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1.
Heart Lung Circ ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32439246

RESUMO

BACKGROUND: Patients aged ≥80 years old often present to Emergency Departments (ED) with symptoms potentially due to an acute coronary syndrome (ACS). This study aimed to evaluate associations between baseline level(s) of high sensitivity troponin T (HsTnT), adjudicated diagnoses and outcomes. METHODS: Consecutive patients aged ≥80 years were studied, who presented to the ED at Liverpool Hospital, NSW, Australia during the 4 months period March to June 2014 (inclusive) with symptoms suggestive of an ACS, and who had at least one HsTnT assay performed. Diagnoses were based on the fourth universal definition of MI (myocardial infarction) including type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury; the rest were termed "other diagnoses". Patients were categorised by baseline HsTnT levels 1) ≤14 ng/L, 2) 15-29 ng/L, 3) 30-49 ng/L and 4) ≥50 ng/L. RESULTS: Of 2,773 patients screened, 545 were aged ≥80 years (median age 85 [IQR 82-88]); median follow-up was 32 months (IQR 5-56). The respective rates of adjudicated diagnoses were type-I MI 3.1%, type-2 MI 13%, acute myocardial injury 9.5%, chronic myocardial injury 56% and 18.6% had other diagnoses. Mortality rates increased, irrespective of adjudicated diagnoses with increasing HsTnT levels (ng/L): 17% (16/96) for ≤14; 35% (67/194) for 15-29; 51% (65/127) for 30-49; and 64% (82/128) for ≥50 ng/L; log rank p≤0.001. On multi-variable analyses, after adjusting for potential confounding factors including age, hypertension, chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), MI type was not associated with late mortality. CONCLUSIONS: Among patients aged ≥80 years higher HsTnT levels, irrespective of adjudicated diagnoses, were associated with increased mortality. Most very elderly patients presenting with symptoms suggestive of an ACS undergoing HsTnT testing in EDs had elevated levels most commonly due to chronic myocardial injury. Whether any interventions can modify outcomes require prospective evaluation.

3.
Vet Radiol Ultrasound ; 61(3): 364-369, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31916651

RESUMO

Positron emission tomography (PET) imaging utilizing fluorine-18 labeled fluorodeoxyglucose is a relatively new imaging modality in veterinary medicine that is becoming more common for oncological staging and for musculoskeletal imaging. Thus, it is important to identify the normal variations on PET imaging that may be mistaken for pathology. Variation in standardized uptake values (SUVmax) have been anecdotally identified in the spinal cord of dogs undergoing fluorodeoxyglucose (FDG) PET-CT examinations for oncological staging, with notable increase in SUVmax values identified in the region of the cervical and lumbar spinal intumescences. The aim of this retrospective, analytical study was to compare the SUVmax values at four different locations throughout the spinal cord (C3, C5-T1, T13, and L3-S1) of a group of dogs with no evidence of neurologic disease and compare those findings to histologic specimens from dogs euthanized for unrelated disease. SUVmax values were significantly higher at the cervical and lumbar intumescences in comparison to the control regions (P < .0001 and P < .0001, respectively). Neuronal count and spinal cord gray matter area were also significantly greater at the cervical and lumbar intumescences (neuronal count P = .0025 and P = .0001; area P = .0004 and P = .0009, respectively) while overall neuronal density was lower (P = .003 and P = .028, respectively). We presume the increased SUVmax values at the spinal cord intumescences are the result of overall increased neuron count, increased proportion of gray matter, and increased spinal cord gray matter area. These findings will aid in the interpretation of future PET-CT studies and hopefully prevent the misdiagnosis of spinal cord disease in normal canines.

4.
Vet Radiol Ultrasound ; 61(1): 33-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31596018

RESUMO

Computed tomographic angiography (CTA) has recently been shown to be a useful tool in the diagnosis of acute canine pancreatitis, the identification of pancreatic necrosis, and the detection of sequelae. Evidence of pancreatic necrosis on CTA has been shown to be correlated with a poorer outcome in both humans and dogs and early diagnosis and intervention may improve outcomes. In humans, pancreatic necrosis is typically evident on CTA within 48 h of clinical signs, thus, repeat CTA examinations are often performed to identify pancreatic necrosis that may not have been evident on CTA examinations performed early in the course of disease. Published information investigating the timing of CTA examinations and the use of serial CTA in dogs with acute pancreatitis is lacking. In this prospective, longitudinal study, CTA examinations were performed at the time of hospitalization and repeated 3-5 days later in 11 dogs suffering from acute canine pancreatitis to determine if pancreatic necrosis or sequelae are under diagnosed on examinations performed at the time of hospitalization. Computed tomographic angiography studies were evaluated for changes in pancreatic size, pancreatic contrast enhancement, and peri-pancreatic tissues and vessels. The only statistically significant difference between the initial and repeat CTA examinations was the improvement of fat stranding on the repeat CTA examinations (P < .045). Based on these results, CTA performed at the time of admission is likely adequate in the diagnosis and evaluation of dogs with acute pancreatitis. Repeat CTA examinations are unlikely to add additional information in the absence of worsening clinical signs.

