Rsy [14,23]. Moreover, many studies were performed in trauma or surgical patients.

Rsy [14,23]. Moreover, many studies were performed in trauma or surgical patients. Serological positivity for CMV Autophagy reported in critically ill patients ranged from 13 [39] to 100 [40]. Respiratory samples positive for CMV ranged from 0 [41] to 13 [4], antigenemia ranged from 0 [42] to 17 [14], and even 85 in one study [23]. However, the use of open lung biopies found that up to 50 of patients with ARDS were infected with CMV [16]. These differences could be explained by different diagnostic methods for the detection of CMV, including viral culture, antigenemia and PCR assays [22]. Previous studies used culture-based assays (low sensitivity and time-consuming), whereas more recent studies have used antigenemia (more sensitive and quantitative results) or PCR assays [13]. Nevertheless, none of these methods have been validated in ICU patients. Moreover, our results should take in account the relative lack of sensitivity and specificity of some of these diagnostic methods (serology for example). It was likely that some patients with positive virus may actually have infection, whereas other with positive samples may just be false positive. The newest diagnostic methods have not been validated in ICU patients. However, in immunocompromised patients, techniques such as PCR and antigenemia present an adequate diagnostic accuracy [43,44]. CMV reactivation in intensive care patients is not trivial. Indeed, in a study using a murine model, Cook et al. showed that CMV reactivation caused abnormal tumor necrosis factora expression and induced abnormal pulmonary fibrosis, both of which were prevented with ganciclovir [45]. Reactivation of CMV could lead to an increased duration of ventilation or ICU stay in non-immunosuppressed patients in an intensive care setting [2,14,23,24,46,47]. A human study found an independent correlation between CMV reactivation and morbidity in nonimmunosuppressed patients [17], however, there was no correlation with mortality. Another human study found a significant increased mortality rate in patients expressing CMV, but could notdemonstrate a cause-effect relationship [20]. In our study, we could identify factors associated with positive CMV samples, but causative links between both had not been addressed. To our knowledge, this is the first study indicating that an active CMV infection in critical care patients increased crude and adjusted mortality at day 60. Our results are concordant with those of Heininger et al. [4], who found that the mortality rate tended to be higher in patients with active CMV infections, with a significant increase in ICU length of stay in survivors. Limaye [13] also found and association between CMV reactivation and a composite end point (prolonged hospitalization or death). In our unit, all patients with an active CMV infection were treated with gancyclovir, which make it Autophagy difficult 15755315 to conclude regarding the efficacy of this treatment. Only an interventional trial could conclude if CMV is definitely responsible for a longer duration of mechanical ventilation/LOS. Indeed, a longer duration of exposure to mechanical ventilation could be associated with an increased risk to identify CMV without any impact on prognosis. This is unlikely because in the present study, patients from the control group were ventilated invasively for a longer period than the time to identify CMV in the CMV group. Figures 2 and 3 represent two meta-analyses of the mortalities associated with CMV and HSV. Even if.Rsy [14,23]. Moreover, many studies were performed in trauma or surgical patients. Serological positivity for CMV reported in critically ill patients ranged from 13 [39] to 100 [40]. Respiratory samples positive for CMV ranged from 0 [41] to 13 [4], antigenemia ranged from 0 [42] to 17 [14], and even 85 in one study [23]. However, the use of open lung biopies found that up to 50 of patients with ARDS were infected with CMV [16]. These differences could be explained by different diagnostic methods for the detection of CMV, including viral culture, antigenemia and PCR assays [22]. Previous studies used culture-based assays (low sensitivity and time-consuming), whereas more recent studies have used antigenemia (more sensitive and quantitative results) or PCR assays [13]. Nevertheless, none of these methods have been validated in ICU patients. Moreover, our results should take in account the relative lack of sensitivity and specificity of some of these diagnostic methods (serology for example). It was likely that some patients with positive virus may actually have infection, whereas other with positive samples may just be false positive. The newest diagnostic methods have not been validated in ICU patients. However, in immunocompromised patients, techniques such as PCR and antigenemia present an adequate diagnostic accuracy [43,44]. CMV reactivation in intensive care patients is not trivial. Indeed, in a study using a murine model, Cook et al. showed that CMV reactivation caused abnormal tumor necrosis factora expression and induced abnormal pulmonary fibrosis, both of which were prevented with ganciclovir [45]. Reactivation of CMV could lead to an increased duration of ventilation or ICU stay in non-immunosuppressed patients in an intensive care setting [2,14,23,24,46,47]. A human study found an independent correlation between CMV reactivation and morbidity in nonimmunosuppressed patients [17], however, there was no correlation with mortality. Another human study found a significant increased mortality rate in patients expressing CMV, but could notdemonstrate a cause-effect relationship [20]. In our study, we could identify factors associated with positive CMV samples, but causative links between both had not been addressed. To our knowledge, this is the first study indicating that an active CMV infection in critical care patients increased crude and adjusted mortality at day 60. Our results are concordant with those of Heininger et al. [4], who found that the mortality rate tended to be higher in patients with active CMV infections, with a significant increase in ICU length of stay in survivors. Limaye [13] also found and association between CMV reactivation and a composite end point (prolonged hospitalization or death). In our unit, all patients with an active CMV infection were treated with gancyclovir, which make it difficult 15755315 to conclude regarding the efficacy of this treatment. Only an interventional trial could conclude if CMV is definitely responsible for a longer duration of mechanical ventilation/LOS. Indeed, a longer duration of exposure to mechanical ventilation could be associated with an increased risk to identify CMV without any impact on prognosis. This is unlikely because in the present study, patients from the control group were ventilated invasively for a longer period than the time to identify CMV in the CMV group. Figures 2 and 3 represent two meta-analyses of the mortalities associated with CMV and HSV. Even if.