Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.

Impact of Fiber-Based Enteral Nutrition on the Gut Microbiome of ICU Patients Receiving Broad-Spectrum Antibiotics: A Randomized Pilot Trial.

OBJECTIVES: Dietary fiber increases the abundance of bacteria that metabolize fiber into short-chain fatty acids and confers resistance against gut colonization with multidrug-resistant bacteria. This pilot trial estimated the effect of fiber on gut short-chain fatty acid-producing bacteria in the ICU. DESIGN: Randomized, controlled, open label trial. SETTING: Medical ICU. PATIENTS: Twenty ICU adults receiving broad-spectrum IV antibiotics for sepsis. INTERVENTION: 1:1 randomization to enteral nutrition with mixed soy- and oat-derived fiber (14.3 g fiber/L) versus calorie- and micronutrient-identical enteral nutrition with 0 g/L fiber. MEASUREMENTS: Rectal swabs and whole stools were collected at baseline and on study Days 3, 7, 14, and 30. The primary outcome was within-individual change in the cumulative relative abundance of short-chain fatty acid-producing taxa from baseline to Day 3 based on 16S sequencing of rectal swabs. The secondary outcome was Day 3 cumulative short-chain fatty acid levels based on mass spectrometry of whole stools. Analyses were all intent to treat. MAIN RESULTS: By Day 3, the fiber group received a median of 32.1 g fiber cumulatively (interquartile range, 17.6-54.6) versus 0 g fiber (interquartile range, 0-4.0) in the no fiber group. The median within-individual change in short-chain fatty acid producer relative abundance from baseline to Day 3 was +61% (interquartile range -51 to +1,688) in the fiber group versus -46% (interquartile range, -78 to +13) in the no fiber group (p = 0.28). Whole stool short-chain fatty acid levels on Day 3 were a median of 707 µg short-chain fatty acids/g stool (interquartile range, 190-7,265) in the fiber group versus 118 µg short-chain fatty acids/g stool (interquartile range, 22-1,195) in the no fiber group (p = 0.16). CONCLUSIONS: Enteral fiber was associated with nonsignificant trends toward increased relative abundance of short-chain fatty acid-producing bacteria and increased short-chain fatty acid levels among ICU patients receiving broad-spectrum IV antibiotics. Larger studies should be undertaken and our results can be used for effect size estimates.

Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH) during transient cessation of breathing, triples the risk for cardiovascular diseases. We used a phage display peptide library as an unbiased approach to investigate whether IH, which is specific to OSA, activates endothelial cells (ECs) in a distinctive manner. The target of a differentially bound peptide on ECs collected from OSA patients was identified as CD59, a major complement inhibitor that protects ECs from the membrane attack complex (MAC). A decreased proportion of CD59 is located on the EC surface in OSA patients compared with controls, suggesting reduced protection against complement attack. In vitro, IH promoted endothelial inflammation predominantly via augmented internalization of CD59 and consequent MAC deposition. Increased internalization of endothelial CD59 in IH appeared to be cholesterol-dependent and was reversed by statins in a CD59-dependent manner. These studies suggest that reduced complement inhibition may mediate endothelial inflammation and increase vascular risk in OSA patients.

The implementation of an early rehabilitation program is associated with reduced length of stay: A multi-ICU study.

INTRODUCTION: Survivors of critical illness face many potential long-term sequelae. Prior studies showed that early rehabilitation in the intensive care unit (ICU) reduces physical impairment and decreases ICU and hospital length of stay (LOS). However, these studies are based on a single ICU or were conducted with a small subset of all ICU patients. We examined the effect of an early rehabilitation program concurrently implemented in multiple ICUs on ICU and hospital LOS. METHODS: An early rehabilitation program was systematically implemented in five ICUs at the sites of two affiliated academic institutions. We retrospectively compared ICU and hospital LOS in the year before (1/2011-12/2011) and after (1/2012-12/2012) implementation. RESULTS: In the pre- and post-implementation periods, respectively, there were a total of 3945 and 4200 ICU admissions among the five ICUs. After implementation, there was a significant increase in the proportion of patients who received more rehabilitation treatments during their ICU stay (p < 0.001). The mean number of rehabilitation treatments per ICU patient-day increased from 0.16 to 0.72 (p < 0.001). In the post-implementation period, four of the five ICUs had a statistically significant decrease in mean ICU LOS among all patients. The overall decrease in mean ICU LOS across all five ICUs was 0.4 days (6.9%) (5.8 versus 5.4 days, p < 0.001). Across all five ICUs, there were 255 (6.5%) more admissions in the post-implementation period. The mean hospital LOS for patients from the five ICUs also decreased by 5.4% (14.7 vs. 13.9 days, p < 0.001). CONCLUSIONS: A multi-ICU, coordinated implementation of an early rehabilitation program markedly increased rehabilitation treatments in the ICU and was associated with reduced ICU and hospital LOS as well as increased ICU admissions.

Secondhand Smoking Is Associated With Vascular Inflammation.