5.
Eur Heart J Qual Care Clin Outcomes ; 6(1): 41-48, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111144

RESUMO

AIMS: As assessment of patients with suspected acute coronary syndromes (ACS) in emergency departments (EDs) represents a major workload because high-sensitivity troponin (HsTn) T and I levels are frequently measured, and a minority of patients have final diagnosis of myocardial infarction (MI). We determined the relative frequencies of three patients groups: Type-I MI, Type-II MI (including acute myocardial injury). METHODS AND RESULTS: Among 2738 consecutive patients with suspected ACS presenting to ED at Liverpool Hospital, Australia, between March and June 2014. We studied the use of invasive and pharmacological therapies, and 4-year outcomes. Adjudication of MI was according to the 4th universal definition as follows: (i) Type-I MI; (ii) Type-II MI (including acute myocardial injury), and (iii) chronic myocardial injury. Of 995 patients (36%) [median age 76 years (interquartile range 65-83)] with ≥2 HsTnT measurements and one >14 ng/L, 727 (73%) had chronic myocardial injury, 171 (17%) had Type-II MI, and 97 (9.7%) had Type-I MI; respective late mortality rates to 48 months were 33%, 43%, and 14% (P < 0.001). In-hospital angiography rates were 95% for patients with Type-I MI, [62% had percutaneous coronary intervention (PCI)] 24% (7% PCI) for those with Type-II MI, and 3.4% for chronic myocardial injury. On Cox modelling for mortality relative to Type 1 MI, adjusted hazard ratios were 1.94 [95% confidence intervals (CIs) 1.06-3.57]; P = 0.032 for Type 2 MI, and for chronic myocardial injury 1.14 (95% CIs 0.64-2.02); P = 0.66. CONCLUSION: Among unselected patients undergoing HsTnT testing in EDs, Type-II MI including acute myocardial injury was more common than Type-I MI. Chronic myocardial injury, which occurred in three of four patients. Whereas patients with Type-II MI had higher late mortality than those with Type-I MI, after multivariable analyses mortality rates were marginally different.

6.
Heart Lung Circ ; 29(3): 460-468, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31060910

RESUMO

BACKGROUND: Identifying predictors of bleeding in patients before coronary artery bypass grafting surgery is important, given the complications of bleeding and finite supply of blood. Patient response to aspirin is heterogeneous and can be evaluated using point-of-care platelet function tests. We postulated that patients who hyper-respond to aspirin given preoperatively, as identified by VerifyNow® Aspirin assay (Accumetrics, Inc., San Diego, CA, USA), are at increased risk of bleeding and transfusion. METHODS: This prospective pilot study examined response to aspirin in patients undergoing coronary artery bypass grafting surgery (n = 61) from 2009 to 2013. Patients with aspirin reaction unit (ARU) values in the lower 50th percentile as identified by VerifyNow® assays were defined as aspirin hyper-responders. The proportion of patients transfused and the median adjusted indexed drop in haemoglobin were compared between aspirin hyper-responders and non-hyper-responders. Logistic regression was performed to determine factors associated with increased risk of transfusion. RESULTS: Seventy per cent (70%) of aspirin hyper-responders were transfused perioperatively compared with 39% of patients who did not hyper-respond, (OR 3.694, 95% CI 1.275-10.706, p = 0.014). VerifyNow® Aspirin hyper-responders had a greater median adjusted indexed drop in haemoglobin compared to non-hyper-responders (34.1 g/L versus 26.6 g/L respectively, p = 0.032). Multivariate analysis also showed VerifyNow® Aspirin hyper-response to be an independent predictor of transfusion (p = 0.016). Other variables such as age, gender, body mass index, renal insufficiency, and cross clamp and bypass times were not predictors of postoperative bleeding in this pilot cohort. CONCLUSIONS: VerifyNow® Aspirin is able to preoperatively identify aspirin hyper-responders at an increased risk of bleeding and subsequent transfusion in the context of coronary artery bypass graft surgery.

