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Souza INO, Roychaudhuri R, de Belleroche J, and Mothet JP
Trends in molecular medicine [Trends Mol Med] 2023 Dec; Vol. 29 (12), pp. 1014-1028. Date of Electronic Publication: 2023 Sep 26.
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Humans, Critical Pathways, Central Nervous System metabolism, Brain metabolism, Amino Acids metabolism, and Alzheimer Disease metabolism
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Free d-amino acids (d-AAs) are emerging as a novel and important class of signaling molecules in many organs, including the brain and endocrine systems. There has been considerable progress in our understanding of the fundamental roles of these atypical messengers, with increasingly recognized implications in a wide range of neuropathologies, including schizophrenia (SCZ), epilepsy, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), substance abuse, and chronic pain, among others. Research has enabled the discovery that d-serine, d-aspartate and more recently d-cysteine are essential for the healthy development and function of the central nervous system (CNS). We discuss recent progress that has profoundly transformed our vision of numerous physiological processes but has also shown how d-AAs are now offering therapeutic promise in clinical settings for several human diseases.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
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Daix, Thomas, Mathonnet, Armelle, Brakenridge, Scott, Dequin, Pierre-François, Mira, Jean-Paul, Berbille, Frederique, Morre, Michel, Jeannet, Robin, Blood, Teresa, Unsinger, Jacqueline, Blood, Jane, Walton, Andrew, Moldawer, Lyle L., Hotchkiss, Richard, and Francois, Bruno
- Annals of Intensive Care. December, 2023, Vol. 13 Issue 1
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Sidik NP, Stanley B, Sykes R, Morrow AJ, Bradley CP, McDermott M, Ford TJ, Roditi G, Hargreaves A, Stobo D, Adams J, Byrne J, Mahrous A, Young R, Carrick D, McGeoch R, Corcoran D, Lang NN, Heggie R, Wu O, McEntegart MB, McConnachie A, and Berry C
Circulation [Circulation] 2023 Oct 05. Date of Electronic Publication: 2023 Oct 05.
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Background: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries.
Methods: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 μg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes.
Results: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P <0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P <0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P =0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P =0.013).
Conclusions: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved.
Registration: URL: https://www.
Clinicaltrials: gov; Unique identifier: NCT03477890.
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Masheb RM, Vernarelli JA, Snow JL, Marsh AG, Ciszewski S, Dudley B, White CA, Purcell SA, and Lutes L
Clinical nutrition ESPEN [Clin Nutr ESPEN] 2023 Oct; Vol. 57, pp. 735-738. Date of Electronic Publication: 2023 Aug 24.
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United States, Female, Humans, Adolescent, Young Adult, Adult, Male, Databases, Factual, Diet, and Food
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Background & Aims: Brief screening questionnaires can identify 'at risk' behaviors in clinical settings. However, there is currently no screener for dietary intake specifically developed using foods associated with body weight change and increased risk for multiple chronic conditions and diseases.
Methods: We developed a novel brief dietary screener, the 24-Hour Food Frequency Assessment Screening Tool Questionnaire (FAST24), to identify intake of foods associated with weight change. University students completed the FAST24 and the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) at two time points to assess acceptability and determine preliminary criterion validity against food categories from the United States Department of Agriculture (USDA) Food Patterns Equivalents Database (FPED).
Results: 202 individuals (age 20.4 ± 3.6 years; 65.7% females) completed the FAST24 in an average time of 2 min compared to 24 min for the ASA24. Over half of the food items from the FAST24 were matched to, and correlated with, standard USDA food pattern components (r's ranging from .15 to .58, p's < .05). Food items from the dietary data from the FAST24 were also highly correlated with the more intensive ASA24 application (r's ranging from .23 to .82, p's < .01), and were less time-consuming and burdensome to complete (p's < .0001).
Conclusions: Findings support the continued refinement of the FAST24 as a rapid, valid primary care assessment tool for measuring USDA dietary intake patterns. Use of a short, simple screener such as the FAST24 has the potential for integration into large healthcare delivery settings to help establish a baseline for promoting relative behavior changes critical for long-term health and well-being.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Published by Elsevier Ltd.)
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van der Kruk S, Harrison NJ, Bartram A, Newton S, Miller C, Room R, Olver I, and Bowden J
Health promotion international [Health Promot Int] 2023 Oct 01; Vol. 38 (5).
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Parental supply of alcohol to minors (i.e. those under the legal drinking age) is often perceived by parents as protective against harms from drinking, despite evidence linking it with adverse alcohol-related outcomes. This systematic review describes the prevalence of parental supply of alcohol, as reported in the international literature. The review was registered with PROSPERO (CRD42020218754). We searched seven online databases (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science and Public Health Database) and grey literature from January 2011 to December 2022 and assessed the risk of bias with the JBI Critical Appraisal Checklist. Among 58 articles included in narrative synthesis from 29 unique datasets, there was substantial variation in the definition and measurement of parental supply of alcohol. Overall prevalence rates ranged from 7.0 to 60.0% for minor-report samples, and from 24.0 to 8.0% for parent-report samples. Data indicate that parental supply prevalence is generally proportionately higher for older minors or later-stage students, for girls, and has increased over time among minors who report drinking. Literature on the prevalence of parental supply of alcohol is robust in quantity but inconsistent in quality and reported prevalence. Greater consistency in defining and measuring parental supply is needed to better inform health promotion initiatives aimed at increasing parents' awareness.
(© The Author(s) 2023. Published by Oxford University Press.)
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Scott JV, Moutchia J, McClelland RL, Al-Naamani N, Weinberg E, Palevsky HI, Minhas J, Appleby DK, Smith A, Pugliese SC, Ventetuolo CE, and Kawut SM
MedRxiv : the preprint server for health sciences [medRxiv] 2023 Sep 30. Date of Electronic Publication: 2023 Sep 30.
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Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are disorders of the pulmonary vasculature that cause right ventricular dysfunction. Systemic consequences of right ventricular dysfunction include damage to other solid organs, such as the liver. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied.
Methods: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2012. We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity.
Results: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with complete liver laboratory panels (serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin). Using k-means clustering paired with factor analysis, we identified four unique liver phenotypes (no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns). Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and highest chance of worsening World Health Organization functional class. Randomization to the experimental arm was associated with a transition to healthier liver clusters compared to randomization to the control arm. The cholestatic injury group experienced the greatest placebo-corrected treatment benefit in terms of six-minute walk distance.
Conclusions: Liver injury patterns were associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment of pulmonary hypertension in these clinical trials had beneficial effects on liver health compared to placebo. The independent role of liver disease (often subclinical) in determining outcomes warrants prospective studies of the clinical utility of liver phenotyping for PAH prognosis and contribution to clinical disease.
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Lutz J, Pratap A, Lenze EJ, Bestha D, Lipschitz JM, Karantzoulis S, Vaidyanathan U, Robin J, Horan W, Brannan S, Mittoux A, Davis MC, Lakhan SE, and Keefe R
Innovations in clinical neuroscience [Innov Clin Neurosci] 2023 Sep 01; Vol. 20 (7-9), pp. 40-46. Date of Electronic Publication: 2023 Sep 01 (Print Publication: 2023).
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Objective: Recruitment of a sufficiently large and representative patient sample and its retention during central nervous system (CNS) trials presents major challenges for study sponsors. Technological advances are reshaping clinical trial operations to meet these challenges, and the COVID-19 pandemic further accelerated this development.
Method of Research: The International Society for CNS Clinical Trials and Methodology (ISCTM; www.isctm.org) Innovative Technologies for CNS Trials Working Group surveyed the state of technological innovations for improved recruitment and retention and assessed their promises and pitfalls.
Results: Online advertisement and electronic patient registries can enhance recruitment, but challenges with sample representativeness, conversion rates from eligible prescreening to enrolled patients, data privacy and security, and patient identification remain hurdles for optimal use of these technologies. Electronic medical records (EMR) mining with artificial intelligence (AI)/machine learning (ML) methods is promising but awaits translation into trials. During the study treatment phase, technological innovations increasingly support participant retention, including adherence with the investigational treatment. Digital tools for adherence and retention support take many forms, including patient-centric communication channels between researchers and participants, real-time study reminders, and digital behavioral interventions to increase study compliance. However, such tools add technical complexities to trials, and their impact on the generalizability of results are largely unknown.
