Nonalcoholic fatty liver disease (NAFLD) is characterized by a broad spectrum of clinical and histological presentations, ranging anywhere from simple steatosis to steatohepatitis. Of the patients with NAFLD, only a small fraction goes on to develop inflammation and fibrosis (i.e. NASH). Hence, understanding the underlying molecular mechanisms, which play part in progression of NAFLD and determine the disease severity, is extremely important. Almost two decades ago, Day and colleagues first described the "two-hit hypothesis" to explain progression of NAFLD. However, since then, the advances in field of molecular research have identified that NAFLD development and progression involves complex interplay of numerous determinants, including gut-derived signals, endoplasmic reticulum stress, adipose-derived adipokines, nutritional factors, hormonal imbalances and components of innate immunity which act in concert on genetically predisposed individuals to induce liver inflammation. This chapter reviews the different players of this "multiple-hit model".
Above-Cuff Vocalization (ACV) can be performed using any tracheostomy tube with a subglottic suction channel and is the only method to facilitate speech in patients with tracheostomies who require mechanical ventilation with cuff inflation. Current ACV literature is largely comprised of case series, with no studies assessing widespread implementation of ACV in the ICU setting. Our goal was to assess the feasibility of hospital-wide implementation of an ACV protocol using ACV-capable tracheostomy tubes and its impact on patient speech.
METHODS:We performed an observational before-and-after study in four ICUs at an academic tertiary care hospital. An ACV implementation protocol was developed by intensivists and speech-language pathologists. This protocol was introduced after hospital-wide transition to a tracheostomy tube with a subglottic channel as the default cuffed tube placed in ICU patients. All patients who underwent routine tracheostomy while in the Medical ICU, Heart and Vascular ICU, Neurologic ICU, or Trauma/Surgical ICU during the study period were included. In addition to data collection on ACV efficacy and safety, time-to-speech after tracheostomy was compared between the pre-transition and post-transition groups using the Wilcoxon Rank-Sum test.
RESULTS:Of 255 subjects who received tracheostomy while in an ICU during the study period, 167 underwent the procedure before the transition and 88 after. 101 of 167 (60%) patients achieved speech within 60 days before the transition compared to 52 of 88 (59%) after. Amongst patients who achieved speech, a significant decrease in median time-to-speech was observed after the transition, from 13 days (IQR 8-20) to 10 days (IQR 6-14) (p = 0.01). 18 of 52 (35%) patients who achieved speech post-transition did so using ACV, with the remainder using speaking valve. Of the 18 patients who spoke with ACV, 6 of 18 (33%) did not progress to speaking valve within the follow-up period. Of those who did, the median speech-days gained using ACV was 5 (IQR 4-9 days). ACV was successful in facilitating speech in 18 of 21 (86%) patients trialed, with no major complications.CONCLUSIONS: Routine implementation of ACV after tracheostomy is feasible, safe, and associated with earlier speech post-tracheostomy in a diverse cohort of critically ill patients.
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