7.
J Med Imaging Radiat Sci ; 50(4S2): S20-S23, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648963

RESUMO

Innovations in artificial intelligence (AI) are driving a new industrial revolution, and as a result, the medical radiation sciences is experiencing transformational, open, beneficial, yet disruptive changes. Many studies have already been published on specific frontline examples where AI will improve cancer care, but discussions of how AI will change the medical radiation sciences and its associated professions at the systems level have been comparatively sparse. In this article, the system-level implications of AI on the medical radiation sciences are discussed, and recommendations are made on how professionals in this field may need to adapt in preparation for a future where AI will be an integral part of the health care system at all levels.

8.
Circulation ; 140(19): 1543-1556, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31478763

RESUMO

BACKGROUND: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED). METHODS: Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression. RESULTS: In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49-70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P<0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4-6.4] hours versus standard arm: 5.6 (interquartile range, 4.0-7.1) hours, P<0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P<0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 17/1646 [1.0%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53-2.11], noninferiority P value=0.006, superiority P value=0.867), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0-99.9%) for 30-day death or myocardial infarction. CONCLUSIONS: This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au. Unique identifier: ACTRN12615001379505.

9.
JAMA Cardiol ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532457

RESUMO

Importance: Current guidelines recommend evaluation for echocardiographically estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg; however, this threshold does not capture all patients at risk. Objectives: To determine if mild echocardiographic pulmonary hypertension (ePH) is associated with reduced right ventricular (RV) function and increased risk of mortality. Design, Setting, and Participants: In this cohort study, electronic health record data of patients who were referred for echocardiography at Vanderbilt University Medical Center, Nashville, Tennessee, from March 1997 to February 2014 and had recorded estimates of RVSP values were studied. Data were analyzed from February 2017 to May 2019. Exposures: Mild ePH was defined as an RVSP value of 33 to 39 mm Hg. Right ventricular function was assessed using tricuspid annular plane systolic excursion (TAPSE), and RV-pulmonary arterial coupling was measured using the ratio of TAPSE to RVSP. Main Outcomes and Measures: Associations of mild ePH with mortality adjusted for relevant covariates were examined using Cox proportional hazard models with restricted cubic splines. Results: Of the 47 784 included patients, 26 758 of 47 771 (56.0%) were female and 6040 of 44 763 (13.5%) were black, and the mean (SD) age was 59 (18) years. Patients with mild ePH had worse RV function compared with those with no ePH (mean [SD] TAPSE, 2.0 [0.6] cm vs 2.2 [0.5] cm; P < .001) and nearly double the prevalence of RV dysfunction (32.6% [92 of 282] vs 16.7% [170 of 1015]; P < .001). Compared with patients with RVSP less than 33 mm Hg, those with mild ePH also had reduced RV-pulmonary arterial coupling (mean [SD] ratio of TAPSE to RVSP, 0.55 [0.18] mm/mm Hg vs 0.93 [0.39] mm/mm Hg; P < .001). An increase in adjusted mortality began at an RVSP value of 27 mm Hg (hazard ratio, 1.32; 95% CI, 1.02-1.70). Female sex was associated with increased mortality risk at any given RVSP value. Conclusions and Relevance: Mild ePH was associated with RV dysfunction and worse RV-pulmonary arterial coupling in a clinical population seeking care. Future studies are needed to identify patients with mild ePH who are susceptible to adverse outcomes.

10.
Fitoterapia ; 137: 104281, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381957

RESUMO

Veratrum californicum is a rich source of steroidal alkaloids, many of which have proven to be antagonists of the Hedgehog (Hh) signaling pathway that becomes aberrant in over twenty types of cancer. These alkaloids first became known in the 1950's due to their teratogenic properties, which resulted in newborn and fetal lambs developing cyclopia as a result of pregnant ewes consuming Veratrum californicum. It was discovered that the alkaloids in V. californicum were concentrated in the root and rhizome of the plant with much lower amounts of the most active alkaloid, cyclopamine, present in the aerial plant, especially in the late growth season. Inspired by the limitations in analytical instrumentation and methods available to researchers at the time of the original investigation, we have used state-of-the-art instrumentation and modern analytical methods to quantitate four steroidal alkaloids based on study parameters including plant part, harvest location, and growth stage. The results of the current inquiry detail differences in alkaloid composition based on the study parameters, provide a detailed assessment for alkaloids that have been characterized previously (cyclopamine, veratramine, muldamine and isorubijervine), and identify at least six alkaloids that have not been previously characterized. This study provides insight into optimal harvest time, plant growth stage, harvest location, and plant part required to isolate, yet to be characterized, alkaloids of interest for exploration as Hh pathway antagonists with desirable medicinal properties.


