Ventricular paced rhythm is thought to obscure the electrocardiographic diagnosis of acute coronary occlusion myocardial infarction. Our primary aim was to compare the sensitivity of the modified ...Sgarbossa criteria (MSC) to that of the original Sgarbossa criteria for the diagnosis of occlusion myocardial infarction in patients with ventricular paced rhythm.
In this retrospective case-control investigation, we studied adult patients with ventricular paced rhythm and symptoms of acute coronary syndrome who presented in an emergency manner to 16 international cardiac referral centers between January 2008 and January 2018. The occlusion myocardial infarction group was defined angiographically as thrombolysis in myocardial infarction grade 0 to 1 flow or angiographic evidence of coronary thrombosis and peak cardiac troponin I ≥10.0 ng/mL or troponin T ≥1.0 ng/mL. There were 2 control groups: the "non-occlusion myocardial infarction-angio" group consisted of patients who underwent coronary angiography for presumed type I myocardial infarction but did not meet the definition of occlusion myocardial infarction; the "no occlusion myocardial infarction" control group consisted of randomly selected emergency department patients without occlusion myocardial infarction.
There were 59 occlusion myocardial infarction, 90 non-occlusion myocardial infarction-angio, and 102 no occlusion myocardial infarction subjects (mean age, 72.0 years; 168 66.9% men). For the diagnosis of occlusion myocardial infarction, the MSC were more sensitive than the original Sgarbossa criteria (sensitivity 81% 95% confidence interval CI 69 to 90 versus 56% 95% CI 42 to 69). Adding concordant ST-depression in V4 to V6 to the MSC yielded 86% (95% CI 75 to 94) sensitivity. For the no occlusion myocardial infarction control group of ED patients, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 96% (95% CI 90 to 99) versus 97% (95% CI 92 to 99); negative likelihood ratio (LR) 0.19 (95% CI 0.11 to 0.33) versus 0.45 (95% CI 0.34 to 0.65); and positive LR 21 (95% CI 7.9 to 55) versus 19 (95% CI 6.1 to 59). For the non-occlusion myocardial infarction-angio control group, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 84% (95% CI 76 to 91) versus 90% (95% CI 82 to 95); negative LR 0.22 (95% CI 0.13 to 0.38) versus 0.49 (95% CI 0.35 to 0.66); and positive LR 5.2 (95% CI 3.2 to 8.6) versus 5.6 (95% CI 2.9 to 11).
For the diagnosis of occlusion myocardial infarction in the presence of ventricular paced rhythm, the MSC were more sensitive than the original Sgarbossa criteria; specificity was high for both rules. The MSC may contribute to clinical decisionmaking for patients with ventricular paced rhythm.
The p53 protein plays a passive and an active role in stem cells. The transcriptional activities of p53 for cell-cycle arrest and DNA repair are largely turned off in stem cells, but there is some ...indication that long-term stem-cell viability may require other p53-regulated functions. When p53 is activated in stem cells, it stops cell division and promotes the commitment to a differentiation pathway and the formation of progenitor cells. In the absence of any p53 activity, stem-cell replication continues and mistakes in the normal epigenetic pathway occur at a higher probability. In the presence of a functionally active p53 protein, epigenetic stability is enforced and stem-cell replication is regulated by commitment to differentiation. Over a lifetime of an organism, stem-cell clones compete in a tissue niche for Darwinian replicative advantages and in doing so accumulate mutations that permit stem-cell replication. Mutations in the p53 gene give stem cells this advantage, increase the clonal stem-cell population, and lower the age at which cancers can occur. Li-Fraumeni patients that inherit p53 mutations develop tumors in a tissue-type-specific fashion at younger ages. Throughout the life of a Li-Fraumeni patient, the tumor types that arise occur in tissues where stem cells are active and cell division is most rapid. Thus, p53 mutations that are inherited or occur during developmental life act in stem cells of the mesenchymal and epithelial lineages, whereas p53 mutations that occur in progenitor or differentiated (somatic) cells later in life function in tissues of endodermal origins, indicating that p53 may function differently in different developmental lineages.