Conclusion: Overall, the group found a scarcity of systematic data directly assessing the impact of technological innovations on study recruitment and retention in CNS trials, even for strategies with already high adoption, such as online recruitment. Given the added complexity and costs associated with most technological innovations, such data is needed to fully harness technologies for CNS trials and drive further adoption.
Competing Interests: DISCLOSURES: Dr. Lutz may have equity interests with Click Therapeutics, Inc. Dr. Lenze has previously consulted for Merck, Prodeo, Boehringer Ingelheim, Pritikin ICR, and IngenioRx; he has previously received funding from PCORI, the COVID-19 Early Treatment Fund, Mercatus/FastGrants, and Janssen; and he has a patent pending for sigma1 receptor agonists for COVID-19 treatment. Dr. Vaidyanathan was an employee of Boehringer Ingelheim at the time of writing. Dr. Robin is an employee of Winterlight Labs, Inc. and has equity interests with Winterlight Labs, Inc. Dr. Horan was an employee of WCG VeraSci at the time of writing, and is now an employee of Karuna Therapeutics. Dr. Brannan is an employee at Karuna Therapeutics. Dr. Lakhan is employed by Click Therapeutics, Inc. and has equity interests. Dr. Keefe serves as a paid consultant to WCG, Karuna, Merck, Sunovion, Biogen, and Boehringer Ingelheim. All other authors have no conflicts of interest relevant to the contents of this article.
(Copyright © 2023. Matrix Medical Communications. All rights reserved.)
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Vos JL, Raafs AG, Henkens MTHM, Pedrizzetti G, van Deursen CJ, Rodwell L, Heymans SRB, and Nijveldt R
European heart journal. Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2023 Aug 23; Vol. 24 (9), pp. 1231-1240.
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Humans, Contrast Media, Ventricular Pressure, Magnetic Resonance Imaging, Cine, Gadolinium, Ventricular Function, Left, Stroke Volume, Magnetic Resonance Spectroscopy, Prognosis, Predictive Value of Tests, and Cardiomyopathy, Dilated
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Aims: Left ventricular (LV) blood flow is determined by intraventricular pressure gradients (IVPG). Changes in blood flow initiate remodelling and precede functional decline. Novel cardiac magnetic resonance (CMR) post-processing LV-IVPG analysis might provide a sensitive marker of LV function in dilated cardiomyopathy (DCM). Therefore, the aim of our study was to evaluate LV-IVPG patterns and their prognostic value in DCM.
Methods and Results: LV-IVPGs between apex and base were measured on standard CMR cine images in DCM patients (n = 447) from the Maastricht Cardiomyopathy registry. Major adverse cardiovascular events, including heart failure hospitalisations, life-threatening arrhythmias, and sudden/cardiac death, occurred in 66 DCM patients (15%). A temporary LV-IVPG reversal during systolic-diastolic transition, leading to a prolonged transition period or slower filling, was present in 168 patients (38%). In 14%, this led to a reversal of blood flow, which predicted outcome corrected for univariable predictors [hazard ratio (HR) = 2.57, 95% confidence interval (1.01-6.51), P = 0.047]. In patients without pressure reversal (n = 279), impaired overall LV-IVPG [HR = 0.91 (0.83-0.99), P = 0.033], systolic ejection force [HR = 0.91 (0.86-0.96), P < 0.001], and E-wave decelerative force [HR = 0.83 (0.73-0.94), P = 0.003] predicted outcome, independent of known predictors (age, sex, New York Heart Association class ≥ 3, LV ejection fraction, late gadolinium enhancement, LV-longitudinal strain, left atrium (LA) volume-index, and LA-conduit strain).
Conclusion: Pressure reversal during systolic-diastolic transition was observed in one-third of DCM patients, and reversal of blood flow direction predicted worse outcome. In the absence of pressure reversal, lower systolic ejection force, E-wave decelerative force (end of passive LV filling), and overall LV-IVPG are powerful predictors of outcome, independent of clinical and imaging parameters.
Competing Interests: Conflict of interest: None declared.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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Lee H, Wiggermann V, Rauscher A, Kames C, Beg MF, Popuri K, Tam R, Lam K, Jacova C, Shahinfard E, Sossi V, Pettersen JA, and Hsiung GR
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques [Can J Neurol Sci] 2023 Jul; Vol. 50 (4), pp. 515-528. Date of Electronic Publication: 2022 May 26.
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Humans, Diffusion Tensor Imaging, Cross-Sectional Studies, Brain diagnostic imaging, Brain pathology, Magnetic Resonance Imaging methods, Dementia, Vascular diagnostic imaging, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology, and Mixed Dementias
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Background: A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.
Objective: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.
Methods: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.
Results: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).
Conclusion: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.
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Raafs AG, Vos JL, Henkens MTHM, Verdonschot JAJ, Sikking M, Stroeks S, Gerretsen S, Hazebroek MR, Knackstedt C, Nijveldt R, and Heymans SRB
JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2023 Jul; Vol. 16 (7), pp. 991-992. Date of Electronic Publication: 2023 Mar 08.
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Humans, Predictive Value of Tests, Heart Atria diagnostic imaging, Echocardiography, Atrial Fibrillation diagnostic imaging, Atrial Fibrillation etiology, and Cardiomyopathy, Dilated diagnostic imaging
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11. Author Correction: The power of genetic diversity in genome-wide association studies of lipids. [2023]
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Graham SE, Clarke SL, Wu KH, Kanoni S, Zajac GJM, Ramdas S, Surakka I, Ntalla I, Vedantam S, Winkler TW, Locke AE, Marouli E, Hwang MY, Han S, Narita A, Choudhury A, Bentley AR, Ekoru K, Verma A, Trivedi B, Martin HC, Hunt KA, Hui Q, Klarin D, Zhu X, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Ruotsalainen SE, Havulinna AS, Veturi Y, Feng Q, Rosenthal EA, Lingren T, Pacheco JA, Pendergrass SA, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Hindy G, Rasheed A, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Willemsen G, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Yao J, Manichaikul A, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Sidore C, Fiorillo E, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Thuesen BH, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Feitosa MF, Wojczynski MK, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Kember RL, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Leonard HL, Marten J, Schmidt B, Arendt M, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Ahmed M, Jackson AU, Yousri NA, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Chai X, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Hung YJ, Chen S, Liu F, Yang J, Kentistou KA, Gorski M, Brumat M, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Xue C, Zhang J, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, Lee J, van der Laan SW, Chitrala KN, Weiss S, Zimmermann ME, Lee JY, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hildalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Schwander K, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Highland HM, Young KL, Kawaguchi T, Thiery J, Bis JC, Nadkarni GN, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, Bhatti KF, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Chen YE, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Kato N, Schulze MB, Girotto G, Jung B, Böger CA, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Yajnik CS, Mercader JM, Tusié-Luna T, Aguilar-Salinas CA, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Lu F, Qu J, Hishigaki H, Lin X, März W, Parra EJ, Cruz M, Gudnason V, Tardif JC, Lettre G, 't Hart LM, Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Psaty BM, Brandslund I, Pramstaller PP, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Cucca F, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Justice AE, Baras A, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Thorsteinsdottir U, Stefansson K, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Rotimi CN, Hazelhurst S, Ramsay M, Trembath RC, van Heel DA, Tamiya G, Yamamoto M, Kim BJ, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Natarajan P, Peloso GM, Brown CD, Morris AP, Assimes TL, Deloukas P, Sun YV, and Willer CJ
Nature [Nature] 2023 Jun; Vol. 618 (7965), pp. E19-E20.
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Henkens MTHM, Raafs AG, Vanloon T, Vos JL, Vandenwijngaard A, Brunner HG, Krapels IPC, Knackstedt C, Gerretsen S, Hazebroek MR, Vernooy K, Nijveldt R, Lumens J, and Verdonschot JAJ
Journal of cardiac failure [J Card Fail] 2023 May 23. Date of Electronic Publication: 2023 May 23.
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Background: Truncating variants in titin (TTNtv) are the most prevalent genetic etiology of dilated cardiomyopathy (DCM). Although TTNtv has been associated with atrial fibrillation, it remains unknown whether and how left atrial (LA) function differs between patients with DCM with and without TTNtv. We aimed to determine and compare LA function in patients with DCM with and without TTNtv and to evaluate whether and how left ventricular (LV) function affects the LA using computational modeling.
