Healthcare team resilience during COVID-19: a qualitative study.

BACKGROUND: Resilience, in the field of Resilience Engineering, has been identified as the ability to maintain the safety and the performance of healthcare systems and is aligned with the resilience potentials of anticipation, monitoring, adaptation, and learning. In early 2020, the COVID-19 pandemic challenged the resilience of US healthcare systems due to the lack of equipment, supply interruptions, and a shortage of personnel. The purpose of this qualitative research was to describe resilience in the healthcare team during the COVID-19 pandemic with the healthcare team situated as a cognizant, singular source of knowledge and defined by its collective identity, purpose, competence, and actions, versus the resilience of an individual or an organization. METHODS: We developed a descriptive model which considered the healthcare team as a unified cognizant entity within a system designed for safe patient care. This model combined elements from the Patient Systems Engineering Initiative for Patient Safety (SEIPS) and the Advanced Team Decision Making (ADTM) models. Using a qualitative descriptive design and guided by our adapted model, we conducted individual interviews with healthcare team members across the United States. Data were analyzed using thematic analysis and extracted codes were organized within the adapted model framework. RESULTS: Five themes were identified from the interviews with acute care professionals across the US (N = 22): teamwork in a pressure cooker, consistent with working in a high stress environment; healthcare team cohesion, applying past lessons to present challenges, congruent with transferring past skills to current situations; knowledge gaps, and altruistic behaviors, aligned with sense of duty and personal responsibility to the team. Participants' described how their ability to adapt to their environment was negatively impacted by uncertainty, inconsistent communication of information, and emotions of anxiety, fear, frustration, and stress. Cohesion with co-workers, transferability of skills, and altruistic behavior enhanced healthcare team performance. CONCLUSION: Working within the extreme unprecedented circumstances of COVID-19 affected the ability of the healthcare team to anticipate and adapt to the rapidly changing environment. Both team cohesion and altruistic behavior promoted resilience. Our research contributes to a growing understanding of the importance of resilience in the healthcare team. And provides a bridge between individual and organizational resilience.

RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature.

Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome. We tested the signature in independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass data set, patients who were treated correctly according to the signature had a better progression-free survival (median, 20.1 months vs not reached; hazard ratio [HR], 0.40; confidence interval [CI], 0.23-0.72; P = .0012) and overall survival (median, 30.7 months vs not reached; HR, 0.41; CI, 0.21-0.80; P = .0049) than those who were not. Indeed, the outcome for these correctly treated patients was noninferior to that for those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.

A novel requirement for DROSHA in maintenance of mammalian CG methylation.

In mammals, faithful inheritance of genomic methylation patterns ensures proper gene regulation and cell behaviour, impacting normal development and fertility. Following establishment, genomic methylation patterns are transmitted through S-phase by the maintenance methyltransferase Dnmt1. Using a protein interaction screen, we identify Microprocessor component DROSHA as a novel DNMT1-interactor. Drosha-deficient embryonic stem (ES) cells display genomic hypomethylation that is not accounted for by changes in the levels of DNMT proteins. DNMT1-mediated methyltransferase activity is also reduced in these cells. We identify two transcripts that are specifically upregulated in Drosha- but not Dicer-deficient ES cells. Regions within these transcripts predicted to form stem-loop structures are processed by Microprocessor and can inhibit DNMT1-mediated methylation in vitro. Our results highlight DROSHA as a novel regulator of mammalian DNA methylation and we propose that DROSHA-mediated processing of RNA is necessary to ensure full DNMT1 activity. This adds to the DROSHA repertoire of non-miRNA dependent functions as well as implicating RNA in regulating DNMT1 activity and correct levels of genomic methylation.

A Single Controlled Exposure to Secondhand Smoke May Not Alter Thrombogenesis or Trigger Platelet Activation.