Medication nonadherence is a common precipitant of heart failure (HF) hospitalization and is associated with poor outcomes. Recent analyses of national data focus on long-term medication adherence. ...Little is known about adherence of patients with HF immediately after hospitalization. Hospitalized patients with HF were identified from the Atherosclerosis Risk in Communities study. Atherosclerosis Risk in Communities data were linked to Medicare inpatient and part D claims from 2006 to 2009. Inclusion criteria were a chart-adjudicated diagnosis of acute decompensated or chronic HF; documentation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), β blocker (BB), or diuretic prescription at discharge; and Medicare part D coverage. Proportion of ambulatory days covered was calculated for up to twelve 30-day periods after discharge. Adherence was defined as ≥80% proportion of ambulatory days covered. We identified 402 participants with Medicare part D: mean age 75, 30% men, and 41% black. Adherence at 1, 3, and 12 months was 70%, 61%, and 53% for ACEI/ARB; 76%, 66%, and 62% for BB; and 75%, 68%, and 59% for diuretic. Adherence to any single drug class was positively correlated with being adherent to other classes. Adherence varied by geographic site/race for ACEI/ARB and BB but not diuretics. In conclusion, despite having part D coverage, medication adherence after discharge for all 3 medication classes decreases over 2 to 4 months after discharge, followed by a plateau over the subsequent year. Interventions should focus on early and sustained adherence.
Methane (CH4) fluxes from Alaska and other arctic regions may be sensitive to thawing permafrost and future climate change, but estimates of both current and future fluxes from the region are ...uncertain. This study estimates CH4 fluxes across Alaska for 2012–2014 using aircraft observations from the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE) and a geostatistical inverse model (GIM). We find that a simple flux model based on a daily soil temperature map and a static map of wetland extent reproduces the atmospheric CH4 observations at the statewide, multiyear scale more effectively than global‐scale process‐based models. This result points to a simple and effective way of representing CH4 fluxes across Alaska. It further suggests that process‐based models can improve their representation of key processes and that more complex processes included in these models cannot be evaluated given the information content of available atmospheric CH4 observations. In addition, we find that CH4 emissions from the North Slope of Alaska account for 24% of the total statewide flux of 1.74 ± 0.26 Tg CH4 (for May–October). Global‐scale process models only attribute an average of 3% of the total flux to this region. This mismatch occurs for two reasons: process models likely underestimate wetland extent in regions without visible surface water, and these models prematurely shut down CH4 fluxes at soil temperatures near 0°C. Lastly, we find that the seasonality of CH4 fluxes varied during 2012–2014 but that total emissions did not differ significantly among years, despite substantial differences in soil temperature and precipitation.
Key Points
A simple model of soil temperature and wetland distribution can reproduce patterns in atmospheric CH4 observations
The largest CH4 fluxes in Alaska occur in lowland tundra—in the southwest (e.g., Yukon‐Kuskokwim Delta) and North Slope
We do not find evidence for large year‐to‐year variability in total CH4 fluxes from Alaska
Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type, and tumor-type classifiers ...trained on genomic features have been explored, but the most accurate methods are not clinically feasible, relying on features derived from whole-genome sequencing (WGS), or predicting across limited cancer types. We use genomic features from a data set of 39,787 solid tumors sequenced using a clinically targeted cancer gene panel to develop Genome-Derived-Diagnosis Ensemble (GDD-ENS): a hyperparameter ensemble for classifying tumor type using deep neural networks. GDD-ENS achieves 93% accuracy for high-confidence predictions across 38 cancer types, rivaling the performance of WGS-based methods. GDD-ENS can also guide diagnoses of rare type and cancers of unknown primary and incorporate patient-specific clinical information for improved predictions. Overall, integrating GDD-ENS into prospective clinical sequencing workflows could provide clinically relevant tumor-type predictions to guide treatment decisions in real time.
We describe a highly accurate tumor-type prediction model, designed specifically for clinical implementation. Our model relies only on widely used cancer gene panel sequencing data, predicts across 38 distinct cancer types, and supports integration of patient-specific nongenomic information for enhanced decision support in challenging diagnostic situations. See related commentary by Garg, p. 906. This article is featured in Selected Articles from This Issue, p. 897.
The rising prevalence of antimicrobial resistance in
has rendered treatment of staphylococcal infections increasingly difficult, making the discovery of alternative treatment options a high priority. ...Peptidoglycan hydrolases, a diverse group of bacteriolytic enzymes, show high promise as such alternatives due to their rapid and specific lysis of bacterial cells, independent of antibiotic resistance profiles. However, using these enzymes for the systemic treatment of local infections, such as osteomyelitis foci, needs improvement, as the therapeutic distributes throughout the whole host, resulting in low concentrations at the actual infection site. In addition, the occurrence of intracellularly persisting bacteria can lead to relapsing infections. Here, we describe an approach using tissue-targeting to increase the local concentration of therapeutic enzymes in the infected bone. The enzymes were modified with a short targeting moiety that mediated accumulation of the therapeutic in osteoblasts and additionally enables targeting of intracellularly surviving bacteria.
A healthy 32-year-old woman presented with the acute onset of left sided eye pain, upper eyelid fullness, and binocular diplopia during light weightlifting. Examination elevated intraocular pressure, ...proptosis, upper eyelid ptosis, and motility deficits. CT demonstrated a well-circumscribed, homogeneous-appearing extraconal mass in the superior left orbit. The patient underwent an urgent orbitotomy with the excision of a hemorrhagic mass. Histopathology showed a glomus tumor with atypical features and hemorrhagic infarction, best classified as having uncertain malignant potential. A B-Raf proto-oncogene V600E mutation was detected with immunohistochemistry, which suggests a more aggressive tumor behavior yet presents an opportunity for targeted primary or adjunctive therapy. This is the first reported case of a B-Raf proto-oncogene-mutant atypical glomus tumor arising in the orbit.
The goal of this study was to estimate the population burden of heart failure and the influence of modifiable risk factors.
Heart failure is a common, costly, and fatal disorder, yet few studies have ...evaluated the population-level influence of modifiable risk factors.
From 14,709 ARIC (Atherosclerosis Risk in Communities) study participants, we estimated incidence rate differences (IRD) for the association between 5 modifiable risk factors (cigarette smoking, diabetes, elevated low-density lipoproteins, hypertension, and obesity) and heart failure. Potential impact fractions were used to measure expected changes in the heart failure incidence assuming achievement of a 5% proportional decrement in the prevalence of each risk factor.
Over an average of 17.6 years of follow-up, 1 in 3 African American and 1 in 4 Caucasian participants were hospitalized with heart failure, defined as the first hospitalization with International Classification of Diseases, Ninth Revision discharge codes of 428.x. Of the 5 modifiable risk factors, the largest IRD was observed for diabetes, which was associated with 1,058 (95% confidence interval CI: 787 to 1,329) and 660 (95% CI: 514 to 805) incident hospitalizations of heart failure/100,000 person-years among African-American and Caucasian participants, respectively. A 5% proportional reduction in the prevalence of diabetes would result in approximately 53 and 33 fewer incident heart failure hospitalizations per 100,000 person-years in African-American and Caucasian ARIC participants, respectively. When applied to U.S. populations, this reduction may prevent approximately 30,000 incident cases of heart failure annually.
Modest decrements in the prevalence of modifiable heart failure risk factors such as diabetes may substantially decrease the incidence of this major disease.
Background
Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive ...decline in a community-based sample may help clinicians understand disease risk.
Objective
To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline.
Design
This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years.
Participants
Among visit 5 (2011–2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996–1998).
Measurements
The primary outcome was cognitive status, classified as normal, mild cognitive impairment MCI, and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures.
Results
At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio RRR = 1.60 95% CI 1.13, 2.25) and MCI (RRR = 1.36 1.12, 1.64) than those without HF. A decline in cognition between visits 4 and 5 was − 0.07 standard deviation units − 0.13, − 0.01 greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction.
Conclusion
HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.
The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea ...syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS).
Retrospective chart review.
Tertiary academic medical center.
Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery.
Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012).
TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.
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