Assuntos
Alcaloides/química , Esteroides/química , Veratrum/química , Alcaloides/isolamento & purificação , Proteínas Hedgehog/antagonistas & inibidores , Idaho , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química , Rizoma/química , Estações do Ano , Esteroides/isolamento & purificação , Alcaloides de Veratrum
11.
Intern Med J ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424594

RESUMO

BACKGROUND: Cardiac troponin assays are a very widely requested test, particularly in emergency departments. Thus, many seriously ill patients who may not have heart disease as their primary discharge diagnosis have undergone troponin testing during hospitalisation. METHODS AND RESULTS: Over a 2-year period (2006-2008) 172,753 hospitalised patients had a quantatitive or qualitative troponin assay performed in New South Wales (Australia). The associations were examined, using data linked to late outcomes, between elevations in levels of troponins T or I and 1-year mortality. Mortality was determined for International Statistical Classification of Diseases 10th Revision (ICD-10-AM) diagnostic groups. Of 172,753 patients undergoing troponin testing 44,357 (25%) had a cardiovascular diagnosis of whom (7% had myocardial infarction) 47,827 (28%) had a probable ischaemic heart disease (IHD) diagnosis if the 23,873 (14%) of patients coded with 'chest pain' were included. In patients with a cardiovascular diagnosis and elevated troponin 3,060 (1.8%) died in 12 months in comparison to 6,262 (3.6%) in those with a non-cardiovascular disease diagnoses and elevated troponin. The 1-year mortality hazard with respect to a troponin elevation was 2.5 (95% Conficence Interval (CI) 2.3-2.7) and 2.0 [95% CIs 1.99-2.01] for those with a cardiovascular and non-cardiovascular diagnosis, respectively. CONCLUSION: In a very large state-wide hospitalised patient cohort, among patients with elevated troponin levels and non-cardiac diagnoses, mortality was higher than in those with cardiovascular diagnoses, including MI. This article is protected by copyright. All rights reserved.

12.
Int J Cardiol ; 296: 21-25, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31451306

RESUMO

BACKGROUND: The Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-Vessel Disease (FREEDOM) clinical trial randomized only a proportion of screened patients with diabetes mellitus (DM) and multi-vessel disease (MVD). METHODS AND RESULTS: We determined late rates of death, non-fatal myocardial infarction (MI) and stroke in all 430 patients with DM who had MVD identified on angiographic screening for the FREEDOM Trial, which recruited from June 2006 -March 2010 at Liverpool Hospital, Sydney, Australia. Mortality at 6 years [median] was 23% among 192 FREEDOM-eligible patients and 26% among 238 FREEDOM-ineligible patients, of whom 139 [58%] had prior. CABG (mortality 31%). Overall, 196 (45%) had percutaneous coronary intervention (PCI), 127 (30%) underwent coronary artery bypass grafting (CABG) (who were 4 years younger; p = 0.003), and 107 (25%) had neither procedure of whom 80 were considered unsuitable for revascularization. Mortality was 26% post-PCI 16%, post-CABG and 33% among those who did not undergo revascularization (p = 0.01). On multivariable analyses, factors associated with late mortality were older age, hypertension and not undergoing CABG (all p < 0.05). Factors associated with late MI were presented with an acute coronary syndrome, whereas patients that underwent treatment with either PCI or CABG had less late MI (all p < 0.05). CONCLUSION: Among consecutive diabetic patients with MVD, at a median of 6-years CABG was associated with better survival and fewer non-fatal MI outcomes compared to PCI.