INTRODUCTION: Chronic secondhand smoke (SHS) exposure increases cardiovascular events, particularly acute thrombotic events. There are little human data on acute SHS exposure. The aim of this study was to determine whether a single controlled exposure of humans to SHS increased thrombogenesis. METHODS: After 6-8 hours fast, subjects (n = 50) were exposed to constant dose SHS (particulate level of 500 µg/m(3)) for 120 minutes in a temperature-regulated and ventilated, simulated bar environment. Blood was drawn before and immediately after SHS exposure for thromboelastography (TEG) and flow cytometry. Maximum clot strength (MA) was measured using TEG and platelet leukocyte aggregates (LPA) were measured as an index of platelet activation. Anti-CD 14 antibodies were used as leukocyte markers and anti-CD 41 antibodies as platelet markers for cytometry. Data were analyzed using students' t test for paired samples. RESULTS: There was no effect of acute exposure to SHS on platelet activation or thrombogenesis. Also, intra group (smokers [n = 19] and nonsmokers [n = 31]) comparisons of LPA and TEG parameters did not show changes with SHS exposure. CONCLUSIONS: While there are abundant data showing enhanced thrombogenesis and platelet activation following repeated exposure to SHS, our study suggests that a single exposure does not appear to significantly alter thrombin kinetics nor result in platelet activation. The effects of SHS on thrombogenesis might be nonlinear.

Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.

AIMS: There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke. METHODS AND RESULTS: We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3. CONCLUSION: In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

Mechanisms of coronary thrombosis in cigarette smoke exposure.

Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

Femoral micropuncture or routine introducer study (FEMORIS).

OBJECTIVES: The Micropuncture® 21-gauge needle may reduce complications related to vessel trauma from inadvertent venous or posterior arterial wall puncture. METHODS: This was a single-center, multiple-user trial. Four hundred and two patients undergoing possible or definite percutaneous coronary intervention (PCI) were randomized 1:1 to an 18-gauge versus a 21-gauge needle. Patients and personnel pulling the sheaths and performing the follow-up were blinded. The primary end point was a composite of access bleeding. Events were tabulated following sheath removal, ≤ 24 h after the procedure and at the follow-up (at 1-2 weeks). End points were blindly adjudicated. RESULTS: The event rate overall was 12.4% and did not differ significantly between groups, although the 21-gauge needle was found to reduce events by more than one third. An exploratory subgroup analysis of prespecified variables indicated that: patients who did not undergo PCI or elective procedures, female patients and those with a final sheath size of ≤ 6 Fr all had a significant or near-significant reduction of complications with Micropuncture. CONCLUSIONS: Although no significant differences between the use of the 18- and 21-gauge needles were observed, there was a 50-75% reduction with Micropuncture in several subgroups. The study was terminated prematurely. Access site complications may be reduced by the use of the 21-gauge needle, particularly when the risk of bleeding is not high. Further multicenter data will be required to confirm these hypothesis-generating observations.

Heat exhaustion and heat stroke among active component members of the U.S. Armed Forces, 2019-2023.

The most serious types of heat illnesses, heat exhaustion and heat stroke, are occupational hazards associated with many of the military's training and operational environments. These illnesses can typically be prevented by appropriate situational awareness, risk management strategies, along with effective countermeasures. In 2023, the crude incidence of heat stroke and heat exhaustion were 31.7 and 172.7 cases per 100,000 person-years, respectively. The rates of incident heat stroke declined during the 2019 to 2023 surveillance period, but rates of incident heat exhaustion increased over the same period. In 2023, higher rates of heat stroke were observed among male service members compared to their female counterparts, and female service members experienced higher rates of heat exhaustion compared to male personnel. Heat illness rates were also higher among those younger than age 20, Marine Corps and Army service members, non-Hispanic Black service members, and recruits. Leaders, training cadres, and supporting medical and safety personnel must inform their subordinate and supported service members of heat illness risks, preventive measures, early signs and symptoms of illness, and appropriate interventions.

Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme.

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I-III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance. METHODS: The genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type. RESULTS: No subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is 'probably pathogenic', based on control frequency <0.23%, identification in trans to a pathogenic/probably pathogenic mutation and segregation with USH in only one family; and UV3 ('likely pathogenic') as above, but no information on phase. Overall 79% of identified pathogenic/UV4/UV3 variants were truncating and 21% were missense changes. MYO7A accounted for 53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7. CONCLUSIONS: One or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

Identifying and Treating Vulnerable Atherosclerotic Plaques.

Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a disrupted plaque (usually a thin-capped fibroatheroma) or an eroded atherosclerotic plaque. These thrombus-prone plaques are vulnerable or high-risk. Although, traditionally, cardiologists have concentrated on treating significant coronary obstruction, there has been great interest over the last 2 decades in possibly preventing the thrombotic causes of myocardial infarction/sudden coronary death by mostly identifying and stabilizing these asymptomatic vulnerable or high-risk plaques, which, at least on invasive angiography, are mostly nonobstructive. Computed tomographic angiography and intravascular imaging during invasive coronary angiography have now been shown to identify a majority of these vulnerable or high-risk plaques before symptoms, thus opening up new preventive strategies. In conclusion, this article discusses the identification and management of these thrombus-prone lesions and patients with these lesions either with noninvasive techniques and systemic therapies or possibly through a new and bold interventional paradigm.

Active Surveillance for Acute Respiratory Disease Detected No Outbreaks at Four U.S. Army Basic Training Installations in 2022.

Abstract: A total of 254 febrile acute respiratory disease (ARD) cases were identified among Army basic trainees in 2022. No Army basic training installations met the definition for an ARD or Group A Beta-Hemolytic Streptococcus outbreak in 2022. The inclusion of afebrile ARD data in the surveillance program identified an additional 1,696 cases in which a trainee met the criteria for a case of ARD, except for an oral temperature of 100.5°F or higher. While including afebrile cases in the ARD rate calculation did result in an overall increase in weekly ARD rates, no basic training installations met the MEDCOM definition for an ARD outbreak. The continued surveillance and implementation of interventions such as chemoprophylaxis, vaccination, and non-pharmacologic interventions (e.g. hand-washing, head-to-toe sleeping bunk arrangement, etc.) helped identify and potentially prevent ARD outbreaks. What are the new findings?: In 2022, no ARD outbreaks were identified at any U.S. Army basic training installations, according to the U.S. Army's Medical Com-mand (MEDCOM) definition. This marks the third consecutive year without an ARD outbreak at these installations. Vaccination, chemoprophylaxis, and active disease surveillance are cornerstones of the Army's program to protect the health and readiness of basic trainees, utilizing support from the Defense Health Agency's Defense Centers for Public Health. What is the impact on readiness and force health protection?: U.S. Army basic training provides an ideal environment for the development of respiratory disease outbreaks because of sustained high stress combined with close trainee living and training quarters. Disease outbreaks degrade force readiness by increasing training time or potentially reducing numbers of trainees who graduate. The data from 2020 through 2022 demonstrate that no ARD outbreaks occurred in this population.

In Search of Coronary Thrombosis as the Cause of Myocardial Infarction: Unraveling a 20th-Century Mystery.

For the greater part of the 20th century, the pathophysiology of acute myocardial infarction regarding whether thrombosis was either present or primary was debated until 1973 when pathologists and clinicians met and by consensus, finally decided that the data supported that transmural infarction (what we now refer to as ST elevation myocardial infarction or STEMI) was caused by thrombus in the vessel supplying the infarcted territory. As the data for this consensus came from pathological analysis, it took another 7 years until angiographic and interventional data in humans with acute presentations of transmural infarction convincingly indicated that thrombus was indeed responsible. Subsequently, in patients presenting with either syndromes of unstable angina or nontransmural (later called non-ST elevation) myocardial infarction, it was established through angiographic and other interventional approaches that thrombus formation was also causative in a substantial proportion of these patients. This article reviews the history and this search for causation of myocardial infarction that now has resulted in present therapies that have saved innumerable lives over the last 30 to 40 years.

A systematic concept analysis of healthcare team resilience in times of pandemic disasters.

