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      Fever as a first manifestation of acute aortic dissection

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          Abstract

          To the Editor, We enjoyed the recently published article by Jansen Klomp and colleagues [1], concerning the pitfalls in the differential diagnosis of acute aortic dissection (AAD). In their cohort, the authors report a high percentage of initially missed diagnoses, increased to 31%. Atypical symptoms and signs disorientate physicians during diagnosis. We would like to focus on the importance of fever, an often overlooked sign, which may accompany AAD. Although rarely described among the classic manifestations of AAD, pyrexia is observed in one-third of cases, frequently as a first sign, especially in cases of painless dissections. Fever development may start with rigor, either simultaneously with AAD or preceding it by several days. Patients frequently present with pyrexia of unknown origin. It is not uncommon for fever accompanying painless AAD to be erroneously attributed to respiratory infections, leading to empirical treatment with antibiotics. Body temperature is often above 39 °C and left pleural effusion on chest X‑ray is frequently seen. Left-sided effusions are due to irritation of the left pleura from its contact with the aorta, or even to leakage from the dissection per se [2]. Pericardial effusions are also frequent in this setting. Although the white cell count, erythrocyte sedimentation rate and C‑reactive protein values are raised in febrile AAD, procalcitonin values remain normal, excluding an infective aetiology. Pyrexia in the course of AAD is an ominous sign, related to high morbidity and mortality. Multi-arterial dissection is the rule, while death is the result of aortic rupture or multi-organ ischaemia and failure. As far as the origin of AAD-related fever is concerned, it seems that the formation of the pseudo-lumen recalls macrophages in the adventitia, with release of metalloproteinases and interleukin-6, which trigger a febrile immune-inflammatory mechanism [3]. It would be interesting to have some information about pyrexia in the cohort described by Jansen Klomp et al. [1]. Monitoring body temperature in patients fulfilling the criteria of potential AAD could develop into a reliable procedure of considerable diagnostic and prognostic value.

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          The molecular mechanisms contributing to the pathophysiology of systemic inflammatory response after acute aortic dissection.

          Type B acute aortic dissection (AAD) spares the ascending aorta and is optimally managed by medical therapy in the absence of complications. However, patients with enhanced inflammation sometimes present with aortic enlargement, thereby facing undesirable outcomes. Thus, a better understanding of the molecular and cellular mechanisms involved in AAD-associated inflammatory processes and the requirement for a novel therapeutic approach for patients with type B AAD are unmet clinical needs. This study showed that dissection per se induced neutrophil-chemoattractant chemokine expression in the aortic tunica adventitia, possibly by mechanical injury and stretching followed by pseudolumen formation. Subsequent systemic changes in chemokine-dependent signaling caused neutrophilia and massive neutrophil accumulation in the dissected aorta, thereby leading to aortic enlargement and rupture via interleukin-6 production. Importantly, temporal and spatial dynamics of inflammatory cytokine and chemokine elevation, as well as leukocyte recruitment, were consistent between rodents and humans. Our study provides a new mechanistic insight into neutrophil-mediated adventitial inflammation after AAD and implicates CXCR2- or interleukin-6 neutralization as novel therapeutic strategies to prevent large-artery complications, including aneurysm formation and rupture, in patients with type B AAD.
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            Clinical recognition of acute aortic dissections: insights from a large single-centre cohort study

            Aims Acute aortic dissection (AD) requires immediate treatment, but is a diagnostic challenge. We studied how often AD was missed initially, which patients were more likely to be missed and how this influenced patient management and outcomes. Methods A retrospective cohort study including 200 consecutive patients with AD as the final diagnosis, admitted to a tertiary hospital between 1998 and 2008. The first differential diagnosis was identified and patients with and without AD included were compared. Characteristics associated with a lower level of suspicion were identified using multivariable logistic regression, and Cox regression was used for survival analyses. Missing data were imputed. Results Mean age was 63 years, 39% were female and 76% had Stanford type A dissection. In 69% of patients, AD was included in the first differential diagnosis; this was less likely in women (adjusted relative risk [aRR]: 0.66, 95% CI: 0.44–0.99), in the absence of back pain (aRR: 0.51, 95% CI: 0.30–0.84), and in patients with extracardiac atherosclerosis (aRR: 0.64, 95% CI: 0.43–0.96). Absence of AD in the differential diagnosis was associated with the use of more imaging tests (1.8 vs. 2.3, p = 0.01) and increased time from admission to surgery (1.8 vs. 10.1 h, p < 0.01), but not with a difference in the adjusted long-term all-cause mortality (hazard ratio: 0.76, 95% CI: 0.46–1.27). Conclusion Acute aortic dissection was initially not suspected in almost one-third of patients, this was more likely in women, in the absence of back pain and in patients with extracardiac atherosclerosis. Although the number of imaging tests was higher and time to surgery longer, patient outcomes were similar in both groups. Electronic supplementary material The online version of this article (doi:10.1007/s12471-016-0921-8) contains supplementary material, which is available to authorized users.
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              Pyrexia in patients with uncontrolled systemic hypertension: could they have an aortic dissection?

              Aortic dissection can present in a variety of ways and one of the most documented risk factors includes systemic hypertension. Occasionally aortic dissection can be diagnosed late due to an insidious presentation. Fever has been described in people with aortic dissection but rarely as the main presenting feature. We present the cases of two patients with type B aortic dissections who shared three pertinent features which could have alerted the clinicians of the potential diagnosis; systemic hypertension, small left sided pleural effusion and a fever of unknown origin.
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                Author and article information

                Contributors
                sarvanitakis@doctors.net.uk
                Journal
                Neth Heart J
                Neth Heart J
                Netherlands Heart Journal
                Bohn Stafleu van Loghum (Houten )
                1568-5888
                1876-6250
                26 July 2017
                26 July 2017
                September 2017
                : 25
                : 9
                : 530
                Affiliations
                GRID grid.416145.3, Department of Cardiology, , Sotiria Chest Diseases Hospital, ; Athens, Greece
                Article
                1025
                10.1007/s12471-017-1025-9
                5571599
                28748413
                266c6fd2-7935-462a-bcbd-e92bd06f912c
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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                Letter to the Editor
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                © The Author(s) 2017

                Cardiovascular Medicine
                Cardiovascular Medicine

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