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PurposeWith improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors’ posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes. Identification of outcome subtypes may advance understanding of post-ARDS morbidities.MethodsWe analysed baseline variables and 6-month health status for participants in the ARDS Network Long-Term Outcomes Study. After division into derivation and validation datasets, we used weighted network analysis to identify subtypes from predictors and outcomes in the derivation dataset. We then used recursive partitioning to develop a subtype classification rule and assessed adequacy of the classification rule using a kappa statistic with the validation dataset.ResultsAmong 645 ARDS survivors, 430 were in the derivation and 215 in the validation datasets. Physical and mental health status, but not cognitive status, were closely associated. Four distinct subtypes were apparent (percentages in the derivation cohort): (1) mildly impaired physical and mental health (22% of patients), (2) moderately impaired physical and mental health (39%), (3) severely impaired physical health with moderately impaired mental health (15%) and (4) severely impaired physical and mental health (24%). The classification rule had high agreement (kappa=0.89 in validation dataset). Female Latino smokers had the poorest status, while male, non-Latino non-smokers had the best status.ConclusionsWe identified four post-ARDS outcome subtypes that were predicted by sex, ethnicity, pre-ARDS smoking status and other baseline factors. These subtypes may help develop tailored rehabilitation strategies, including investigation of combined physical and mental health interventions, and distinct interventions to improve cognitive outcomes.

BackgroundWith improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding and improving quality of life (QOL) outcomes in ARDS survivors is a clinical and research priority. We sought to identify variables associated with QOL, as measured by the EQ-5D health utility score, after ARDS using contemporary data science methods.MethodsAnalysis of prospectively acquired baseline variables and 6-month EQ-5D health utility scores for adults with ARDS enrolled in the ARDS Network Long-Term Outcomes Study (ALTOS). Penalised regression identified predictors of health utility, with results validated using 10-fold cross-validation.ResultsAmong 616 ARDS survivors, several predictors were associated with 6-month EQ-5D utility scores, including two lifestyle factors. Specifically, older age, female sex, Hispanic/Latino ethnicity, current smoking and higher body mass index were associated with lower EQ-5D utilities, while living at home without assistance at baseline and AIDS were associated with higher EQ-5D utilities in ARDS survivors. No acute illness variables were associated with EQ-5D utility.ConclusionsAcute illness variables do not appear to be associated with postdischarge QOL among ARDS survivors. Functional independence and lifestyle factors, such as obesity and tobacco smoking, were associated with worse QOL. Future analyses of postdischarge health utility among ARDS survivors should incorporate measures of demographics and functional independence at baseline.Trial registration numbersNCT00719446 (ALTOS), NCT00434993 (ALTA), NCT00609180 (EDEN/OMEGA), and NCT00883948 (EDEN); Post-results.

Abstract Rationale Short-term follow-up in the Fluid and Catheter Treatment Trial (FACTT) suggested differential mortality by race with conservative fluid management, but no significant interaction. Objective In a post hoc analysis of FACTT including 1-year follow-up, we sought to estimate long-term mortality by race and test for an interaction between fluids and race. Methods We performed a post hoc analysis of FACTT and the Economic Analysis of Pulmonary Artery Catheters (EAPAC) study (which included 655 of the 1,000 FACTT patients with near-complete 1-year follow up). We fit a multistate Markov model to estimate 1-year mortality for all non-Hispanic black and white randomized FACTT subjects. The model estimated the distribution of time from randomization to hospital discharge or hospital death (available on all patients) and estimated the distribution of time from hospital discharge to death using data on patients after hospital discharge for patients in EAPAC. The 1-year mortality was found by combining these estimates. Results Non-Hispanic black (n = 217, 25%) or white identified subjects (n = 641, 75%) were included. There was a significant interaction between race and fluid treatment (P = 0.012). One-year mortality was lower for black subjects assigned to conservative fluids (38 vs. 54%; mean mortality difference, 16%; 95% confidence interval, 2–30%; P = 0.027 between conservative and liberal). Conversely, 1-year mortality for white subjects was 35% versus 30% for conservative versus liberal arms (mean mortality difference, −4.8%; 95% confidence interval, −13% to 3%; P = 0.23). Conclusions In our cohort, conservative fluid management may have improved 1-year mortality for non-Hispanic black patients with ARDS. However, we found no long-term benefit of conservative fluid management in white subjects.