Methods and Results: Patients with DCM from the Maastricht DCM registry that underwent genetic testing and cardiovascular magnetic resonance (CMR) were included in the current study. Subsequent computational modeling (CircAdapt model) was performed to identify potential LV and LA myocardial hemodynamic substrates. In total, 377 patients with DCM (n = 42 with TTNtv, n = 335 without a genetic variant) were included (median age 55 years, interquartile range [IQR] 46-62 years, 62% men). Patients with TTNtv had a larger LA volume and decreased LA strain compared with patients without a genetic variant (LA volume index 60 mLm -2 [IQR 49-83] vs 51 mLm -2 [IQR 42-64]; LA reservoir strain 24% [IQR 10-29] vs 28% [IQR 20-34]; LA booster strain 9% [IQR 4-14] vs 14% [IQR 10-17], respectively; all P < .01). Computational modeling suggests that while the observed LV dysfunction partially explains the observed LA dysfunction in the patients with TTNtv, both intrinsic LV and LA dysfunction are present in patients with and without a TTNtv.
Conclusions: Patients with DCM with TTNtv have more severe LA dysfunction compared with patients without a genetic variant. Insights from computational modeling suggest that both intrinsic LV and LA dysfunction are present in patients with DCM with and without TTNtv.
Competing Interests: Declaration of Competing Interest The authors have no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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Thompson J, Teasdale B, van Emde Boas E, Budelmann F, Duncan S, Maguire L, and Dunbar R
Frontiers in psychology [Front Psychol] 2023 May 15; Vol. 14, pp. 1159866. Date of Electronic Publication: 2023 May 15 (Print Publication: 2023).
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Introduction: The human capacity to engage with fictional worlds raises important psychological questions about the mechanisms that make this possible. Of particular interest is whether people respond differently to fictional stories compared to factual ones in terms of how immersed they become and how they view the characters involved and their actions. It has been suggested that fiction provides us with a 'fictive pass' that allows us to evaluate in a more balanced, detached way the morality of a character's behaviour.
Methods: We use a randomised controlled experimental design to test this.
Results and Discussion: We show that, although knowing whether a substantial film clip is fact or fiction does not affect how engaged with ('transported' by) a troubling story an observer becomes, it does grant them a 'fictive pass' to empathise with a moral transgressor. However, a fictive pass does not override the capacity to judge the causes of a character's moral transgression (at least as indexed by a causal attribution task).
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Thompson, Teasdale, van Emde Boas, Budelmann, Duncan, Maguire and Dunbar.)
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Gross R, Thaweethai T, Rosenzweig EB, Chan J, Chibnik LB, Cicek MS, Elliott AJ, Flaherman VJ, Foulkes AS, Witvliet MG, Gallagher R, Gennaro ML, Jernigan TL, Karlson EW, Katz SD, Kinser PA, Kleinman LC, Lamendola-Essel MF, Milner JD, Mohandas S, Mudumbi PC, Newburger JW, Rhee KE, Salisbury AL, Snowden JN, Stein CR, Stockwell MS, Tantisira KG, Thomason ME, Truong DT, Warburton D, Wood JC, Ahmed S, Akerlundh A, Alshawabkeh AN, Anderson BR, Aschner JL, Atz AM, Aupperle RL, Baker FC, Balaraman V, Banerjee D, Barch DM, Baskin-Sommers A, Bhuiyan S, Bind MC, Bogie AL, Buchbinder NC, Bueler E, Bükülmez H, Casey BJ, Chang L, Clark DB, Clifton RG, Clouser KN, Cottrell L, Cowan K, D'Sa V, Dapretto M, Dasgupta S, Dehority W, Dummer KB, Elias MD, Esquenazi-Karonika S, Evans DN, Faustino EVS, Fiks AG, Forsha D, Foxe JJ, Friedman NP, Fry G, Gaur S, Gee DG, Gray KM, Harahsheh AS, Heath AC, Heitzeg MM, Hester CM, Hill S, Hobart-Porter L, Hong TKF, Horowitz CR, Hsia DS, Huentelman M, Hummel KD, Iacono WG, Irby K, Jacobus J, Jacoby VL, Jone PN, Kaelber DC, Kasmarcak TJ, Kluko MJ, Kosut JS, Laird AR, Landeo-Gutierrez J, Lang SM, Larson CL, Lim PPC, Lisdahl KM, McCrindle BW, McCulloh RJ, Mendelsohn AL, Metz TD, Morgan LM, Müller-Oehring EM, Nahin ER, Neale MC, Ness-Cochinwala M, Nolan SM, Oliveira CR, Oster ME, Payne RM, Raissy H, Randall IG, Rao S, Reeder HT, Rosas JM, Russell MW, Sabati AA, Sanil Y, Sato AI, Schechter MS, Selvarangan R, Shakti D, Sharma K, Squeglia LM, Stevenson MD, Szmuszkovicz J, Talavera-Barber MM, Teufel RJ 2nd, Thacker D, Udosen MM, Warner MR, Watson SE, Werzberger A, Weyer JC, Wood MJ, Yin HS, Zempsky WT, Zimmerman E, and Dreyer BP
MedRxiv : the preprint server for health sciences [medRxiv] 2023 May 12. Date of Electronic Publication: 2023 May 12.
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Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.
Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.
Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.
Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.
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Sheridan, Nicolette, Love, Tom, Kenealy, Timothy, Aguirre-Duarte, Nelson, Arroll, Bruce, Atmore, Carol, Carryer, Jenny, Crampton, Peter, Dowell, Anthony, Fishman, Tana, Gauld, Robin, Harwood, Matire, Hoare, Karen, Jackson, Gary, Jansen, Rawiri McKree, Kerse, Ngaire, Lampshire, Debra, McBain, Lynn, MacRae, Jayden, Mills, Jane, Øvretveit, John, Percival, Teuila, Perera, Roshan, Roland, Martin, Ryan, Debbie, Schmidt-Busby, Jacqueline, Stokes, Tim, Stubbe, Maria, Hewitt, Sarah, Watt, Daniel, and Peck, Chris
- International Journal for Equity in Health. May 4, 2023, Vol. 22 Issue 1
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Zannad F, Alikhaani J, Alikhaani S, Butler J, Gordon J, Jensen K, Khatib R, Mantovani L, Martinez R, Moore WF, Murakami M, Roessig L, Stockbridge N, Van Spall HGC, Yancy C, and Spertus JA
European journal of heart failure [Eur J Heart Fail] 2023 Apr; Vol. 25 (4), pp. 478-487. Date of Electronic Publication: 2023 Mar 22.
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Humans, Patient Participation, Patient Reported Outcome Measures, Caregivers, Quality of Life, and Heart Failure therapy
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There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This 'minimal clinically important difference' requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.
(© 2023 European Society of Cardiology.)
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Petrovic B, Bender JL, Liddy C, Afkham A, McGee SF, Morgan SC, Segal R, O'Brien MA, Julian JA, Sussman J, Urquhart R, Fitch M, Schneider ND, and Grunfeld E
Current oncology (Toronto, Ont.) [Curr Oncol] 2023 Mar 21; Vol. 30 (3), pp. 3537-3548. Date of Electronic Publication: 2023 Mar 21.
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Humans, Continuity of Patient Care, Surveys and Questionnaires, Communication, Internet, and Neoplasms therapy
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Healthcare providers have reported challenges with coordinating care for patients with cancer. Digital technology tools have brought new possibilities for improving care coordination. A web- and text-based asynchronous system (eOncoNote) was implemented in Ottawa, Canada for cancer specialists and primary care providers (PCPs). This study aimed to examine PCPs' experiences of implementing eOncoNote and how access to the system influenced communication between PCPs and cancer specialists. As part of a larger study, we collected and analyzed system usage data and administered an end-of-discussion survey to understand the perceived value of using eOncoNote. eOncoNote data were analyzed for 76 shared patients (33 patients receiving treatment and 43 patients in the survivorship phase). Thirty-nine percent of the PCPs responded to the cancer specialist's initial eOncoNote message and nearly all of those sent only one message. Forty-five percent of the PCPs completed the survey. Most PCPs reported no additional benefits of using eOncoNote and emphasized the need for electronic medical record (EMR) integration. Over half of the PCPs indicated that eOncoNote could be a helpful service if they had questions about a patient. Future research should examine opportunities for EMR integration and whether additional interventions could support communication between PCPs and cancer specialists.
