Frequency and outcomes of STEMI patients presenting between 12 and 24 h after symptom onset: Late-presenting STEMI.

OBJECTIVES: To assess the characteristics and prognosis of ST-elevation myocardial infarction (STEMI) patients, presenting between 12 and 24 h after symptom onset, in contemporary regional STEMI systems of care in the United States. BACKGROUND: Previous observational studies have been inconsistent regarding the benefit of primary percutaneous coronary intervention (PCI) compared with conservative management for late-presenting STEMI patients and the majority of randomized trials are from the fibrinolytic era. METHODS: Using a two-center registry-based cohort from March 2003 to December 2020, we evaluated the frequency, clinical characteristics, and outcomes of STEMI patients, stratified by symptom onset to balloon time: <3, 3-6, 6-12, and 12-24 h (late presenters). RESULTS: Among 5427 STEMI patients with available symptom onset time, 6.2% were late presenters, which increased to 11% during the early phase of the Covid-19 pandemic. As symptom onset to balloon time increased, patients were more likely to be older, female, and have a history of hypertension and diabetes mellitus. Late presenters with an identifiable culprit lesion were less likely to be revascularized with PCI (96%, 96%, 95%, and 92%; p for trend = 0.004) and had a longer median door-to-balloon time (82, 109, 107, and 117 min; p for trend < 0.001). In-hospital and 1-year death risks were comparable between late and earlier presenters. CONCLUSION: Despite the unfavorable risk profile and longer door-to-balloon time, clinical outcomes of late presenters were similar to those presenting within 12 h of symptom onset.

Literature review of distal deep vein thrombosis.

OBJECTIVE: Although distal deep vein thrombosis (DDVT) has been more frequently diagnosed with the availability of better ultrasound imaging quality, the data on the best method to manage DDVT have been conflicting. The aim of the present review was to summarize the current and evidence-based recommendations for the diagnosis and management of DDVT and to provide a summary of the most recent societal guideline recommendations. METHODS: A literature review of DDVT was performed. The PubMed databases were queried for articles on the epidemiology, risk factors, diagnosis, and management of DDVT. RESULTS: The prevalence of isolated DDVT has been reported in a broad range. The reported risk factors include older age, active malignancy, a low degree of mobility, acute infection, and atrial fibrillation. With more evidence, anticoagulation therapy was found to be associated with a reduced risk of recurrent venous thromboembolism (VTE) and/or thrombus propagation compared with conservative management. However, anticoagulation was associated with an increased risk of bleeding in a number of studies. The rate of VTE recurrence ranged from 7% to 23% during a follow-up period ranging from 3 months to 8 years. The significant risk factors for VTE recurrence included cancer, older age, an unprovoked event, and inpatient status. CONCLUSIONS: Few studies have addressed the diagnosis and management of DDVT. Further research is needed to standardize the best approach to diagnose and treat DDVT.

Lipid-lowering therapies in peripheral artery disease: A review.

Peripheral artery disease (PAD) is estimated to affect approximately 8.5 million individuals in the US above the age of 40, and is associated with significant morbidity, mortality, and impairment. Despite the significant adverse limb and cardiovascular (CV) outcomes seen in patients with PAD, there is typically less attention paid to risk factor modification relative to other atherosclerotic diseases such as coronary artery disease (CAD) or stroke. In the current literature, statins have been shown to reduce mortality, major adverse CV events, major adverse limb events, and improve symptomatic outcomes in patients with PAD. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are emerging as an additional lipid-lowering therapy for patients with PAD. However, despite current guideline recommendations based on growing evidence, patients with PAD are consistently undertreated with lipid-lowering therapies. We provide an extensive literature review and evidence-based recommendations for the use of statins and PCSK9 inhibitors in patients with PAD.

Risk and Management of Venous Thromboembolism in Patients with COVID-19.

BACKGROUND: One of the most pronounced and poorly understood pathological features of COVID-19 infection has been high risk for venous and arterial thromboembolic complications. An increasing number of thromboembolic events are being reported almost on a daily basis, and the medical community has struggled to predict and mitigate this risk. We aimed to review available literature on the risk and management of COVID-19 related venous thromboembolism (VTE), and provide evidence-based guidance to manage these events. METHODS: A literature review of VTE complications in patients with COVID-19 was performed, in addition to a summary of the societal guidelines and present pathways implemented at our institution for the management of both in- and outpatient COVID-19 related VTE. RESULTS: Although a significant VTE risk has been confirmed in patients with COVID-19, literature addressing best ways to mitigate this risk is lacking. Furthermore, there has been very limited guidance provided by societal guidelines to help prevent and manage VTE associated with the COVID-19 infection. In light of the available data, we advise that all patients admitted with suspected or confirmed COVID-19 receive pharmacological prophylaxis if bleeding risk is acceptable. For patients with COVID-19 who have been discharged from the emergency department or hospital, we suggest extended thromboprophylaxis (up to 39 days) as long as bleeding risk is low. CONCLUSIONS: We believe that this literature summary along with our center recommendations and algorithms provide valuable guidance to providers caring for patients with COVID-19 related VTE. More research is needed to standardize prophylaxis and management protocols for these patients.

Purification of Transcript-Specific mRNP Complexes Formed In Vivo from Saccharomyces cerevisiae.

RNA binding proteins play critical roles in shaping the complex life cycle of cellular transcripts. For most RNAs, the association with a distinct complement of proteins serves to orchestrate its unique pattern of maturation, localization, translation, and stability. A key aspect to understanding how transcripts are differentially regulated lies, therefore, in the ability to identify the particular repertoire of protein binding partners associated with an individual transcript. We describe here an optimized experimental procedure for purifying a single mRNA population from yeast cells for the characterization of transcript-specific mRNA-protein complexes (mRNPs) as they exist in vivo. Chemical cross-linking is used to trap native mRNPs and facilitate the co-purification of protein complexes associated with an individual transcript population that is captured under stringent conditions from cell lysates through hybridization to complementary DNA oligonucleotides. The resulting mRNP is highly enriched and largely devoid of non-target transcripts, and can be used for a number of downstream analyses including protein identification by mass spectrometry.

Nonsense-mediated RNA decay--a switch and dial for regulating gene expression.

Nonsense-mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD-sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady-state RNA levels in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein-coding capacity are also sensitive to this translation-dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways.

Translation of small open reading frames within unannotated RNA transcripts in Saccharomyces cerevisiae.

High-throughput gene expression analysis has revealed a plethora of previously undetected transcripts in eukaryotic cells. In this study, we investigate >1,100 unannotated transcripts in yeast predicted to lack protein-coding capacity. We show that a majority of these RNAs are enriched on polyribosomes akin to mRNAs. Ribosome profiling demonstrates that many bind translocating ribosomes within predicted open reading frames 10-96 codons in size. We validate expression of peptides encoded within a subset of these RNAs and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent nonsense-mediated RNA decay (NMD) pathway. We identify lncRNAs that are also sensitive to NMD, indicating that translation of noncoding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein coding and expand the proteome of yeast and possibly other eukaryotes.