13.
Int J Cardiol Heart Vasc ; 24: 100395, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321288

RESUMO

Aims: Left ventricular (LV) thrombus is a complication of acute ST-segment elevation myocardial infarction (STEMI). We determined the incidence and predictors of LV thrombus formation using serial cardiac magnetic resonance (CMR) and two-dimensional echocardiography studies. Methods and results: Two hundred and ten patients underwent CMR (median 4 days [IQR 3-7]) and transthoracic echocardiography (median 4 days [IQR 3-7]) early after STEMI presentation with serial follow-up CMR (median 55 days [IQR 46-64]) and echocardiography studies (median 54 days [IQR 45-64]) performed subsequently. The incidence of LV thrombus was 12.3% (26/210) by CMR and 6.2% (13/210) by two-dimensional echocardiography. Echocardiography had 50% sensitivity and 100% specificity for LV thrombus detection compared to CMR. LV thrombus was found in 23.6% of patients with anterior STEMI (22/93). Ischaemic stroke occurred in 1.4% of patients (3/210). Patients with LV thrombus had lower baseline LV ejection fraction (LVEF) (34.9% vs 47.4%, p < 0.001). Microvascular obstruction was more common in patients with LV thrombus (77% vs 39%, p < 0.001). Patients with LV thrombus had increased LV dimensions with larger LV end-diastolic (19 ml [IQR 9-44] vs 6 ml [IQR -4-18], p < 0.001) and end-systolic volumes (10 ml [IQR 0-22] vs -4 ml [IQR -12-4], p < 0.001). Conclusion: CMR increases the detection of LV thrombi which standard echocardiography may underestimate. Serial studies post-STEMI may improve detection of LV thrombus, which is more prevalent in patients with anterior infarction, moderate LV dysfunction and adverse LV remodelling. This subgroup of patients may represent a high-risk group for targeted serial screening with CMR.

14.
J Med Imaging Radiat Sci ; 50(2): 243-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176432

RESUMO

PURPOSE: The safe delivery of radiation therapy is dependent in part on the provision and organization of oncology professionals. General recommendations for staffing of radiation oncologists, medical physicists, and radiation therapists have been published, but most of these provide little detail, especially in the case of radiation therapists (RTs). In Canada, there are no guidelines or national standards for the staffing of RTs, and there is a paucity of Canadian data on the existing staffing levels of RTs and the models used to establish these levels. This project sought to identify and compare the staffing models used for Canadian RTs, and the staffing levels and workload resulting from these models. METHODS AND MATERIALS: In January 2016, a survey was sent to managers of the 46 radiation treatment centres in Canada. This survey sought information on a range of staffing and practice variables for the fiscal year 2014/2015. Respondents were requested to provide the staffing model used for RTs at each centre and enough additional information to calculate the staffing levels and workload resulting from their staffing model. The survey included further variables that had the potential to influence staffing levels and workload, and centres were compared to establish if these variables did indeed impact staffing. RESULTS: Of the 46 centres contacted, 37 centres responded, representing an 80.4% response rate. Survey results showed there are a variety of ways used to determine staffing across the country. Twenty of the 37 responding centres include some type of workload measurement in their staffing model, whereas 17 centres base staffing solely on historic levels or operating funds. There is a great deal of variation in the staffing levels and workload of RTs in Canada, with staff at some centres planning and treating twice the number of patients as RTs at other centres. Radiation therapist staffing levels at most radiation treatment centres in Canada are below the level recommended in recent publications. Differences in staffing levels or workload could not be accounted for by treatment complexity, number of specialty programs, use of relief staff, or number of RTs working in specialty nontreatment roles. CONCLUSIONS: A high degree of variability in staffing levels and workload exists for RTs in Canada, which is not explained by differences in patterns of practice. It is likely that workload for RTs exceed safe levels at some Canadian centres. It is recommended that treatment centres use an up-to-date staffing model for RTs and continue to review staffing levels at regular intervals.

15.
Crit Pathw Cardiol ; 18(1): 10-15, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30747759

RESUMO

The TRAPID-AMI (High Sensitivity Cardiac Troponin T assay for rapid Rule-out of Acute Myocardial Infarction) study evaluated a rapid "rule-out" acute myocardial infarction (AMI). We evaluated what symptoms were associated with AMI as part of a substudy of TRAPID-AMI. There were 1282 patients evaluated from 12 centers in Europe, the United States of America, and Australia from 2011 to 2013. Multiple symptom variables were prospectively obtained and evaluated for association with the final diagnosis of AMI. Multivariate logistic regression analysis was done, and odds ratios (OR) were calculated. There were 213/1282 (17%) AMIs. Four independent predictors for the diagnosis of AMI were identified: radiation to right arm or shoulder [OR = 3.0; confidence interval (CI): 1.8-5.0], chest pressure (OR = 2.5; CI: 1.3-4.6), worsened by physical activity (OR = 1.7; CI: 1.2-2.5), and radiation to left arm or shoulder (OR = 1.7; CI: 1.1-2.4). In the entire group, 131 (10%) had radiation to right arm or shoulder, 897 (70%) had chest pressure, 385 (30%) worsened with physical activity, and 448 (35%) had radiation to left arm or shoulder. Duration of symptoms was not predictive of AMI. There were no symptoms predictive of non-AMI. Relationship between AMI size and symptoms was also studied. For 213 AMI patients, cardiac troponins I values were divided into 4 quartiles. Symptoms including pulling chest pain, supramammillary right location, and right arm/shoulder radiation were significantly more likely to occur in patients with larger AMIs. In a large multicenter trial, only 4 symptoms were associated with the diagnosis of AMI, and no symptoms that were associated with a non-AMI diagnosis.