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Lucas, Jacqueline, Villarroel, Maria, and Cohen, Robin
MMWR: Morbidity & Mortality Weekly Report . 3/3/2023, Vol. 72 Issue 9, p244-244. 1p. 1 Graph.
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TELEMEDICINE, MEDICAL personnel, and PUBLIC health
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The article analysis the statistics related to telemedicine visit with a health care professional.
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19. Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing. [2023]
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Baliga S, Adams JA, Bajaj BVM, Van Benthuysen L, Daartz J, Gallotto SL, Lewy JR, DeNunzio N, Weyman EA, Lawell MP, Palmer JD, Yeap BY, Ebb DH, Huang MS, Perry AF, MacDonald SM, Jones RM, Tarbell NJ, and Yock TI
Cancer [Cancer] 2023 Mar 01; Vol. 129 (5), pp. 764-770. Date of Electronic Publication: 2022 Dec 11.
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Humans, Child, Organ Sparing Treatments methods, Organs at Risk, Protons, Prospective Studies, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy Dosage, Cranial Irradiation adverse effects, Cranial Irradiation methods, Neoplasm Recurrence, Local epidemiology, Hippocampus diagnostic imaging, Medulloblastoma radiotherapy, Brain Neoplasms radiotherapy, Brain Neoplasms secondary, Radiotherapy, Intensity-Modulated methods, and Cerebellar Neoplasms radiotherapy
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Background: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB).
Methods and Materials: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans.
Results: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.
Conclusions: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.
Plain Language Summary: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.
(© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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Groenewold NA, Bas-Hoogendam JM, Amod AR, Laansma MA, Van Velzen LS, Aghajani M, Hilbert K, Oh H, Salas R, Jackowski AP, Pan PM, Salum GA, Blair JR, Blair KS, Hirsch J, Pantazatos SP, Schneier FR, Talati A, Roelofs K, Volman I, Blanco-Hinojo L, Cardoner N, Pujol J, Beesdo-Baum K, Ching CRK, Thomopoulos SI, Jansen A, Kircher T, Krug A, Nenadić I, Stein F, Dannlowski U, Grotegerd D, Lemke H, Meinert S, Winter A, Erb M, Kreifelts B, Gong Q, Lui S, Zhu F, Mwangi B, Soares JC, Wu MJ, Bayram A, Canli M, Tükel R, Westenberg PM, Heeren A, Cremers HR, Hofmann D, Straube T, Doruyter AGG, Lochner C, Peterburs J, Van Tol MJ, Gur RE, Kaczkurkin AN, Larsen B, Satterthwaite TD, Filippi CA, Gold AL, Harrewijn A, Zugman A, Bülow R, Grabe HJ, Völzke H, Wittfeld K, Böhnlein J, Dohm K, Kugel H, Schrammen E, Zwanzger P, Leehr EJ, Sindermann L, Ball TM, Fonzo GA, Paulus MP, Simmons A, Stein MB, Klumpp H, Phan KL, Furmark T, Månsson KNT, Manzouri A, Avery SN, Blackford JU, Clauss JA, Feola B, Harper JC, Sylvester CM, Lueken U, Veltman DJ, Winkler AM, Jahanshad N, Pine DS, Thompson PM, Stein DJ, and Van der Wee NJA
Molecular psychiatry [Mol Psychiatry] 2023 Mar; Vol. 28 (3), pp. 1079-1089. Date of Electronic Publication: 2023 Jan 19.
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Adult, Adolescent, Humans, Magnetic Resonance Imaging methods, Brain, Anxiety, Neuroimaging methods, and Phobia, Social
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There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE = 0.037; right: d = -0.104, p FWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE < 0.001; right: d = -0.158, p FWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE = 0.006; right: d = 0.099, p FWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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Dieleman E, van der Woude L, van Os R, van Bockel L, Coremans I, van Es C, De Jaeger K, Knol HP, Kolff W, Koppe F, Pomp J, Reymen B, Schinagl D, Spoelstra F, Tissing-Tan C, van der Voort van Zyp N, van der Wel A, Wijsman R, Dielwart M, Wiegman E, Damhuis R, and Belderbos J
Clinical lung cancer [Clin Lung Cancer] 2023 Mar; Vol. 24 (2), pp. 130-136. Date of Electronic Publication: 2022 Nov 25.
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Humans, Male, Aged, Infant, Neoplasm Staging, Chemoradiotherapy adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, and Radiation Oncology
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Introduction: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.
Methods: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.
Results: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.
Conclusion: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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Follmann, Dean, Janes, Holly E., Chu, Eric, Jayashankar, Lakshmi, Petropoulos, Christos J., Serebryannyy, Leonid, Carroll, Robin, Jean-Baptiste, Naz, Narpala, Sandeep, Lin, Bob C., McDermott, Adrian, Novak, Richard M., Graciaa, Daniel S., Rolsma, Stephanie, Magaret, Craig A., Doria-Rose, Nicole, Corey, Lawrence, Neuzil, Kathleen M., Pajon, Rolando, Miller, Jacqueline M., Donis, Ruben O., Koup, Richard A., Baden, Lindsey R., and Sahly, Hana M. El
- Open Forum Infectious Diseases. March, 2023, Vol. 10 Issue 3
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Butcher SC, Vos JL, Fortuni F, Galloo X, Liem SIE, Bax JJ, Delgado V, Vonk MC, van Leuven SI, Snoeren M, El Messaoudi S, de Vries-Bouwstra JK, Nijveldt R, and Ajmone Marsan N
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2023 Feb 06; Vol. 62 (SI), pp. SI20-SI31.
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Female, Humans, Male, Contrast Media, Gadolinium, Magnetic Resonance Imaging, Cine, Magnetic Resonance Spectroscopy, Predictive Value of Tests, Prognosis, Stroke Volume, Ventricular Function, Left, Middle Aged, Heart Failure, Scleroderma, Systemic complications, and Scleroderma, Systemic diagnostic imaging
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Objective: This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc.
Methods: A total of 100 patients {54 [interquartile range (IQR) 46-64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality.
Results: The median LV GLS was -21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P = 0.049] was independently associated with New York Heart Association (NYHA) class II-IV heart failure symptoms. Over a median follow-up of 37 (21-62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement.
Conclusion: In patients with SSc, LARS was independently associated with the presence of NYHA class II-IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
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Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng WH, Zhou Y, Hoffman D, Harb JG, Potluri J, and Garcia-Manero G
American journal of hematology [Am J Hematol] 2023 Feb; Vol. 98 (2), pp. 272-281. Date of Electronic Publication: 2022 Nov 10.
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Aged, Humans, Male, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Neutropenia chemically induced, Sulfonamides, Treatment Outcome, Female, Antineoplastic Combined Chemotherapy Protocols adverse effects, and Myelodysplastic Syndromes drug therapy
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Patients with relapsed/refractory (R/R) higher-risk myelodysplastic syndromes (MDS) have a dismal median overall survival (OS) after failing hypomethylating agent (HMA) treatment. There is no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies. Herein, we present the safety and efficacy of venetoclax + azacitidine in patients with R/R MDS. This phase 1b, open-label, multicenter study enrolled patients ≥18 years. Patients were treated with escalating doses of oral venetoclax: 100, 200, or 400 mg daily for 14 days every 28-day cycle. Azacitidine was administered on Days 1-7 every cycle at 75 mg/m 2 /day intravenously/subcutaneously. Responses were assessed per modified 2006 International Working Group (IWG) criteria. Forty-four patients (male 86%, median age 74 years) received venetoclax + azacitidine treatment. Median follow-up was 21.2 months. Hematological adverse events of Grade ≥ 3 included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%). Pneumonia (23%) was the most common Grade ≥ 3 infection. Marrow responses were seen including complete remission (CR, n = 3, 7%) and marrow CR (mCR, n = 14, 32%); 36% (16/44) achieved transfusion independence (TI) for RBCs and/or platelets, and 43% (6/14) with mCR achieved hematological improvement (HI). The median time to CR/mCR was 1.2 months, and the median duration of response for CR + mCR was 8.6 months. Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.
(© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
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Cruzado-Quiñones J, Huibregtse RC, and Jordan AO
Journal of correctional health care : the official journal of the National Commission on Correctional Health Care [J Correct Health Care] 2023 Feb; Vol. 29 (1), pp. 19-26. Date of Electronic Publication: 2023 Jan 25.
