and ICD-10 codes plus natural language processing of ECG reports and progress notes in the electronic health record. We measured the quantity of BAC using a densitometry method. A total of 469 AF events were ascertained during 6.5 years of follow-up (132 prevalent, 335 incident). In multivariable logistic regression adjusting for age and ethnicity (Model 1), BAC presence (BAC &gt; 0 mg) vs absence (BAC=0 mg) was associated with 1.26 (95% CI:1.02-1.55; p=0.03) increased odds of prevalent or incident AF; further adjustment for body mass index, hypertension, diabetes, cholesterol lowering drugs, anticoagulant use, hs-CRP, e-GFR, sleep apnea and early menopause increased the strength of association between BAC and AF. However, there was no clear dose-response association, although women in the upper tertile of BAC when BAC was present exhibited the highest odds of prevalent or incident AF (adjusted OR=1.91; 95% CI=1.43-2.57; p=&lt;0.001). In sensitivity analysis restricting to incident AF events, the independent association persisted (data not shown). In conclusion, presence of mammographic BAC and more severe BAC may provide additional useful information for AF risk among postmenopausal women.
Association Between Endovascular Therapy Time to Treatment and Outcomes in Patients With Basilar Artery Occlusion
Authors: Raed A. Joundi, Jie-Lena Sun, Ying Xian, Brooke Alhanti, Raul G. Nogueira, Deepak L. Bhatt, Gregg C. Fonarow, Jeffrey Saver, Lee H. Schwamm, Eric E. Smith
Journal: Circulation (2022)

Basilar artery occlusion (BAO) is a devastating condition without definitive evidence to guide treatment. Whereas the association between faster treatment times with endovascular therapy (EVT) and better outcomes in anterior circulation is well established, whether this relationship exists for patients with BAO is not well delineated.We used individual-level patient data from the Get With The Guidelines-Stroke nationwide US registry prospectively collected from January 2015 to December 2019. We identified individuals with BAO treated with EVT within 24 hours of symptom onset. The primary outcomes examined were in-hospital mortality, discharge home, ambulatory at discharge, independent at discharge (modified Rankin Scale score 0 to 2), substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b or 3), and symptomatic intracranial hemorrhage. Using logistic regression models, we evaluated the association between time from symptom onset to treatment with EVT and outcomes.Among 3015 patients with BAO treated with EVT, the mean age was 65.9 years, 38.8% were women, and the median National Institutes of Health Stroke Scale score at presentation was 17 (interquartile range, 8-26). Median onset to EVT time was 406 minutes (interquartile range, 252-688). From 2015 to 2019, there was an overall increase in the median onset to EVT times (380-411 minutes; P=0.016) but no significant change in the proportion of patients treated within 6 hours of symptom onset (48.4%-44.0%; P=0.17). After risk adjustment for patient and hospital-level factors, there were significantly lower odds of in-hospital mortality (adjusted odds ratio [aOR], 0.55 [95% CI, 0.45-0.68]) and symptomatic intracranial hemorrhage (aOR, 0.52 [95% CI, 0.32-0.84]) and significantly higher odds of ambulation at discharge (aOR, 1.72 [95% CI, 1.37-2.16]), discharge home (aOR, 2.19 [95% CI, 1.73-2.77]), and independence at discharge (aOR, 2.21 [95% CI, 1.66-2.95]) when onset to EVT time was ≤6 hours compared with >6 hours. The fastest decay in good outcomes per hour occurred within 6 hours of symptom onset.Among patients receiving EVT for BAO, faster treatment from symptom onset was associated with improved outcomes. These findings support efforts to achieve rapid treatment with EVT for patients with BAO.
18F-FDG and 68Ga-FAPI-04 in the Evaluation of Aggressive Perivascular Epithelioid Cell Tumor
Authors: Zeyu Zhang, Yongwei Yu, Lu Zhang, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

A 10-year-old girl with a right renal mass underwent 18 F-FDG PET/CT and 68 Ga-FAPI-04 PET/MRI for presurgical assessment of tumor invasion and malignant potential. The mass showed low 18 F-FDG uptake and intense 68 Ga-FAPI-04 uptake. Nephrectomy was performed, and the histopathologic diagnosis was aggressive PEComa (perivascular epithelioid cell tumor). This case showed that 68 Ga-FAPI-04 PET outperformed 18 F-FDG PET in detecting aggressive PEComa.
Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy
Authors: Sharon Chinthrajah, Stacie Jones, Edwin Kim, Scott Sicherer, Wayne Shreffler, Bruce Lanser, Negin Atri, Denise Babineau, Daniel Adelman, Ahmar Iqbal, Susan Limb, Amanda Rudman Spergel, Alkis Togias, Robert Wood
Journal: Journal of Allergy and Clinical Immunology (2022)
Concerns about the interpretation of subgroup analysis
Authors: Arthur M. Albuquerque, Carolina B. Santolia, Ashish Verma
Journal: Journal of Clinical Investigation (2021)

