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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Both short and long sleep duration have been associated with an increased prevalence and incidence of cancer&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1&#44;2</span></a> but its relationship with cancer aggressiveness remains unknown&#46; We have previously described an association between cutaneous melanoma and sleep-disordered breathing based on a prospective multicentric cohort&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> In the present paper&#44; we describe the results of a post-hoc analysis aiming to evaluate the association between subjective sleep duration and objective parameters of melanoma aggressiveness&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This is an observational&#44; cross-sectional&#44; multicenter study that included 443 consecutive patients with a diagnosis of melanoma from 29 Spanish hospitals&#46; Patients were excluded if they had in situ melanoma or had received previous treatment with continuous positive airway pressure&#46; The study was approved by the ethics committees of all the hospitals&#44; and all the patients gave their informed consent&#46; Each patient completed a clinical questionnaire which included anthropometric measurements&#44; relevant antecedents&#44; medication&#44; sleep apnea symptoms&#44; presence of insomnia and somnolence &#40;Epworth Sleepiness Scale&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Sleep duration was assessed by asking the patients the following question&#58; How many hours of sleep &#40;including naps&#41; have you had on average in a 24-h period during the last year &#40;year prior to the diagnosis of melanoma&#41;&#63; Participants estimated habitual sleep duration using full hour units&#46; Snoring time was also quantified in the sleep study records&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All patients underwent a sleep study by means of a home respiratory polygraphy and a peripheral blood test&#46; Patients were divided into three groups depending on their daily sleep duration&#58; appropriate sleep duration &#40;between 6 and 8<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; short sleepers &#40;&#60;6<span class="elsevierStyleHsp" style=""></span>h&#41; and long sleep duration &#40;&#62;8<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; The independent relationship between melanoma aggressiveness factors and sleep duration was determined by introducing into a multivariate logistical regression analysis those variables which could&#44; in the opinion of the researchers&#44; also have clinical importance as confounders&#58; age&#44; sex&#44; AHI&#44; BMI and hypnotics intake&#46; This relationship was evaluated by Hazard Ratio &#40;CI95&#37;&#41;&#44; considering the group of patients with appropriate sleep duration as the control group&#46; The degree of melanoma aggressiveness was measured by histological variables such as the Breslow thickness&#44; the tumor mitotic rate &#40;&#8805;5 vs&#46; &#60;5 mitoses per mm<span class="elsevierStyleSup">2</span>&#41;&#44; the histological presence of ulceration and regression and positive sentinel lymph node &#40;SLN&#41; involvement&#46; The cut-off points for the Breslow thickness were established at 1&#44; 2 and 4<span class="elsevierStyleHsp" style=""></span>mm&#44; according to international guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">443 patients were finally included in the study&#46; Mean age was 55&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;3 years&#44; and 50&#46;6&#37; were male&#46; The mean BMI was 27&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> and the median Epworth score was 6 &#40;IQR&#58; 3&#8211;8&#41;&#46; The median of the Breslow thickness was 0&#46;85<span class="elsevierStyleHsp" style=""></span>mm &#40;IQR&#58; 0&#46;49&#8211;1&#46;80&#41;&#46; A Breslow thickness above 1&#44; 2 and 4<span class="elsevierStyleHsp" style=""></span>mm was found in&#44; respectively&#44; 44&#44; 22&#46;3 and 8&#46;8&#37; of the patients&#46; Ulceration was present in 16&#37;&#44; regression in 23&#46;3&#37;&#44; and SLN was positive in 10&#46;6&#37; of patients&#46; The median AHI was 8&#46;6 &#40;IQR&#58; 2&#46;8&#8211;20&#46;2&#41;&#46; The mean sleep duration was 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;27<span class="elsevierStyleHsp" style=""></span>h&#44; with 4&#46;7&#37; sleeping &#60;6<span class="elsevierStyleHsp" style=""></span>h&#44; 77&#46;9&#37; between 6 and 8<span class="elsevierStyleHsp" style=""></span>h and 17&#46;4&#37;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>h&#46; 8&#46;4&#37; of the patients presented insomnia and 12&#37; were taking hypnotic drugs&#46; The sleep study time was 7&#46;2<span class="elsevierStyleHsp" style=""></span>h &#40;IQR&#58; 6&#46;6&#8211;8&#41; and the snoring study time was 6&#46;9<span class="elsevierStyleHsp" style=""></span>h &#40;IQR&#58; 6&#46;5&#8211;7&#46;7&#41;&#46; The correlation between subjective sleep duration and snoring study time was <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;86&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">There was a statistically significant correlation between sleep duration and the Breslow index &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;26&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Those