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Female, Humans, New York City, Puerto Rico, Transgender Persons, Male, Hispanic or Latino, and Health Services for Transgender Persons
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Transitional Care Coordination is an evidence-informed model program developed by New York City Correctional Health Services as a Health Resources and Services Administration Special Projects of National Significance Correctional Health Linkage Intervention. Using implementation science under this and subsequent demonstration projects, interventions were adapted and enhanced to address the transitional needs of people of Puerto Rican ancestry and to expand the network of care across the islands of Puerto Rico. These interventions were informed, in part, by a transnational trans woman of color of Puerto Rican ancestry living with HIV. A socioecological model framework and case study are used to illustrate how evidence-informed interventions are developed and adapted to address the needs of those served.
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Alasfar S, Chiang TP, Snyder AJ, Ou MT, Boyarsky BJ, Abedon AT, Alejo JL, Cook S, Cochran W, Brigham E, Parker AM, Garonzik-Wang J, Massie AB, Brennan DC, Vannorsdall T, Segev DL, and Avery RK
Transplantation [Transplantation] 2023 Jan 01; Vol. 107 (1), pp. 181-191. Date of Electronic Publication: 2022 Sep 19.
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Humans, Self Report, SARS-CoV-2, Quality of Life, COVID-19 Testing, Transplant Recipients, Cough, Pain, COVID-19 epidemiology, and Organ Transplantation adverse effects
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Background: Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization.
Methods: A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration.
Results: Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%).
Conclusions: SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.
(Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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Mitchell J, Chiang TP, Alejo JL, Kim JD, Chang A, Abedon AT, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Segev DL, Massie AB, and Werbel WA
Clinical transplantation [Clin Transplant] 2023 Jan; Vol. 37 (1), pp. e14868. Date of Electronic Publication: 2022 Dec 07.
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Humans, COVID-19 Vaccines, Kinetics, SARS-CoV-2, Antibodies, Transplant Recipients, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation
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Brown, Stewart, Bailey, Janice, Wang, Robin, Kemp, Jacqueline, Strawbridge, Martyn, Sheppard, Mary, Dayer, Mark J., and Furniss, Guy O.
- Heart rhythm. 20(S):S117-S118
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Raafs, Anne G., Vos, Jacqueline L., Henkens, Michiel T.H.M., Verdonschot, Job A.J., Sikking, Maurits, Stroeks, Sophie, Gerretsen, Suzanne, Hazebroek, Mark R., Knackstedt, Christian, Nijveldt, Robin, and Heymans, Stephane R.B.
- JACC.Cardiovascular imaging. 16(7):991-992
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Jenewein, Erin C., Cotter, Susan, Roberts, Tawna, Kulp, Marjean, Mitchell, G. Lynn, Jones-Jordan, Lisa A., Chen, Angela M., Hopkins, Kristine, Huang, Kristine, Amster, Deborah, Fecho, Gregory, Tyler, Julie, Meiyeppen, Shivakhaami, Scheiman, Mitchell, Scheiman, Mitchell, Cooper, Jeffrey, Schulman, Erica, Hamian, Kimberly, Iacono, Danielle, Larson, Steven, Leung, Valerie, Meeder, Sara, Ramos, Elaine, Ritter, Steven, Steiner, Audra, Stormann, Alexandria, Vricella, Marilyn, Zhu, Xiaoying, Tamkins, Susanna, Aguilera, Naomi, Brafman, Elliot, Capo, Hilda, Cavuoto, Kara, Crespo, Isaura, Dowling, Monica, Draskovic, Kristie, Farag, Miriam, Fischer, Vicky, Grace, Sara, Gutierrez, Ailen, Manchola-Orozco, Carolina, Martinez, Maria, McKeown, Craig, Osigian, Carla, Pham, Tuyet-Suong, Small, Leslie, Townsend, Natalie, Gallaway, Michael, Boas, Mark, Calvert, Christine, Franz, Tara, Gerrouge, Amanda, Hayden, Donna, Margolies, Zachary, Myung, Jenny, Pollack, Karen, Shoge, Ruth, Tang, Andrew, Tannen, Noah, Trieu, Lynn, Trujillo, Luis, Buckland, Michelle, Ellis, Allison, Fogt, Jennifer, McDaniel, Catherine, McGann, Taylor, Morrison, Ann, Mulvihill, Shane, Peiffer, Adam, Plaumann, Maureen, Pierce, Gil, Preston, Julie, Reuter, Kathleen, Stevens, Nancy, Teeny, Jake, Toole, Andrew, Widmer, Douglas, Zimmerman, Aaron, Barnhardt, Carmen, Borsting, Eric, Chu, Raymond, Parker, Susan, Retnasothie, Dashaini, Wu, Judith, Hertle, Richard, Clark, Penny, Culp, Kelly, Fraley, Kathy, Grant, Drusilla, Hanna, Nancy, Knox, Stephanie, Lawhon, William, Li, Lan, Mitcheff, Sarah, Ricker, Isabel, Solis, Casandra, Wall, Palak, Zaczyk, Samantha, Marsh-Tootle, Wendy, Bowen, Michelle, Call, Terri, Domnanovich, Kristy, Frazier, Marcela, Guyette, Nicole, Hayes, Oakley, Houser, John, Lee, Sarah, Montejo, Jenifer, Oechslin, Tamara, Turner, Candace, Weise, Katherine, Coulter, Rachel, Bade, Annette, Bansal, Surbhi, Falco, Laura, Green, Katherine, Irizarry, Gabriela, Jhajj, Jasleen, Patterson, Nicole, Rodena, Jacqueline, Tea, Yin, Weiss, Dana, Zakaib, Lauren, Lorenzana, Ingryd, Meza, Yesena, Mann, Ryan, Quezada, Mariana, Rein, Scott, Rudaitis, Indre, Stepleton, Susan, Wajs, Beata, Redford, Maryann, Hertle, Richard, Redford, Maryann, Denton, Carolyn, Arnold, Eugene, Borsting, Eric, Chase, Christopher, Denton, Carolyn, Wee, Sharyl, Dahl-Leonard, Katlynn, Powers, Kenneth, Alaniz, Amber, Diener-West, Marie, Good, William V., Grisham, David, Kratochvil, Christopher J., Revicki, Dennis, Wanzek, Jeanne, Pollack, Karen, Abraham, Mustafa, Dangelo, Julianne, Hegedus, Jordan, Jones, Ian, Junglas, Alexander, Lee, Jihyun, Nettles, Jadin, Mitchell, Curtis, Osman, Mawada, Scott-Tibbs, Gloria, Sinnott, Loraine, Teasley, Chloe, Vang, Victor, and Varghese, Robin
- Ophthalmic and Physiological Optics. January, 2023, Vol. 43 Issue 1, p105, 11 p.
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Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Nardone GG, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Liang J, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Mercader JM, Costanzo MC, Jang D, Burtt NP, Villalpando CG, Orozco L, Fornage M, Tai E, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Qu J, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, Hart LM', Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Chuang LM, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, Willemsen AHM, Cupples L, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen Y, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson PWF, Frayling TM, Hirschhorn JN, Kathiresan S, Mohlke KL, Sun YV, Morris AP, Boehnke M, Brown CD, Natarajan P, Deloukas P, Willer CJ, Assimes TL, and Peloso GM
Genome biology [Genome Biol] 2022 Dec 27; Vol. 23 (1), pp. 268. Date of Electronic Publication: 2022 Dec 27.
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Humans, Sex Characteristics, Phenotype, Lipids genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Genome-Wide Association Study, and Genetic Predisposition to Disease
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Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.
Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
(© 2022. The Author(s).)
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Vos JL, Leiner T, van Dijk APJ, Pedrizzetti G, Alenezi F, Rodwell L, van der Wegen CTPM, Post MC, Driessen MMP, and Nijveldt R
European heart journal. Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2022 Dec 19; Vol. 24 (1), pp. 78-87.