Assuntos
Infarto do Miocárdio/diagnóstico , Troponina/sangue , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
16.
Nat Commun ; 10(1): 305, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659182

RESUMO

DNA methylation is an essential epigenetic process in mammals, intimately involved in gene regulation. Here we address the extent to which genetics, sex, and pregnancy influence genomic DNA methylation by intercrossing 2 inbred mouse strains, C57BL/6N and C3H/HeN, and analyzing DNA methylation in parents and offspring using whole-genome bisulfite sequencing. Differential methylation across genotype is detected at thousands of loci and is preserved on parental alleles in offspring. In comparison of autosomal DNA methylation patterns across sex, hundreds of differentially methylated regions are detected. Comparison of animals with different histories of pregnancy within our study reveals a CpG methylation pattern that is restricted to female animals that had borne offspring. Collectively, our results demonstrate the stability of CpG methylation across generations, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events in somatic tissues at loci whose expression is linked to the relevant biology.


Assuntos
Metilação de DNA/genética , Epigênese Genética , Prenhez/genética , Animais , Ilhas de CpG , Metilação de DNA/fisiologia , Feminino , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Gravidez , Prenhez/fisiologia , Fatores Sexuais , Especificidade da Espécie , Sequenciamento Completo do Genoma
19.
Int J Cardiol ; 276: 261-267, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30404726

RESUMO

BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI). METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction. RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols. CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.


Assuntos
Algoritmos , Eletrocardiografia , Glicopeptídeos/sangue , Infarto do Miocárdio/diagnóstico , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Tempo
20.
J Am Coll Cardiol ; 73(6): 629-638, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30428398

RESUMO

BACKGROUND: The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial demonstrated that for patients with diabetes mellitus (DM) and multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention with drug-eluting stents (PCI-DES) in reducing the rate of major adverse cardiovascular and cerebrovascular events after a median follow-up of 3.8 years. It is not known, however, whether CABG confers a survival benefit after an extended follow-up period. OBJECTIVES: The purpose of this study was to evaluate the long-term survival of DM patients with MVD undergoing coronary revascularization in the FREEDOM trial. METHODS: The FREEDOM trial randomized 1,900 patients with DM and MVD to undergo either PCI with sirolimus-eluting or paclitaxel-eluting stents or CABG on a background of optimal medical therapy. After completion of the trial, enrolling centers and patients were invited to participate in the FREEDOM Follow-On study. Survival was evaluated using Kaplan-Meier analysis, and Cox proportional hazards models were used for subgroup and multivariate analyses. RESULTS: A total of 25 centers (of 140 original centers) agreed to participate in the FREEDOM Follow-On study and contributed a total of 943 patients (49.6% of the original cohort) with a median follow-up of 7.5 years (range 0 to 13.2 years). Of the 1,900 patients, there were 314 deaths during the entire follow-up period (204 deaths in the original trial and 110 deaths in the FREEDOM Follow-On). The all-cause mortality rate was significantly higher in the PCI-DES group than in the CABG group (24.3% [159 deaths] vs. 18.3% [112 deaths]; hazard ratio: 1.36; 95% confidence interval: 1.07 to 1.74; p = 0.01). Of the 943 patients with extended follow-up, the all-cause mortality rate was 23.7% (99 deaths) in the PCI-DES group and 18.7% (72 deaths) in the CABG group (hazard ratio: 1.32; 95% confidence interval: 0.97 to 1.78; p = 0.076). CONCLUSIONS: In patients with DM and MVD, coronary revascularization with CABG leads to lower all-cause mortality than with PCI-DES in long-term follow-up. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/cirurgia , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/etiologia , Angiopatias Diabéticas/complicações , Stents Farmacológicos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
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