patients with more aggressive melanoma &#40;Breslow<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mm vs &#60;2<span class="elsevierStyleHsp" style=""></span>mm&#44; and Breslow<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mm versus &#60;4<span class="elsevierStyleHsp" style=""></span>mm&#41; presented longer sleep duration &#40;8&#46;1 vs&#46; 7&#46;1<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001 and 8&#46;3 vs&#46; 6&#46;9<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#44; respectively&#41;&#46; Long sleepers presented&#44; in comparison with those patients who slept less than 8<span class="elsevierStyleHsp" style=""></span>h&#44; a significant increase in various systemic markers of inflammation like high-sensitivity C-reactive protein &#40;hs CRP&#41; &#40;2&#46;35 &#91;2&#46;3&#41; vs 1&#46;33 &#91;2&#46;5&#93; mg&#47;L&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; fibrinogen concentration &#40;392 &#91;97&#46;1&#93; vs&#46;335 &#91;92&#46;7&#93; mg&#47;dL&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and erythrocyte sedimentation rate &#40;ESR&#41; &#40;17&#46;4 &#91;13&#46;9&#93; vs&#46; 11&#46;2 &#91;9&#46;1&#93; mm1<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; as well as a higher AHI &#40;19&#46;8 &#91;17&#46;9&#93; vs&#46; 15&#46;1 &#91;16&#46;1&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows that long sleepers were 1&#46;53&#44; 1&#46;72 and 2&#46;84 times more likely to present a more aggressive melanoma &#40;Breslow index above 1&#44; 2 and 4<span class="elsevierStyleHsp" style=""></span>mm&#41; compared to the control group&#44; after adjustment for age&#44; gender&#44; BMI&#44; AHI&#44; intake of hypnotic drugs and presence of insomnia&#46; Similarly&#44; long sleepers had an increased risk of SLN positive&#44; presence of tumor ulceration and a high tumor mitotic rate&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">As far as we know&#44; this is the first study to analyze the relationship between longer sleep duration and the aggressiveness of a cancer&#46; Of note&#44; this association was not caused by the presence of confounders such as obesity&#44; sleep apnea&#44; age&#44; gender&#44; hypnotics intake or insomnia&#46; Various mechanisms have been postulated to explain this relationship&#44; including various deregulations of the immune system &#40;especially reductions in natural killer cell activity&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> increased sleep fragmentation<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> and increased systemic inflammation&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">6&#44;7</span></a> In fact&#44; our study shows that long sleepers presented greater systemic inflammation &#40;increased levels of US-CRP&#44; ESR and fibrinogen&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The main limitation of our study was the fact that the evaluation of sleep duration was subjective&#44; as is the case in most of the similar studies published to date on this topic&#46; However&#44; there was a very strong correlation between the subjective sleep duration and the snoring study time &#40;while the patients are supposed to be sleeping&#41;&#46; Moreover&#44; some authors<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> have observed in large series that those patients with self-reported sleep<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>h per night overestimated their real sleep duration by an average of 0&#46;3<span class="elsevierStyleHsp" style=""></span>h&#44; while this overestimate was even higher &#40;1&#46;3<span class="elsevierStyleHsp" style=""></span>h&#41; in patients who slept<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>h&#46; These circumstances would minimize any error derived from our analysis since&#44; even assuming this situation&#44; the vast majority of the patients in our study would remain in the same analysis group&#46; Moreover&#44; the percentage of patients with abnormal sleep time was 22&#37;&#44; which could affect the conclusions&#46; Finally&#44; we did not include the presence of anxiety or depression as a covariate&#44; but we did include the intake of hypnotics and other psychotropic medication&#44; which is closely associated with anxiety and depression&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; we found for the first time a positive relationship between a long sleep duration and some markers of melanoma aggressiveness&#46; Future studies are needed to investigate the main pathophysiological mechanisms that could explain this association and the prognostic relevance of this finding&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have nothing to declare in relation to this manuscript&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Relationship between sleep duration and commonly used clinical markers of tumor aggressiveness in cutaneous melanoma&#46; <span class="elsevierStyleItalic">p</span> values refer to sleep duration<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>h versus control group &#40;sleep duration between 6 and 8<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Results were adjusted for age&#44; sex&#44; apnea-hypopnea index&#44; body mass index&#44; presence of insomnia and intake of hypnotics&#46; SL&#58; Short sleep&#59; LS&#58; Long Sleep&#46;</p>"
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