We read with interest the article by Li et al. on the association between the use of ACE inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) and in-hospital mortality among patients with .The authors concluded that the use of ARBs was associated with a significant reduction in in-hospital mortality among African American patients but not non-African American patients.However, we believe this conclusion is not per statistical principles and that it potentially misguides readers.As noted by Altman and Bland (2), statistical analysis should be targeted to the clinical question: is the association between ARB use and inhospital mortality different between African American and non-African American patients?To answer this question, one should directly compare the estimates (interaction test; ref.2) performed and reported by the authors.Here we argue that the authors did not accurately interpret this analysis.The authors showed an odds ratio (OR) of 0.196 (95% confidence interval [CI] 0.074-0.516) in the African American population and an OR of 0.687 (95% CI 0.427-1.106) in the non-African American population.Accordingly, the interaction term was not significant (95% CI 0.185-1.292;P = 0.149; ref. 1).As the authors stated that "Statistical significance was defined as a 2-sided P value less than 0.05, unless otherwise stated," the correct interpretation of this result would be that the association of ACE-I/ARB use and in-hospital mortality was not significantly different between these 2 populations (2).In contrast to this interpretation, the authors concluded that the association was only present in the African American population, which is not compatible with their analysis.The potential association between ACE-I/ARB use and COVID-19 in-hospital mortality is of great interest to the medical community.Further, the ability to provide reliable subgroup analyses is vital in clinical decision-making (3).Interaction analyses are essential to answer the clinically relevant question of whether a specific subgroup of patients can benefit more from an intervention than another group.However, we believe the correct interpretation of these results does not support the author's conclusion.
In permanent AF with narrow QRS, AV junction ablation + CRT vs. rate-control drug therapy reduced mortality
Authors: Gaetano Santulli, Pasquale Mone
Journal: Annals of Internal Medicine (2022)

Source Citation Brignole M, Pentimalli F, Palmisano P, et al. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J. 2021;42:4731-9. 34453840
Cyber risks to Ukrainian and other health systems
Authors: Udani Samarasekera
Journal: The Lancet Digital Health (2022)

As of March 14, 2022, WHO estimates that 18 million people in Ukraine have been affected by Russia's military invasion. 6·7 million people are internally displaced and 3 million have fled the country. Alongside this devastating armed conflict is a less visible Russian cyberwar against Ukraine's digital infrastructure, including the health sector. Other countries could also be affected, with warnings issued for the UK and US health-care systems to strengthen their defences against cyber threats from Russia and its allies.
An Ascendant Challenge: Central Nervous System Metastases in <i>ALK</i>+ Lung Cancers
Authors: Yonina R. Murciano-Goroff, Guilherme Harada, Alexander Drilon
Journal: Clinical Cancer Research (2022)

Summary Central nervous system (CNS) metastases constitute a challenge for the design of anaplastic lymphoma kinase (ALK) fusion–positive lung cancer trials. The ASCEND-7 study of ceritinib demonstrates the feasibility of broadening CNS eligibility criteria to include symptomatic brain and leptomeningeal disease and highlights design features that contemporary trials will need to incorporate. See related article by Chow et al., p. 2506
Recruiting a transcription factor in the liver to prevent atherosclerosis
Authors: Alan D. Attie
Journal: Journal of Clinical Investigation (2021)

Hypertriglyceridemia is associated with obesity, diabetes, and atherosclerosis. While lipoprotein lipase (LPL) hydrolyzes triglyceride (TG) cargo into remnant lipoproteins with atherogenic properties, how remnant lipoprotein clearance relates to atherosclerosis in people with diabetes remains unclear. In this issue of the JCI, Shimizu-Albergine et al. examined the effects of the basic leucine zipper transcription factor CREBH, which induces genes that activate LPL in mouse models of type I diabetes. Overexpression of a CREBH fragment reduced apolipoprotein C3 (APOC3) levels, which reduced plasma TGs. Notably, the TGs were lowered by a mechanism that was independent of LPL, and atherosclerosis was alleviated by enhanced lipoprotein remnant clearance as opposed to increased lipolysis of TG-rich lipoprotein precursors. A proinflammatory mechanism likely underlies the atherogenicity of remnant lipoproteins. These findings suggest that modifying CREBH expression in the liver may ameliorate atherosclerosis and, perhaps, other diabetes complications.
Comparison of the safety and immunogenicity of a novel Matrix-M-adjuvanted nanoparticle influenza vaccine with a quadrivalent seasonal influenza vaccine in older adults: a phase 3 randomised controlled trial
Authors: Vivek Shinde, Iksung Cho, Joyce S Plested, Sapeckshita Agrawal, Jamie Fiske, Rongman Cai, Haixia Zhou, Xuan Pham, Mingzhu Zhu, Shane Cloney-Clark, Nan Wang, Bin Zhou, Maggie Lewis, Patty Price-Abbott, Nita Patel, Michael J Massare, Gale Smith, Cheryl Keech, Louis Fries, Gregory M Glenn
Journal: The Lancet Infectious Diseases (2021)
Surgical Issues for Operable Early-Stage Non–Small-Cell Lung Cancer
Authors: Jessica Donington, Lana Schumacher, Jane Yanagawa
Journal: Journal of Clinical Oncology (2022)

