Acute respiratory distress syndrome as a precursor to post-intensive care syndrome

More than 6 million patients are cared for in an intensive care unit annually in the United States, and millions more internationally. Acute respiratory failure (ARF) is a common indication for intensive care unit admission, one that afflicts more than half of critically ill patients. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of ARF. With advances in care over the last 50 years, the majority of ARF and ARDS patients survive. The survivorship literature is largely one that describes functional impairments and reduced quality of life after critical illness. In this review article, we put forth the concept that ARDS is a precursor to post-intensive care syndrome, defined as new or worsening impairments in cognition, mental health, and/or physical health after critical illness. This "precursor" paradigm is suggested as a means to a better end for patients with ARDS, by detailing care provisions and strategies to optimize short-term and long-term outcomes

Functional outcomes, goals, and goal attainment amongst chronically critically ill long-term acute care hospital patients

Rationale Chronically critically ill patients admitted to a long-term acute care hospital (LTACH) setting are a vulnerable population of intensive care unit survivors. Little is known of the goals and functional outcomes achieved by patients after rehabilitation in the LTACH setting. Objectives We sought to examine patient goals and functional outcomes, including swallowing function, amongst ICU survivors admitted to an LTACH with a tracheostomy. Methods Prospective observational cohort study of chronic critically ill LTACH patients. Results Fifty elderly subjects with a median duration of intubation prior to tracheostomy of 13 days were enrolled. ICU-acquired weakness and cognitive impairment were present in 40 (80%) and 36 (72%) patients, as measured by the Medical Research Council scale and Montreal Cognitive Assessment, respectively. Mental health problems were also common, with 16 (32%) patients experiencing moderate to severe anxiety, 9 (18%) experiencing moderate to severe depression, and 11 (22%) reporting symptoms consistent with PTSD, according to the Hospital Anxiety and Depression Scale and Post-Traumatic Stress Syndrome 10-Questions Inventory, respectively. Pharyngeal dysfunction, as measured by Fiberoptic Endoscopic Evaluation of Swallow exam, was present in 37 (74%) patients. Patient goals, in decreasing order of frequency, included: eating and drinking, speaking, walking, returning home, and toileting. By LTACH discharge, goal attainment was variable, with 97% of those who ranked speaking as important able to speak, 88% able to eat and drink, yet only 21% were walking and 18% were able to self-toilet. Discharge to the home or acute rehabilitation setting, achieved in 52% of the population, was associated with greater strength, as measured by the total MRC score (p=0.002), as well as the EuroQOL domains of mobility (p=0.008) and self-care (p=0.04). Conclusions Goal attainment during this period of recovery was variable. The ability to speak, eat and drink, frequently identified as goals by these patients, were achieved, while functional goals such as walking were rarely achieved. These findings highlight the importance of identifying patient goals and setting realistic expectations informed by functional assessments when rehabilitating this vulnerable patient population in the LTACH and subsequent post-acute care settings

Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo