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Guidelines endorse coronary artery bypass as the preferred revascularization strategy for patients with left main and/or multivessel coronary artery disease (CAD). However, many patients are deemed excessively high risk for surgery after Heart Team evaluation. No prospective studies have examined contemporary treatment patterns, rationale for surgical decision-making, completeness of revascularization with percutaneous coronary intervention (PCI), and outcomes in this high-risk population with advanced CAD.We designed the Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients with Multivessel or Left Main Coronary Artery Disease (OPTIMUM) registry, a prospective, multicenter study of patients with "surgical anatomy" determined to be at prohibitive risk for bypass surgery. The primary outcome is comparison of observed to predicted 30-day mortality, with secondary outcomes of patient-reported health status and the association between completeness of revascularization and clinical outcomes. Patient characteristics driving surgical risk determinations will be reported, and peri-operative risk will be assessed using validated scoring methods. Angiograms will be assessed by an independent core laboratory, and clinical events will be adjudicated.Clinical outcomes assessments will include 30-day and 1-year cardiovascular events, health status at 1, 6 and 12-months, and 5-year mortality.OPTIMUM is the first prospective, multicenter study to examine treatment strategies and outcomes among multivessel CAD patients deemed ineligible for surgical revascularization after Heart Team assessment. This registry will provide unique insights into the clinical decision-making, revascularization practices, safety, effectiveness, and health status outcomes in this high-risk population.

Background The EXCEL trial reported similar five-year rates of the primary composite outcome of death, myocardial infarction (MI), or stroke after percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) for treatment of obstructive left main coronary artery disease (LMCAD). Aims We sought to determine whether these outcomes remained consistent regardless of geography of enrolment. Methods We performed a pre-specified subgroup analysis based on regional enrolment. Results Among 1,905 patients randomised to PCI (n=948) or CABG (n=957), 1,075 (56.4%) were recruited at 52 European Union (EU) centres, and 752 (39.5%) were recruited at 67 North American (NA) centres. EU versus NA patients varied according to numerous baseline demographics, anatomy, pharmacotherapy and procedural characteristics. Nonetheless, the relative rates of the primary endpoint after PCI versus CABG were consistent across EU versus NA centres at 30 days and 5 years. However, NA participants had substantially higher late rates of ischaemia-driven revascularisation (IDR) after PCI, driven predominantly by the need for greater target vessel and lesion revascularisation. This culminated in a significant difference in the relative risk of the secondary composite outcome of death, MI, stroke, or IDR at 5 years (pinteraction=0.02). Conclusions In the EXCEL trial, the relative risks for the 30-day and five-year primary composite outcome of death, MI or stroke after PCI versus CABG were consistent irrespective of geography. However, five-year rates of IDR after PCI were significantly higher in NA centres, a finding the Heart Team and patients should consider when making treatment decisions. ClinicalTrials.gov identifier: NCT01205776.

Funder: Akademiska Sjukhuset; doi: http://dx.doi.org/10.13039/501100005423, Funder: Uppsala University, PURPOSE: [11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers. METHODS: Fifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis. RESULTS: Uptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65-70, and SUV120 were 25, 22, and 17%. CONCLUSIONS: High adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083.

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease which involves multiple body systems (e.g., immune, nervous, digestive, circulatory) and research domains (e.g., immunology, metabolomics, the gut microbiome, genomics, neurology). Despite several decades of research, there are no established ME/CFS biomarkers available to diagnose and treat ME/CFS. Sharing data and integrating findings across these domains is essential to advance understanding of this complex disease by revealing diagnostic biomarkers and facilitating discovery of novel effective therapies. Methods The National Institutes of Health funded the development of a data sharing portal to support collaborative efforts among an initial group of three funded research centers. This was subsequently expanded to include the global ME/CFS research community. Using the open-source comprehensive knowledge archive network (CKAN) framework as the base, the ME/CFS Data Management and Coordinating Center developed an online portal with metadata collection, smart search capabilities, and domain-agnostic data integration to support data findability and reusability while reducing the barriers to sustainable data sharing. Results We designed the mapMECFS data portal to facilitate data sharing and integration by allowing ME/CFS researchers to browse, share, compare, and download molecular datasets from within one data repository. At the time of publication, mapMECFS contains data curated from public data repositories, peer-reviewed publications, and current ME/CFS Research Network members. Conclusions mapMECFS is a disease-specific data portal to improve data sharing and collaboration among ME/CFS researchers around the world. mapMECFS is accessible to the broader research community with registration. Further development is ongoing to include novel systems biology and data integration methods.

Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77).In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.UK National Institute for Health and Care Research.

Background: There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial. Methods: EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time. Results: Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56-1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32-3.67) (Pinteraction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (Pinteraction = 0.03), ischemia-driven revascularization (Pinteraction = 0.03), target vessel revascularization (Pinteraction = 0.007) and target vessel failure (Pinteraction = 0.0009). Conclusion: In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.

[Fifteen patients underwent [Uptake of [High adrenal uptake combined with a low unspecific liver uptake suggests thatClinicalTrials.gov , NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083.

Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P − 8) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10− 73) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10− 33) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10− 22). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines.

Background Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021. Methods Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds. Results In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%). Conclusions The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma (APA) is a common, curable cause of hypertension, but invasive methods of diagnosis and treatment contribute to -17%, the pre-specified margin of non-inferiority. The best univariate predictors of complete clinical cure were home systolic blood pressure (SBP)

BackgroundInformation is needed to monitor progress toward a level of population immunity to SARS-CoV-2 sufficient to disrupt viral transmission. We estimated the percentage of the United States (US) population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021.MethodsPublicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention (CDC) were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates to a range of population immunity thresholds.ResultsPresumed population immunity varied among states (43.1% to 70.6%), with 19 states with 60% or less of their population having been infected or vaccinated. Four states have presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (78% or higher).ConclusionsThe US remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.SummaryAs of August 26, 2021, no state has reached a population level of immunity thought to be sufficient to disrupt transmission. (78% or higher), with some states having remarkably low presumed immunity.

Gestational diabetes mellitus is a condition similar to type 2 diabetes mellitus (T2DM) in that patients are unable to compensate for the degree of insulin resistance, and both conditions are often treated with metformin. The comparative pharmacodynamic response to metformin in these 2 populations has not been studied. This study characterized insulin sensitivity, β-cell responsivity, and disposition index following a mixed-meal tolerance test utilizing a minimal model of glucose, insulin, and C-peptide kinetics before and during treatment with metformin. The study included women with gestational diabetes mellitus (n = 34), T2DM (n = 14), and healthy pregnant women (n = 30). Before treatment, the gestational diabetes mellitus group had significantly higher baseline (45%), dynamic (68%), static (71%), and total β-cell responsivity (71%) than the T2DM group. Metformin significantly increased insulin sensitivity (51%) as well as disposition index (97%) and decreased mixed-meal tolerance test peak glucose concentrations (8%) in women with gestational diabetes mellitus after adjustment for gestational age-dependent effects; however, in women with T2DM metformin only significantly affected peak glucose concentrations (22%) and had no significant effect on any other parameters. Metformin had a greater effect on the change in disposition index (Δ disposition index) in women with gestational diabetes mellitus than in those with T2DM (P = .01). In conclusion, response to metformin in women with gestational diabetes mellitus is significantly different from that in women with T2DM, which is likely related to the differences in disease severity.

BACKGROUND After 3 years of continuous-flow left ventricular assist device (CF-LVAD) support, nearly a third of patients develop at least moderate aortic insufficiency (AI). Percutaneous occluder devices, surgical aortic valve replacement (SAVR), and urgent heart transplantation are available treatment options. Transcatheter aortic valve replacement (TAVR) has not been widely used for treating symptomatic AI in patients on LVAD support. METHODS Retrospective chart review and data analysis from October 2010 through August 2017 was performed. A total of 286 patients with end-stage heart failure (ESHF) were implanted with a durable CF-LVAD. Nine patients subsequently developed significant symptomatic AI, which was treated with TAVR. RESULTS All 9 patients had 1 TAVR procedure with resolution of AI and were discharged home. Procedural complications include valve migration warranting a second valve for stabilization, retroperitoneal and groin hematoma, and pseudoaneurysm requiring thrombin injection. A significant improvement of the New York Heart Association classification was noted from the time of implant to 6 months. Two patients had unplanned heart failure‒related hospitalizations within 6 months. At 6 months, 89% of patients were alive on LVAD support. CONCLUSIONS TAVR is a successful treatment modality for LVAD patients who develop symptomatic AI.

The prognostic impact of high-sensitivity C-reactive protein (CRP) levels in patients with left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is unknown. We sought to determine the effect of elevated baseline CRP levels on the 3-year outcomes after LMCAD revascularization and to examine whether CRP influenced the relative outcomes of PCI versus CABG.In the EXCEL trial, patients with LMCAD and Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores ≤32 were randomized to PCI versus CABG. The primary composite outcome of death, myocardial infarction (MI), or stroke was analyzed according to baseline CRP levels.Among 999 patients with available CRP levels, median CRP was 3.10 mg/L (interquartile range 1.12-6.40 mg/L). The rate of the primary composite end point of death, MI, or stroke at 3 years steadily increased with greater baseline CRP levels. The adjusted relationship between the 3-year composite rate of death, MI, or stroke and baseline CRP modeled as a continuous log-transformed variable demonstrated steadily increasing event rates with greater CRP levels (adjusted hazard ratio, 1.26, 95% CI 1.10-1.44, P = .0008). Similarly, patients with CRP ≥10 mg/L had a 3-fold higher risk of the 3-year primary end point compared to patients with lower CRP levels (adjusted hazard ratio 2.92, 95% CI 1.88-4.54, P.0001). The association between an elevated CRP level and the adjusted 3-year risk of the primary composite end point did not differ according to revascularization strategy (PIn patients with LMCAD undergoing revascularization, elevated baseline CRP levels were strongly associated with subsequent death, MI, and stroke at 3 years, irrespective of the mode of revascularization. Further studies are warranted to determine whether anti-inflammatory therapies may improve the prognosis of high-risk patients with LMCAD following revascularization.