Surgical care for early stage non-small-cell lung cancer continuously evolves with new procedures, techniques and care pathways. The most obvious recent change was the transition to minimally invasive procedures, but numerous other aspects of care have also been refined to improve safety and tolerability. These care advancements are essential as we move into an era with increased early detection as a result of screening and greater indications for the use of adjuvant and neoadjuvant strategies.
Abstract P018: Overweight Is Not A Cardiovascular Risk Factor For Insulin-sensitive Individuals: CARDIA 30-year Follow Up
Authors: David P Cistola, Alok Dwivedi
Journal: Circulation (2022)

Introduction: Overweight and obeseare widely reported risk factors for atherosclerotic cardiovascular disease(ASCVD). However, their true impact ondisease risk may be complicated by interactions between measures of adiposityand insulin resistance. Hypothesis: Due to effect modification, the degree towhich overweight or obese increases ASCVD risk depends on fasting insulinstatus. Specific Aim: Determine the effects of overweight and obeseon incident ASCVD by estimating Cox hazard ratios for BMI categories, includingpotential interactions with fasting insulin. Methods: Cox proportional hazards regression models weredeveloped using 30-year follow up datafrom the Coronary Artery Risk Development in Young Adults (CARDIA) study. After excluding participants with baselinediabetes or cardiovascular disease, or those fasting &lt;8 hours or pregnant, atotal of 4,555 subjects were analyzed. The primary outcome was incident ASCVD, defined as any fatal ornon-fatal MI, stroke, TIA, coronary revascularization, non-MI acute coronarysyndrome, CHF, carotid or peripheral artery disease. Cox models were developed, adjusting forcanonical ACC/AHA risk factors and the potential interaction between BMI and fastinginsulin. The reported effect size ishazard ratio (HR) with 95% confidence intervals (CI) and p-values. Results: Cox model 1 adjusted for family history ofpremature ASCVD, metabolic syndrome criteria, LDL-C &gt;160 mg/dL, nicotine use(serum cotinine), chronic kidney disease (eGFR&lt;60), history of earlymenopause, fitness level by treadmill, race, fasting insulin and BMI category. In model 1, both overweight (HR 1.46, 95% CI:1.07, 1.99; p=0.0158) and obese (HR 2.21, 95% CI: 1.52, 3.21; p&lt;0.0001) appearedto be independently associated with incident ASCVD. Cox model 2 included an interacting categoricalvariable that included both BMI andfasting insulin. In model 2, overweightwas not a risk factor for CARDIA participants with fasting insulin values inthe lower half (&lt;9.0 μIU/mL): HR 1.36, 95% CI: 0.81,2.30, p=0.2482. However, overweight wasa significant risk factor for those with fasting insulin in the upperhalf: HR 2.21, 95% CI: 1.51, 3.24, p&lt;0.0001. This result was cross-checked and confirmed using otherwise identical modelsstratified by fasting insulin level. Thehazard ratios were 1.34 (95% CI: 0.79, 2.27, p=0.2818) for normoinsulinemic,overweight individuals and 1.51 (95% CI 1.03, 2.21, p=0.0367) forhyperinsulinemic, overweight individuals, as compared with those with BMI&lt;25. In contrast to overweight, obese was anindependent risk factor for ASCVD regardless of fasting insulin status. Conclusion: Overweight was not an ASCVD risk factor forCARDIA participants with low fasting insulin. If confirmed, these findings could inform tailored weight-lossrecommendations for overweight individuals.
Why the world has no universal biosafety standards
Journal: BMJ (2022)

WHO advises that the following description in the original article did not properly represent WHO's (and the World Organisation for Animal Health's) present position: "WHO classifies micro-organisms into four risk groups, and laboratories into corresponding safety levels, with 4 the highest risk."WHO explains that these notions were abolished in the publication of the WHO Laboratory Biosafety Manual 4th edition (LBM4), which promotes an evidence based and risk based approach, as opposed to such static and pre-defined classifications.The sentence has been amended in the online version of the BMJ article as follows: "WHO previously classified micro-organisms into four risk groups, and laboratories into corresponding safety levels, with 4 the highest risk.
A Case of Brown Tumor on 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT
Authors: Xilan Yao, Xiaohong Ou
Journal: Clinical Nuclear Medicine (2021)

Abstract A 50-year-old man presented with right chest pain and persistent increased parathyroid hormone after parathyroidectomy for parathyroid carcinoma. 68 Ga-DOTATATE PET/CT and 18 F-FDG PET/CT were performed consecutively for restaging to determine subsequent treatment strategy. An osteolytic lesion on the right sixth rib showed increased uptake on both 68 Ga-DOTATATE and 18 F-FDG PET/CT. Subsequent biopsy confirmed it to be a brown tumor.