Is Verubecestat Actually Worth The Verubecestat?

Globally, 26% of all deaths in the age group of 15�C44 years in 2002 were due to injury.[1,2,3] In India, trauma is a major problem, due to a very high incidence of vehicular accidents, other selleck accidents, injuries, crimes, and violence.[1,2,4] Infections are one of the most important causes of mortality and morbidity in traumatized patients. Despite early effective treatment, such patients are susceptible to developing sepsis and multiple organ failure, which in turn are the major causes of death in these critically ill patients.[5,6,7,8,9] Monocytes have been found to play a key role in immunological response to the bacterial infections.[10,11] Systemic inflammation, as well as immune suppression, are thought to play a decisive role in the development of sepsis and multiple organ dysfunction syndromes. As the paradigm of sepsis pathogenesis has evolved over time, and our understanding of the different therapeutic approaches to sepsis developed, various biomarkers have been used for diagnosis of sepsis and monitoring of treatment. The diagnosis of sepsis is still a challenge till date due to the highly variable nature of its signs, symptoms, and unreliable performance of the available biomarkers.[12] Early diagnosis and stratification of the severity of sepsis will increase the possibility of appropriate and timely treatment.[13] The secretion of pro-inflammatory mediators results in an inadequately regulated inflammation. Pro-inflammatory cytokines such as tumor Verubecestat necrosis factor-alpha (TNF-��) and interleukin-6 (IL-6) have been implicated as principal mediators of monocytic activity and probably major mediators involved in the pathogenesis of sepsis.[7,8,9,14] Most of the studies on the evaluation of the role of TNF-�� and IL-6 have been done using plasma, which depicts extracellular pooled levels.[15] These assays may give an erroneous interpretation. Moreover, the cellular origin cannot be ascertained in these extracellular assays. Oxymatrine Given the importance of sepsis diagnosis and the lacunae thereof, the present study was designed to assess the activity of monocytes with respect to production of TNF-�� and IL-6 by flow cytometry in critically ill septic patients admitted to the Intensive Care Unit (ICU) of a level-1 trauma center and to correlate it with the patients�� outcomes. MATERIALS AND METHODS A prospective study was conducted from March 2013 to July 2013. Patient selection Patients enrolled in the present study were those whose blood cultures (one or more) had grown aerobic gram-negative pathogen/s and further fulfilled the criteria for clinical diagnosis of sepsis. The presence of sepsis was confirmed when at least two of the following four clinical signs of sepsis were present: (a) Temperature >38.9��C or 32 torr; (c) heart rate >100 beats/min; (d) white blood cells >15,000 or