Objectives The study objectives were to evaluate the safety, efficacy, and hemodynamic performance of a novel stented bovine pericardial aortic valve bioprosthesis 2 years after implantation. Methods The PERIcardial SurGical AOrtic Valve ReplacemeNT Pivotal Trial enrolled patients with symptomatic moderate/severe aortic stenosis or regurgitation at centers in Canada, Europe, and the United States. We report the outcomes and hemodynamic performance in patients with up to 2 years of follow-up. Results A total of 1273 patients were enrolled, and 1110 underwent implantation. Among patients undergoing implantation, the mean age was 70.2 ± 8.9 years; 833 (75.0%) were male. Risk of mortality (Society of Thoracic Surgeons) was 2.0% ± 1.4%. At the time of analysis, 604 patients had completed the 2-year follow-up visit. Linearized late event rates were as follows: all death, 2.68%; valve-related death, 0.42%; valve thrombosis, 0.05%; endocarditis, 0.94%; thromboembolism, 1.68%; all hemorrhage, 2.94%; major hemorrhage, 1.99%; all paravalvular leak, 0.26%; and major paravalvular leak, 0.05% per patient-year. Mean 2-year aortic gradient and effective orifice area were 13.4 ± 5.0 mm Hg and 1.5 ± 0.37 cm2, respectively. Moderate and severe prosthesis–patient mismatch were observed in 43.5% and 34.8% of patients at 2 years, respectively. Improvement in New York Heart Association class compared with baseline was observed in 73.0% with moderate mismatch and 74.1% with severe mismatch. Conclusions The Avalus (Medtronic, Minneapolis, Minn) bovine pericardial valve demonstrates good clinical and safety outcomes at 2 years. Hemodynamic performance shows mean gradients comparable to currently available bovine pericardial aortic valves. There was no clinical impact of moderate to severe mismatch at 2 years. Further follow-up is required to evaluate midterm to long-term clinical outcome.

Varying definitions of procedural myocardial infarction (PMI) are in widespread use.This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.The pre-specified protocol definition of PMI (PMIPMIThe rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMI

Joseph Smith and his Latter-day Saints are caught out of time; they are much like living fossils. Their religious tradition is at once ancient and profoundly modern. While the movement arrived in the nineteenth century, it situated itself in the ancient past and the millennial future. Smith mediated between those times with scriptural translations best understood as targums—oral expansions, revisions, and interpretations that achieve the status of scripture—of the Bible, especially the first eleven chapters of Genesis and their primeval history. These targums reconfigure the Bible and create the possibility of a biblical world occupied by the Latter-day Saints. Smith’s targums and his metaphysics of translation were together concerned with escape routes from three modern prisons: mortal language, flattened time, and individualism.

Among many remarkable claims, Mormon founder Joseph Smith reported that he had translated ancient scriptures. He dictated the Book of Mormon, an American Bible from metal plates associated with Native antiquity; directly rewrote the King James Bible; and produced a scripture, derived from Egyptian funerary papyri, that he called the Book of Abraham. Smith and his followers used the term “translation” to describe the genesis of these English texts, which remain canonical for the Church of Jesus Christ of Latter-day Saints. Most commenters see these scriptures as merely linguistic objects; the central and controversial question has been whether Smith’s English texts are literal translations of extant source documents. On closer inspection, though, his translations are far more metaphysical than linguistic. These translations express a nonordinary power of language to connect people across barriers of space and time. Within these metaphysical scriptures, Smith expounded a theology of human deification that he also termed “translation.” This one word thus referred to a scripture capable of mediating between the living and the dead and to the transformation of humans into divine beings. Joseph Smith’s projects of metaphysical translation place Mormonism at a productive edge of tense transitions later associated with secular modernity, a modernity challenged by the very existence of the Latter-day Saints. Smith’s translations and the theology that supported them illuminate the power and vulnerability of his critique of American culture in transition as they set the stage for two more centuries of cultural change.

