Limitation of Vt and Pl(es) by volume-controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.

Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

BackgroundVentilator-associated conditions (VACs), for which new surveillance definitions and methods were issued by the Center for Disease Control and Prevention (CDC), are respiratory complications occurring in conjunction with the use of invasive mechanical ventilation and are related to adverse outcomes in critically ill patients. However, to date, risk factors for VACs have not been adequately established, leading to a need for developing a better understanding of the risks. The objective of this study was to explore care-related risk factors as a process indicator and provide valuable information pertaining to VAC preventive measures.MethodsThis retrospective, single-center, cohort study was conducted in the intensive-care unit (ICU) of a university hospital in Japan. Patient data were automatically sampled using a computerized medical records system and retrospectively analyzed. Management and care-related, but not host-related, factors were exhaustively analyzed using multivariate analysis for risks of VACs. VAC correlation to mortality was also investigated.ResultsOf the 3122 patients admitted in the ICU, 303 ventilated patients meeting CDC-specified eligibility criteria were included in the analysis. Thirty-seven VACs (12.2%) were found with a corresponding rate of 12.1 per 1000 ventilator days. Multivariate analysis revealed four variables related to patient care as risk factors for VACs: absence of intensivist participation in management of ventilated patients [adjusted HR (AHR): 7.325, P < 0.001)], using relatively higher driving pressure (AHR: 1.216, P < 0.001), development of edema (AHR: 2.145, P = 0.037), and a larger body weight increase (AHR: 0.058, P = 0.005). Furthermore, this research confirmed mortality differences in patients with VACs and statistically derived risks compared with those without VACs (HR: 2.623, P = 0.008).ConclusionFour risk factors related to patient care were clearly identified to be the key factors for VAC preventive measures.

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