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Humans, Ventricular Pressure, Cross-Sectional Studies, Heart Ventricles, Ventricular Function, Left, Stroke Volume, Magnetic Resonance Spectroscopy, Hypertension, Pulmonary, and Ventricular Dysfunction, Left
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Aims: Precapillary pulmonary hypertension (pPH) affects left ventricular (LV) function by ventricular interdependence. Since LV ejection fraction (EF) is commonly preserved, LV dysfunction should be assessed with more sensitive techniques. Left atrial (LA) strain and estimation of LV intraventricular pressure gradients (IVPG) may be valuable in detecting subtle changes in LV mechanics; however, the value of these techniques in pPH is unknown. Therefore, the aim of our study is to evaluate LA strain and LV-IVPGs from cardiovascular magnetic resonance (CMR) cines in pPH patients.
Methods and Results: In this cross-sectional study, 31 pPH patients and 22 healthy volunteers underwent CMR imaging. Feature-tracking LA strain was measured on four- and two-chamber cines. LV-IVPGs (from apex-base) are computed from a formulation using the myocardial movement and velocity of the reconstructed 3D-LV (derived from long-axis cines using feature-tracking). Systolic function, both LV EF and systolic ejection IVPG, was preserved in pPH patients. Compared to healthy volunteers, diastolic function was impaired in pPH patients, depicted by (i) lower LA reservoir (36 ± 7% vs. 26 ± 9%, P < 0.001) and conduit strain (26 ± 6% vs. 15 ± 8%, P < 0.001) and (ii) impaired diastolic suction (-9.1 ± 3.0 vs. ‒6.4 ± 4.4, P = 0.02) and E-wave decelerative IVPG (8.9 ± 2.6 vs. 5.7 ± 3.1, P < 0.001). Additionally, 11 pPH patients (35%) showed reversal of IVPG at systolic-diastolic transition compared to none of the healthy volunteers (P = 0.002).
Conclusions: pPH impacts LV function by altering diastolic function, demonstrated by an impairment of LA phasic function and LV-IVPG analysis. These parameters could therefore potentially be used as early markers for LV functional decline in pPH patients.
Competing Interests: Conflict of interest: none declared.
(© Crown copyright 2022.)
33. Circulating adipose tissue proteins involved in atrial fibrillation: An explorative scoping review. [2022]
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Meulendijks ER, Krul SPJ, Baalman SW, de Vries TAC, Wesselink R, Ernault AC, Kawasaki M, Al-Shama R, Neefs J, Limpens J, and de Groot JR
Trends in cardiovascular medicine [Trends Cardiovasc Med] 2022 Dec 17. Date of Electronic Publication: 2022 Dec 17.
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Obesity increases the risk of atrial fibrillation (AF), potentially through proteins secreted by adipose tissue (AT) that affect atrial electrical and structural remodeling. We aim to give a comprehensive overview of circulating AT proteins involved in inflammation and fibrosis, that are associated with prevalent AF (paroxysmal or persistent) and the risk on developing new-onset AF. These include adipokines, defined as proteins enriched in AT as adiponectin, but also proteins less specific to AT. We systematically performed an explorative search for studies reporting associations between proteins secreted from cells residing in the AT and AF, and additionally assessed the effect of obesity on these proteins by a secondary search. The AT proteins involved in inflammation were mostly increased in patients with prevalent and new-onset AF, and with obesity, while the AT enriched adipokines were mostly not associated with AF. This review provides insight into circulating adipose tissue proteins involved in AF substrate formation.
(Copyright © 2022. Published by Elsevier Inc.)
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Saunders GRB, Wang X, Chen F, Jang SK, Liu M, Wang C, Gao S, Jiang Y, Khunsriraksakul C, Otto JM, Addison C, Akiyama M, Albert CM, Aliev F, Alonso A, Arnett DK, Ashley-Koch AE, Ashrani AA, Barnes KC, Barr RG, Bartz TM, Becker DM, Bielak LF, Benjamin EJ, Bis JC, Bjornsdottir G, Blangero J, Bleecker ER, Boardman JD, Boerwinkle E, Boomsma DI, Boorgula MP, Bowden DW, Brody JA, Cade BE, Chasman DI, Chavan S, Chen YI, Chen Z, Cheng I, Cho MH, Choquet H, Cole JW, Cornelis MC, Cucca F, Curran JE, de Andrade M, Dick DM, Docherty AR, Duggirala R, Eaton CB, Ehringer MA, Esko T, Faul JD, Fernandes Silva L, Fiorillo E, Fornage M, Freedman BI, Gabrielsen ME, Garrett ME, Gharib SA, Gieger C, Gillespie N, Glahn DC, Gordon SD, Gu CC, Gu D, Gudbjartsson DF, Guo X, Haessler J, Hall ME, Haller T, Harris KM, He J, Herd P, Hewitt JK, Hickie I, Hidalgo B, Hokanson JE, Hopfer C, Hottenga J, Hou L, Huang H, Hung YJ, Hunter DJ, Hveem K, Hwang SJ, Hwu CM, Iacono W, Irvin MR, Jee YH, Johnson EO, Joo YY, Jorgenson E, Justice AE, Kamatani Y, Kaplan RC, Kaprio J, Kardia SLR, Keller MC, Kelly TN, Kooperberg C, Korhonen T, Kraft P, Krauter K, Kuusisto J, Laakso M, Lasky-Su J, Lee WJ, Lee JJ, Levy D, Li L, Li K, Li Y, Lin K, Lind PA, Liu C, Lloyd-Jones DM, Lutz SM, Ma J, Mägi R, Manichaikul A, Martin NG, Mathur R, Matoba N, McArdle PF, McGue M, McQueen MB, Medland SE, Metspalu A, Meyers DA, Millwood IY, Mitchell BD, Mohlke KL, Moll M, Montasser ME, Morrison AC, Mulas A, Nielsen JB, North KE, Oelsner EC, Okada Y, Orrù V, Palmer ND, Palviainen T, Pandit A, Park SL, Peters U, Peters A, Peyser PA, Polderman TJC, Rafaels N, Redline S, Reed RM, Reiner AP, Rice JP, Rich SS, Richmond NE, Roan C, Rotter JI, Rueschman MN, Runarsdottir V, Saccone NL, Schwartz DA, Shadyab AH, Shi J, Shringarpure SS, Sicinski K, Skogholt AH, Smith JA, Smith NL, Sotoodehnia N, Stallings MC, Stefansson H, Stefansson K, Stitzel JA, Sun X, Syed M, Tal-Singer R, Taylor AE, Taylor KD, Telen MJ, Thai KK, Tiwari H, Turman C, Tyrfingsson T, Wall TL, Walters RG, Weir DR, Weiss ST, White WB, Whitfield JB, Wiggins KL, Willemsen G, Willer CJ, Winsvold BS, Xu H, Yanek LR, Yin J, Young KL, Young KA, Yu B, Zhao W, Zhou W, Zöllner S, Zuccolo L, Batini C, Bergen AW, Bierut LJ, David SP, Gagliano Taliun SA, Hancock DB, Jiang B, Munafò MR, Thorgeirsson TE, Liu DJ, and Vrieze S
Nature [Nature] 2022 Dec; Vol. 612 (7941), pp. 720-724. Date of Electronic Publication: 2022 Dec 07.
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Humans, Genome-Wide Association Study methods, Risk Factors, Transcriptome, Sample Size, Genetic Loci genetics, Europe ethnology, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Multifactorial Inheritance genetics, Tobacco Use genetics, Alcohol Drinking genetics, and Internationality
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Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury 1-4 . These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries 5 . Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.
(© 2022. The Author(s).)
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35. Reply: Further Insights Into the Prognostic Value of Left Atrial Strain in Dilated Cardiomyopathy? [2022]
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Raafs AG, Henkens MTHM, Vos JL, Nijveldt R, and Verdonschot JAJ
JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2022 Dec; Vol. 15 (12), pp. 2156-2157.
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Humans, Prognosis, Predictive Value of Tests, Cardiomyopathy, Dilated diagnostic imaging, Atrial Fibrillation, and Atrial Appendage
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Makhlin I, McAndrew NP, Wileyto EP, Clark AS, Holmes R, Bottalico LN, Mesaros C, Blair IA, Jeschke GR, Fox KR, Domchek SM, Matro JM, Bradbury AR, Feldman MD, Hexner EO, Bromberg JF, and DeMichele A
NPJ breast cancer [NPJ Breast Cancer] 2022 Nov 11; Vol. 8 (1), pp. 122. Date of Electronic Publication: 2022 Nov 11.
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Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.
(© 2022. The Author(s).)