BACKGROUND: The concept of resilience has been used as a descriptor for individuals and organizations with the dominant themes of bouncing back and moving forward. AIMS: To examine the concept of resilience in providers and healthcare teams during pandemic disasters. RESEARCH DESIGN: Walker and Avant's eight-step concept analysis method. DATA SOURCE: CINAHL, EBSCO Host, PubMed, and SCOPUS were searched using the combined terms "resilience" or "resiliency" or "resilient" and "healthcare professionals," or "healthcare worker" or "healthcare team" or "physician" or "nurse" or "doctor" and "pandemic" or "disaster." METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Checklist was used to review the literature and apply findings using the eight-step Walker and Avant method for concept analysis. RESULTS: Three clusters emerged as attributes of individual resilience that may be applied to healthcare teams in times of pandemic disasters: (1) resilience is a dynamic contextual process, (2) resilience stabilizes the team to maintain a routine level of function, and (3) resilience is a catalyst for the actualization of innate or acquired skills and ability within the healthcare team. CONCLUSION: This analysis suggests that resilience enhances the healthcare team's ability to maintain function during acute changes created by pandemic disasters. Resilience in healthcare teams during pandemics requires future research to explore the phenomenon.

Suicide behavior among heterosexual, lesbian/gay, and bisexual active component service members in the U.S. Armed Forces.

Lesbian, gay, and bisexual (LGB) individuals are at a particularly high risk for suicidal behavior in the general population of the United States. This study aims to determine if there are differences in the frequency of lifetime suicide ideation and suicide attempts between heterosexual, lesbian/gay, and bisexual service members in the active component of the U.S. Armed Forces. Self-reported data from the 2015 Department of Defense Health-Related Behaviors Survey were used in the analysis. Multivariable logistic regression demonstrated that lesbian/gay and bisexual service members were more likely to report past suicide ideation when compared to heterosexual service members (adjusted odds ratio [AOR] for lesbian/gay: 1.79; 95% CI:1.14-2.82; AOR for bisexual: 2.33; 95% CI: 1.56-3.49). Similar results were observed for past suicide attempt for lesbian/gay (AOR: 2.29; 95% CI: 1.15-4.57) and bisexual SMs (AOR: 2.04; 95% CI: 1.24-3.38). Despite disparities in suicide ideation and attempt by sexual orientation, a majority of service members' behavioral health questionnaires do not assess sexual orientation. Clinical screenings of suicide risk in military settings should factor in sexual orientation to more comprehensively assess association between sexual orientation and suicidal behavior in this population.

Estimates of Direct Medical and Indirect Costs Associated With COVID-19 Among U.S. Active Duty Army Soldiers.

INTRODUCTION: This study estimated the direct medical and indirect costs associated with coronavirus disease 2019 (COVID-19) diagnoses among U.S. active duty (AD) Army service members (SMs). These cost estimates provide the U.S. Military with a better understanding of the financial burden of COVID-19 and provide a foundation for cost-effectiveness estimates. MATERIALS AND METHODS: The study was approved as Public Health Practice (#17-605) by the U.S. Army Public Health Center, Public Health Review Board. U.S. AD Army SMs with COVID-19 were identified using an Army COVID-19 testing and surveillance database. Encounters for these SMs were captured from medical record where International Classification of Disease Tenth Revision, Clinical Modification code U07.1 was in the first or second diagnostic position. Analyses were conducted on SMs with COVID-19 who either had no healthcare encounters in the Military Health System (MHS); at least one MHS COVID-19 inpatient hospitalization; or at least one MHS outpatient COVID-19 encounter. Coronavirus disease 2019 (COVID-19) costs captured from the encounters were used to develop direct medical cost estimates. Literature on COVID-19 recovery post-hospitalization, along with the number of COVID-19 hospitalizations and outpatient visits from encounters were used to describe the intensity of COVID-19 care. Estimates of the indirect cost of lost duty were based on SMs salary information, along with recovery time, bed days, or outpatient visit time. The indirect cost of limited duty was estimated using the time associated with the Department of Defense (DoD) COVID-19 pandemic mitigation strategies in place when these SMs were identified as positive for COVID-19. RESULTS: Coronavirus disease 2019 (COVID-19) cost estimates were developed for the Army using data from 19,086 SMs identified as positive for COVID-19 between June 1, 2020, and December 31, 2020. Direct medical costs, or the amount paid by the DoD to facilities for COVID-19 care, averaged $606 per SM with an encounter. Indirect costs for lost duty or the cost for recovery and the time taken to seek care for COVID-19 averaged $319 per SM, while indirect costs for limited duty or isolation associated with COVID-19 averaged $4,111 per SM or $411 per day. Service members (SMs) with an inpatient hospitalization averaged 4.8 bed days (range 1-43) and 266 recovery hours while SMs who sought outpatient care for COVID-19 averaged two outpatient visits (range 1-60 visits). CONCLUSIONS: The direct medical costs of a COVID-19 encounter in the MHS ($606) are a small portion of the costs for a SM with COVID-19. Indirect costs of lost and limited duty associated with COVID-19 averaged seven times higher ($4,331) and accounted for the vast majority of costs. Recognition of these costs is important especially given that soldiers in the hospital or in quarters being quarantined are complete losses of manpower to the Army. While the COVID-19 pandemic is ongoing and prevention, treatment, and mitigation efforts continue to evolve, having reliable estimates of direct medical and indirect costs from this study allows the U.S. Army and MHS to better account for the cost of this pandemic for its population.