BACKGROUND: The relative risk for cardiovascular diseases in passive smokers is similar to that of active smokers despite almost a 100-fold lower dose of inhaled cigarette smoke. However, the mechanisms underlying the surprising susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) have not been directly investigated. The aim of this study was to investigate directly vascular endothelial cell function in passive smokers. METHODS: Using a minimally invasive method of endothelial biopsy, we investigated directly the vascular endothelium in 23 healthy passive smokers, 25 healthy active smokers, and 23 healthy control subjects who had never smoked and had no regular exposure to SHS. Endothelial nitric oxide synthase (eNOS) function (expression of basal eNOS and activated eNOS [phosphorylated eNOS at serine1177 (P-eNOS)]) and expression of markers of inflammation (nuclear factor-κB [NF-κB]) and oxidative stress (nitrotyrosine) were assessed in freshly harvested venous endothelial cells by quantitative immunofluorescence. RESULTS: Expression of eNOS and P-eNOS was similarly reduced and expression of NF-κB was similarly increased in passive and active smokers compared with control subjects. Expression of nitrotyrosine was greater in active smokers than control subjects and similar in passive and active smokers. Brachial artery flow-mediated dilation was similarly reduced in passive and active smokers compared with control subjects, consistent with reduced endothelial NO bioavailability. CONCLUSIONS: Secondhand smoking increases vascular endothelial inflammation and reduces active eNOS to a similar extent as active cigarette smoking, indicating direct toxic effects of SHS on the vasculature.

Nocturnal non-invasive ventilation for cardio-respiratory disorders in adults.

Following the classic 'iron lung' non-invasive negative pressure ventilator, non-invasive positive pressure ventilation (NIPPV), particularly used 'nocturnally' has developed a broad role in both the acute hospital setting and domiciliary long-term use for many cardio-respiratory disorders associated with acute and chronic ventilatory failure. This role is based in part upon the perceived relative ease of application and discontinuation of NIPPV, ability to avoid intubation or tracheostomy and their associated morbidities and availability of increasingly portable pressure and volume cycled NIPPV devices. Nevertheless, the many methodologies necessary for optimal NIPPV use are often underappreciated by health care workers and patients alike. This review focuses on the rationale, practice, and future directions for 'nocturnal' use of non-invasive positive pressure ventilation (nNIV) in cardio-respiratory disorders in adults which are commonly associated with sleep-related apnea, hypoventilation and hypoxemia: congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), cystic fibrosis (CF) and neuromuscular disorders.

Impact of nonphysician staffing on outcomes in a medical ICU.

BACKGROUND: As the number of ICU beds and demand for intensivists increase, alternative solutions are needed to provide coverage for critically ill patients. The impact of different staffing models on the outcomes of patients in the medical ICU (MICU) remains unknown. In our study, we compare outcomes of nonphysician provider-based teams to those of medical house staff-based teams in the MICU. METHODS: We conducted a retrospective review of 590 daytime (7:00 am-7:00 pm) admissions to two MICUs at one hospital. In one MICU staffed by nurse practitioners and physician assistants (MICU-NP/PA) there were nonphysicians (nurse practitioners and physicians assistants) during the day (7:00 am-7:00 pm) with attending physician coverage overnight. In the other MICU, there were medicine residents (MICU-RES) (24 h/d). The outcomes investigated were hospital mortality, length of stay (LOS) (ICU, hospital), and posthospital discharge destination. RESULTS: Three hundred two patients were admitted to the MICU-NP/PA and 288 to the MICU-RES. Mortality probability model III (MPM(0)-III) predicted mortality was similar (P = .14). There was no significant difference in hospital mortality (32.1% for MICU-NP/PA vs 32.3% for MICU-RES, P = .96), MICU LOS (4.22 ± 2.51 days for MICU-NP/PA vs 4.44 ± 3.10 days for MICU-RES, P = .59), or hospital LOS (14.01 ± 2.92 days for MICU-NP/PA vs 13.74 ± 2.94 days for MICU-RES, P = .86). Discharge to a skilled care facility (vs home) was similar (37.1% for MICU-NP/PA vs 32.5% for MICU-RES, P = .34). After multivariate adjustment, MICU staffing type was not associated with hospital mortality (P = .26), MICU LOS (P = .29), hospital LOS (P = .19), or posthospital discharge destination (P = .90). CONCLUSIONS: Staffing models including daytime use of nonphysician providers appear to be a safe and effective alternative to the traditional house staff-based team in a high-acuity, adult ICU.

Gene expression profiles at diagnosis in de novo childhood AML patients identify FLT3 mutations with good clinical outcomes.

Fms-like tyrosine kinase 3 (FLT3) mutations are associated with unfavorable outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays to identify gene expression profiles related to FLT3 status and outcome in childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MUs), 24 with internal tandem duplications (ITDs) and 12 with activating loop mutations (ALMs). In addition, 8 of 19 specimens from patients with relapses had FLT3-MUs. Predictive analysis of microarrays (PAM) identified genes that differentiated FLT3-ITD from FLT3-ALM and FLT3 wild-type (FLT3-WT) cases. Among the 42 specimens with FLT3-MUs, PAM identified 128 genes that correlated with clinical outcome. Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45% versus 5% for those with an unfavorable signature (P = .018). Among FLT3-MU specimens, high expression of the RUNX3 gene and low expression of the ATRX gene were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was used to classify FLT3-MU cases into 3 EFS groups: 70%, 37%, and 0% for low, intermediate, and high ratios, respectively (P < .0001). Thus, gene expression profiling identified AML patients with divergent prognoses within the FLT3-MU group, and the RUNX3 to ATRX expression ratio should be a useful prognostic indicator in these patients.