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Petrovic B, O'Brien MA, Liddy C, Afkham A, McGee SF, Morgan SC, Segal R, Bender JL, Sussman J, Urquhart R, Fitch M, Schneider ND, and Grunfeld E
Current oncology (Toronto, Ont.) [Curr Oncol] 2022 Nov 03; Vol. 29 (11), pp. 8401-8414. Date of Electronic Publication: 2022 Nov 03.
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Male, Humans, Qualitative Research, Communication, Internet, Health Personnel, and Neoplasms
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Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being consistently copied on patient reports. We evaluated an asynchronous web-based communication system ("eOncoNote") for primary care providers and cancer specialists to improve cancer care coordination. The objectives were to examine patients' perceptions of the role of eOncoNote in their healthcare, and HCPs' experiences of implementing eOncoNote. Qualitative interviews were conducted with patients with breast and prostate cancer, primary care providers, and cancer specialists. Eighteen patients and fourteen HCPs participated. Six themes were identified from the patient interviews focusing on HCP and patient roles related to care coordination and patient awareness of communication among their HCPs. Four themes were identified from HCP interviews related to the context of care coordination and experience with eOncoNote. Both patients and HCPs described the important role patients and caregivers play in care coordination. The results show that patients were often unaware of the communication between their HCPs and assumed they were communicating. HCPs encountered challenges incorporating eOncoNote into their workflow.
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Vaughn J, Cunningham R, Schroeder LH, Waddill C, Peterson MJ, Gambacorta MR, and Sims S
Nursing forum [Nurs Forum] 2022 Nov; Vol. 57 (6), pp. 1373-1380. Date of Electronic Publication: 2022 Oct 29.
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Humans, Interprofessional Relations, Interprofessional Education, Learning, Attitude of Health Personnel, Patient Care Team, Students, Nursing, and Sports
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Background: The purpose of this article is to describe the development, implementation, and evaluation of a Simulation Interprofessional Education (Sim-IPE) activity for healthcare students from different disciplines (athletic training [AT] and nursing). The objective for the Sim-IPE activity was to engage AT and prelicensure nursing students in a realistic healthcare scenario to enhance knowledge about one another's profession, develop interprofessional skills, collaborate with one another, and communicate effectively as a team as they performed care.
Methods: This mixed methods study employed a one-time posttest design for a convenience sample of AT and prelicensure nursing students following a simulation intervention. Students completed the Student Perceptions of Interprofessional Clinical Education-Revised (SPICE-R) survey and answered open-ended response questions.
Results: Thirteen students (N = 13) from Cohort 1 and 12 students (N = 12) from Cohort 2 completed the SPICE-R survey. Most students strongly agreed/agreed for each of the SPICE-R survey questions. Qualitative findings indicated the students positively perceived the Sim-IPE activity as it helped them discover the value of interprofessional patient care.
Discussion: The quantitative findings indicated that the students found the Sim-IPE an effective learning methodology to achieve the objectives while the qualitative findings gave further insight into the students' perceptions of interprofessional teamwork and the value of the prebrief session conducted before the simulation. The findings will inform future Sim-IPE activities involving additional groups of healthcare students.
(© 2022 The Authors. Nursing Forum published by Wiley Periodicals LLC.)
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39. Antibody response to a third dose of SARS-CoV-2 vaccine in heart and lung transplant recipients. [2022]
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Alejo JL, Ruck JM, Chiang TPY, Abedon AT, Kim JD, Avery RK, Tobian AAR, Warren DS, Levan ML, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
Clinical transplantation [Clin Transplant] 2022 Nov; Vol. 36 (11), pp. e14818. Date of Electronic Publication: 2022 Sep 19.
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Humans, COVID-19 Vaccines, Antibody Formation, SARS-CoV-2, Transplant Recipients, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention control, and Lung Transplantation
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Cooper, Alannah L., Mazzer, Jacqueline, Martin-Robins, Dipna, and Brown, Janie A.
- Journal of Clinical Nursing. November, 2022, Vol. 31 Issue 21-22, p3144, 11 p.
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41. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers. [2022]
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Hakkaart C, Pearson JF, Marquart L, Dennis J, Wiggins GAR, Barnes DR, Robinson BA, Mace PD, Aittomäki K, Andrulis IL, Arun BK, Azzollini J, Balmaña J, Barkardottir RB, Belhadj S, Berger L, Blok MJ, Boonen SE, Borde J, Bradbury AR, Brunet J, Buys SS, Caligo MA, Campbell I, Chung WK, Claes KBM, Collonge-Rame MA, Cook J, Cosgrove C, Couch FJ, Daly MB, Dandiker S, Davidson R, de la Hoya M, de Putter R, Delnatte C, Dhawan M, Diez O, Ding YC, Domchek SM, Donaldson A, Eason J, Easton DF, Ehrencrona H, Engel C, Evans DG, Faust U, Feliubadaló L, Fostira F, Friedman E, Frone M, Frost D, Garber J, Gayther SA, Gehrig A, Gesta P, Godwin AK, Goldgar DE, Greene MH, Hahnen E, Hake CR, Hamann U, Hansen TVO, Hauke J, Hentschel J, Herold N, Honisch E, Hulick PJ, Imyanitov EN, Isaacs C, Izatt L, Izquierdo A, Jakubowska A, James PA, Janavicius R, John EM, Joseph V, Karlan BY, Kemp Z, Kirk J, Konstantopoulou I, Koudijs M, Kwong A, Laitman Y, Lalloo F, Lasset C, Lautrup C, Lazaro C, Legrand C, Leslie G, Lesueur F, Mai PL, Manoukian S, Mari V, Martens JWM, McGuffog L, Mebirouk N, Meindl A, Miller A, Montagna M, Moserle L, Mouret-Fourme E, Musgrave H, Nambot S, Nathanson KL, Neuhausen SL, Nevanlinna H, Yie JNY, Nguyen-Dumont T, Nikitina-Zake L, Offit K, Olah E, Olopade OI, Osorio A, Ott CE, Park SK, Parsons MT, Pedersen IS, Peixoto A, Perez-Segura P, Peterlongo P, Pocza T, Radice P, Ramser J, Rantala J, Rodriguez GC, Rønlund K, Rosenberg EH, Rossing M, Schmutzler RK, Shah PD, Sharif S, Sharma P, Side LE, Simard J, Singer CF, Snape K, Steinemann D, Stoppa-Lyonnet D, Sutter C, Tan YY, Teixeira MR, Teo SH, Thomassen M, Thull DL, Tischkowitz M, Toland AE, Trainer AH, Tripathi V, Tung N, van Engelen K, van Rensburg EJ, Vega A, Viel A, Walker L, Weitzel JN, Wevers MR, Chenevix-Trench G, Spurdle AB, Antoniou AC, and Walker LC
Communications biology [Commun Biol] 2022 Oct 06; Vol. 5 (1), pp. 1061. Date of Electronic Publication: 2022 Oct 06.
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BRCA1 Protein genetics, BRCA2 Protein genetics, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Heterozygote, Humans, RNA, Messenger, Breast Neoplasms genetics, and Breast Neoplasms pathology
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The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
(© 2022. The Author(s).)
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Vos JL, Raafs AG, van der Velde N, Germans T, Biesbroek PS, Roes K, Hirsch A, Heymans SRB, and Nijveldt R
Journal of the American Heart Association [J Am Heart Assoc] 2022 Oct 04; Vol. 11 (19), pp. e025106. Date of Electronic Publication: 2022 Sep 21.
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Arrhythmias, Cardiac, Contrast Media, Female, Gadolinium, Heart Atria, Humans, Magnetic Resonance Imaging, Cine methods, Magnetic Resonance Spectroscopy, Male, Predictive Value of Tests, Prognosis, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Heart Failure, and Myocarditis diagnostic imaging
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Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P =0.02; LV-global circumferential strain: HR 1.15, P =0.02; LV-global radial strain: HR 0.98, P =0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance.
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Alejo JL, Mitchell J, Chiang TP, Chang A, Abedon AT, Werbel WA, Boyarsky BJ, Zeiser LB, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Moore LW, Guha A, Huang HJ, Knight RJ, Gaber AO, Ghobrial RM, Garonzik-Wang JM, Segev DL, and Bae S
Transplantation [Transplantation] 2022 Oct 01; Vol. 106 (10), pp. e452-e460. Date of Electronic Publication: 2022 Jul 21.
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Antibodies, Viral, Antibody Formation, BNT162 Vaccine, Humans, Immunosuppressive Agents adverse effects, Machine Learning, Mycophenolic Acid, SARS-CoV-2, Vaccines, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention control, COVID-19 Vaccines adverse effects, and Transplant Recipients
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Background: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.
Methods: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital.
Results: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ .
Conclusions: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. M.L.L. is the Social Media Editor for Transplantation and is a consultant for Takeda/Shire and Patients Like Me. The other authors declare no conflicts of interest.
(Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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Chang A, Strauss AT, Alejo JL, Chiang TP, Hernandez NF, Zeiser LB, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Werbel WA, and Segev DL
Hepatology communications [Hepatol Commun] 2022 Oct; Vol. 6 (10), pp. 2990-2992. Date of Electronic Publication: 2022 Jul 05.
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Antibodies, Humans, Kinetics, RNA, Messenger, SARS-CoV-2 genetics, Vaccination, COVID-19 prevention control, and Liver Transplantation
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Link-Gelles, Ruth, Lutterloh, Emily, Ruppert, Patricia Schnabel, Backenson, P. Bryon, St. George, Kirsten, Rosenberg, Eli S., Anderson, Bridget J., Fuschino, Meghan, Popowich, Michael, Punjabi, Chitra, Souto, Maria, McKay, Kevin, Rulli, Samuel, Insaf, Tabassum, Hill, Dustin, Kumar, Jessica, Gelman, Irina, Jorba, Jaume, Ng, Terry Fei Fan, Gerloff, Nancy, Masters, Nina B., Lopez, Adriana, Dooling, Kathleen, Stokley, Shannon, Kidd, Sarah, Oberste, M. Steven, Routh, Janell, Routh, Janell, Belgasmi, Hanen, Brister, Barrett, Bullows, James E., Burns, Cara C., Castro, Christina J., Cory, Janine, Dybdahl-Sissoko, Naomi, Emery, Brian D., English, Randall, Frolov, Ann D., Getachew, Halle, Henderson, Elizabeth, Hess, Alexandra, Mason, Karen, Mercante, Jeffrey W., Miles, Stacey Jeffries, Liu, Hongmei, Marine, Rachel L., Momin, Nehalraza, Pang, Hong, Perry, Daniel, Rogers, Shannon L., Short, Brandon, Sun, Hong, Tobolowsky, Farrell, Yee, Eileen, Hughes, Scott, Hygiene, Mental, Omoregie, Enoma, Hygiene, Mental, Rosen, Jennifer B., Hygiene, Mental, Zucker, Jane R., Hygiene, Mental, Alazawi, Mohammed, Bauer, Ursula, Godinez, Alex, Hanson, Brianna, Heslin, Eugene, McDonald, James, Mita-Mendoza, Neida K., Meldrum, Megan, Neigel, Dana, Suitor, Robin, Larsen, David A., Egan, Christina, Faraci, Nicola, Feumba, G. Stephanie, Gray, Todd, Lamson, Daryl, Laplante, Jennifer, McDonough, Kathleen, Migliore, Natalie, Moghe, Amruta, Ogbamikael, Simon, Plitnick, Jonathan, Ramani, Rama, Rickerman, Lindsey, Rist, Erik, Schoultz, Lynsey, Shudt, Matthew, Krauchuk, Julie, Medina, Eric, Lawler, Jacqueline, Boss, Heather, Barca, Emanuele, Ghazali, Dabish B., Goyal, Tarini, Marinelli, Sean J.P., Roberts, Jackson A., Russo, Grace B., Thakur, Kiran T., and Yang, Vivian Q.
- American Journal of Transplantation. October, 2022, Vol. 22 Issue 10, p2470, 5 p.
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Weedon MN, Jones SE, Lane JM, Lee J, Ollila HM, Dawes A, Tyrrell J, Beaumont RN, Partonen T, Merikanto I, Rich SS, Rotter JI, Frayling TM, Rutter MK, Redline S, Sofer T, Saxena R, and Wood AR
PLoS genetics [PLoS Genet] 2022 Sep 22; Vol. 18 (9), pp. e1010356. Date of Electronic Publication: 2022 Sep 22 (Print Publication: 2022).
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Humans, Phenotype, Receptors, G-Protein-Coupled genetics, Sleep genetics, Circadian Rhythm genetics, and Sleep Wake Disorders genetics
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Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.
Competing Interests: The authors have declared that no competing interests exist.
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Bowden J, Harrison NJ, Caruso J, Room R, Pettigrew S, Olver I, and Miller C
BMC public health [BMC Public Health] 2022 Sep 19; Vol. 22 (1), pp. 1775. Date of Electronic Publication: 2022 Sep 19.
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Adult, Australia epidemiology, Female, Humans, Male, Risk Factors, Surveys and Questionnaires, Alcohol Drinking epidemiology, and Diet
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Background: Alcohol is a discretionary, energy dense, dietary component. Compared to non-drinkers, people who consume alcohol report higher total energy intake and may be at increased risk of weight gain, overweight, and obesity, which are key preventable risk factors for illness. However, accurate consumer knowledge of the energy content in alcohol is low. To inform future behaviour change interventions among drinkers, this study investigated individual characteristics associated with changing alcohol consumption due to energy-related concerns.
Methods: An online survey was undertaken with 801 Australian adult drinkers (18-59 years, 50.2% female), i.e. who consumed alcohol at least monthly. In addition to demographic and health-related characteristics, participants reported past-year alcohol consumption, past-year reductions in alcohol consumption, frequency of harm minimisation strategy use (when consuming alcohol), and frequency of changing alcohol consumption behaviours because of energy-related concerns.
Results: When prompted, 62.5% of participants reported changing alcohol consumption for energy-related reasons at least 'sometimes'. Women, those aged 30-44 years, metropolitan residents, those with household income $80,001-120,000, and risky/more frequent drinkers had increased odds of changing consumption because of energy-related concerns, and unemployed respondents had reduced odds.
Conclusions: Results indicate that some sociodemographic groups are changing alcohol consumption for energy-related reasons, but others are not, representing an underutilised opportunity for health promotion communication. Further research should investigate whether messaging to increase awareness of alcohol energy content, including through systems-based policy actions such as nutritional/energy product labelling, would motivate reduced consumption across a broader range of drinkers.
(© 2022. The Author(s).)
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Alejo JL, Chiang TPY, Bowles Zeiser L, Kim JD, Mitchell J, Avery RK, Tobian AAR, Abedon RR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
Transplantation [Transplantation] 2022 Sep 01; Vol. 106 (9), pp. e413-e415. Date of Electronic Publication: 2022 Jun 03.
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Humans, Incidence, Transplant Recipients, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation adverse effects
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Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. is an associate editor of Transplantation and has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. M.L.L. is a Social Media Editor for Transplantation and receives consulting honoraria that are not related to her authorship of the article from Takeda/Patients Like Me. The other authors declare no conflicts of interest.
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Chang A, Mitchell J, Alejo JL, Chiang TPY, Abedon AT, Kim JD, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
Clinical transplantation [Clin Transplant] 2022 Sep; Vol. 36 (9), pp. e14772. Date of Electronic Publication: 2022 Jul 19.
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Ad26COVS1, Antibodies, Viral, COVID-19 Vaccines, Humans, RNA, Messenger, SARS-CoV-2 genetics, Transplant Recipients, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation adverse effects
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Chiang TP, Alejo JL, Mitchell J, Kim JD, Abedon AT, Karaba AH, Thomas L, Levan ML, Garonzik-Wang JM, Avery RK, Pekosz A, Clarke WA, Warren DS, Tobian AAR, Massie AB, Segev DL, and Werbel WA
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Sep; Vol. 22 (9), pp. 2254-2260. Date of Electronic Publication: 2022 May 03.
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Antibodies, Viral, COVID-19 Vaccines adverse effects, Humans, RNA, Messenger genetics, SARS-CoV-2, Transplant Recipients, Vaccination, 2019-nCoV Vaccine mRNA-1273 adverse effects, BNT162 Vaccine adverse effects, COVID-19 epidemiology, COVID-19 prevention control, Influenza Vaccines, and Organ Transplantation adverse effects
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Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR = 1.10 1.40 1.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR = 0.44 0.92 1.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.41 1.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR = 1.38 2.63 5.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.
(© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
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