New Precordial T Wave Inversions in Hospitalized Patients.

BACKGROUND: The incidence of precordial T changes has been described in athletes and in specific populations, while the etiology in a large patient population admitted to the hospital has not previously been reported. METHODS: All electrocardiograms (ECGs) read by the same physician with new (compared to prior ECGs) or presumed new (no prior ECGs) precordial T wave inversions of >1 mm (0.1 mV) in multiple precordial leads were retrospectively reviewed and various ECG, patient-related, and imaging parameters assessed. A total of 226 patients and their ECGs were initially selected for analysis. Of these, 35 were eliminated leaving 191 for the final analysis. RESULTS: Patients and their ECGs were divided into 5 groups based on diagnosis and incidence including Wellens syndrome, takotsubo, type 2 myocardial infarction, other (including multiple diagnoses), and unknown. Although subtle differences including number of T inversion leads, depth of T waves, QTc intervals, and other variables were present between some groups, diagnosis in individual cases required appropriate clinical, laboratory, or imaging studies. For example, although Wellens syndrome was identified in <20% of cases, a presenting history of chest discomfort with precordial T changes either on the admission or next-day ECG was highly sensitive and specific for this diagnosis. In some cases, type 2 myocardial infarction can also have a Wellens-like ECG phenotype without significant left anterior descending disease. CONCLUSIONS: Precordial T wave changes in hospitalized patients have various etiologies, and in individual cases, the changes on the ECG alone cannot easily distinguish the presumptive diagnosis and additional data are required.

Comparison and imputation-aided integration of five commercial platforms for targeted DNA methylome analysis.

Targeted bisulfite sequencing (TBS) has become the method of choice for the cost-effective, targeted analysis of the human methylome at base-pair resolution. In this study, we benchmarked five commercially available TBS platforms-three hybridization capture-based (Agilent, Roche and Illumina) and two reduced-representation-based (Diagenode and NuGen)-across 11 samples. Two samples were also compared with whole-genome DNA methylation sequencing with the Illumina and Oxford Nanopore platforms. We assessed workflow complexity, on/off-target performance, coverage, accuracy and reproducibility. Although all platforms produced robust and reproducible data, major differences in the number and identity of the CpG sites covered make it difficult to compare datasets generated on different platforms. To overcome this limitation, we applied imputation and show that it improves interoperability from an average of 10.35% (0.8 million) to 97% (7.6 million) common CpG sites. Our study provides guidance on which TBS platform to use for different methylome features and offers an imputation-based harmonization solution that allows comparative, integrative analysis.

Acute myocardial infarction and the five-chambered heart.

The case of a patient presenting with acute inferior ST-elevation myocardial infarction is described. Emergent coronary angiography of the right coronary artery revealed what appeared to be the abrupt drainage of contrast into a large, peculiar cavity or chamber. Echocardiography and cardiac computed tomography demonstrated a giant right coronary aneurysm in the right coronary artery that gave the impression of a "fifth heart chamber." The patient underwent successful surgical resection of the aneurysm. Diagnostic and treatment approaches to giant coronary aneurysms are discussed.