Smith culminated his metaphysics of translation in the rites of the Nauvoo temple in the early 1840s. The temple rites were a striking combination of Smith’s targums, the Hebrew and Christian Bibles, Freemasonry, ancient mystery religions, and his sense about the connections of humans and texts. This liturgy was Smith’s final rereading of the Hebrew Bible’s primeval history, and it pulled his followers to Eden and thence to heaven as transformed, divine beings. These rites were an apotheosis not just of Smith’s followers but also of his metaphysics of translation. In the temple, Smith worked to define space and time in terms of human beings. In an echo of Hebrew genealogies, Smith measured time in parental bonds effected by a force he called priesthood. These bonds at the base of time tied God to humanity and humans to each other.

Joseph Smith’s mode of thought expressed his avid interest in ideas, concepts, and possibilities that openly defied American norms and expectations. He was especially prone to reject dualisms (matter and spirit, immanent and transcendent, profane and sacred) in a way that merged complementary realms without using them up in the process. Early Latter-day Saint theology argued by its presence and its sensibilities that the cultural trade-offs and limitations that seem necessary to us on the other side of the twentieth century were not inevitable. There was no mandatory compromise between this-worldly flourishing and other-worldly happiness, between human agency and divine presence, between the mechanisms of human life and their eternal meanings.

Modern philosophical positions have restricted or eliminated the power and scope of the “language beyond language” once thought to have existed at the origins of the world. In this view, mortal language is the only language—either there is no primordial sacred language, or it exists but humans have no access to it. Joseph Smith saw these postures as capitulation to the curse of language at Babel (Genesis 11), which haunted him. The quest for pure language was a central aspect of his religious career and is a direct rejection of modernist assumptions about the potential of language. This quest for pure language—focused especially on the power of the hieroglyph—extended across Smith’s career, including extensive explorations of the Edenic language and traditions about powerful, nonordinary language.

Joseph Smith saw himself as a seer called to rescue the Bible from Protestantism. Smith’s first scripture, his Book of Mormon, repaired, expanded, and revised the Protestant Bible in order to tell America’s primeval history. This Mormon scripture pointed out and exploited the Bible’s weaknesses even as it relied on the infrastructure of that very Bible. The Book of Mormon demonstrated strength where the Bible showed weakness—access to original manuscripts, plain language, canonization, transmission, ecclesiastical direction, and translation itself. The Book of Mormon wasn’t ever intended to be an independent scripture, but instead to be integrated with the Bible it had transformed. Through the Book of Mormon, Smith translated the Bible from one world and vision of scripture to another, in a way that obliterated the temporal separation of the generations of human history. He became thereby a time traveler, with scripture as his time machine.

Joseph Smith and his early Mormon followers loved and embraced many Enlightenment ideas of selfhood—human agency, freedom of religious expression, and an extremely high anthropology. In this respect, they sound modern, even emphatically so. But they also saw modern individualism as an oppressive prison. They sought a mechanism to transform themselves into the best of both humans and gods. The mechanism by which they achieved these ontological changes was what Smith—following and modifying generations of Christian thought—called translation. He elaborated multiple avenues out of the prison of modern individualism, including sacred movement through space, even to a physical heaven, and establishment of otherworldly communitarian settlements based on the model of a primordial city called Zion and led by the mystical hero Enoch. The ways Latter-day Saints navigated the incipient tensions of church versus state reflected their position, standing askew to the usual positions of modern Western thought.

The Latter-day Saint Book of Abraham is an excellent test case for understanding Smith’s complementary modes of translation. Both insiders and outsiders have used a narrow linguistic model to understand Smith’s encounter with ancient Egyptian papyri he purchased in Ohio in 1835. But, according to the logic of early Mormon thought, the translation problems at hand were metaphysical as well as linguistic. The written texts of Smith’s Egyptian project were a subset of the spiritual gift of glossolalia, in this case graphic glossolalia. This spiritual gift generated an Egyptian Bible that became central to the Nauvoo temple liturgy, which served as the ritual infrastructure of Smith’s Chain of Belonging (his recasting of the traditional Chain of Being). The Egyptian Bible was thus an important example of the metaphysics of translation and the connective tissue between Smith’s early scriptures and the ultimate ritual system that merged humans and texts.

In the aftermath of the Book of Mormon, Smith and his disciples saw that the King James Bible itself needed to be more directly repaired, in a project they called the New Translation. The project encompassed three phases: (1) visionary work on the primeval history, (2) direct repair of the English text, and (3) marvelously literal exegeses that extended through Smith’s entire career. Contrary to prior treatments, this New Translation project also included large sections of the scripture called Doctrine and Covenants. This chapter on Smith’s Bible translation activities more clearly integrates them with his other scriptures and his ongoing work of targumizing the Bible.