PurposeSubphenotype classifiers for acute respiratory distress syndrome (ARDS) dichotomise patients into hyperinflammatory versus hypoinflammatory subgroups. These models demonstrated prognostic and predictive values but were developed primarily in Caucasian populations. Generalisability of these models in Asian patients, who experience worse clinical outcomes, has not been established. We aimed to profile host responses in Asian patients with ARDS and evaluate the generalisability of established classifiers in this understudied population compared with a Caucasian cohort.MethodsWe prospectively enrolled patients with ARDS from medical intensive care units in Beijing, China, and Pittsburgh, Pennsylvania, USA. In the Beijing cohort, 37 protein biomarkers were measured, with 10 overlapping biomarkers measured in the Pittsburgh cohort. Six established subphenotype models were assessed for generalisability and intermodel agreement. Sensitivity analyses, including latent class analysis, were conducted to explore biological heterogeneity within Asians.ResultsBetween 2011 and 2020, a total of 356 patients with ARDS (83% meeting the Berlin Definition; the rest on high-flow nasal cannula (HFNC) meeting the New Global Definition) were enrolled across Beijing (97% Han Asian) and Pittsburgh (90% Caucasian) sites, with comparable baseline hypoxaemia severity but disparate outcome. While the proportion of hyperinflammatory versus hypoinflammatory subphenotypes was predicted to be overall similar across different cohorts per each model, we observed poor intermodel agreement. We observed heightened inflammation in Berlin patients with ARDS compared with HFNC-ARDS within our Asian cohort.ConclusionEstablished subphenotype classifiers demonstrated similar distribution of subphenotypes in Asian patients with ARDS. However, poor intermodel agreement highlights the need for further investigation into model variability with models coming closer to bedside implementation.Trial registration numberNCT02975908.

Background Previous work has demonstrated a strong association between lung injury in African American children with pneumonia and a polymorphic (TG) m T n region in cystic fibrosis transmembrane conductance (CFTR) involved in the generation of a nonfunctional CFTR protein lacking exon 9. A number of splicing factors that regulate the inclusion/exclusion of exon 9 have been identified. The objective of this study was to determine whether genetic variants in these splicing factors were associated with acute respiratory distress syndrome (ARDS) in children with pneumonia. Methods This is a prospective cohort genetic association study of lung injury in African American and non-Hispanic Caucasian children with community-acquired pneumonia evaluated in the emergency department or admitted to the hospital. Linkage-disequilibrium-tag single nucleotide polymorphisms (LD-tag SNPs) in genes of the following splicing factors (followed by gene name) involved in exon 9 skipping PTB1 ( PTBP1 ), SRp40 ( SFRS1 ), SR2/ASF ( SFRS5 ), TDP-43 ( TARDBP ), TIA-1 ( TIA1 ), and U2AF 65 ( U2AF2 ) were genotyped. SNPs in the gene of the splicing factor CELF2 ( CELF2 ) were selected by conservation score. Multivariable analysis was used to examine association between genotypes and ARDS. Results The African American cohort ( n  = 474) had 29 children with ARDS and the non-Hispanic Caucasian cohort ( n  = 304) had 32 children with ARDS. In the African American group multivariable analysis indicated that three variants in CELF2 , rs7068124 ( p  = 0.004), rs3814634 ( p  = 0.032) and rs10905928 ( p  = 0.044), and two in TIA1 , rs2592178 ( p  = 0.005) and rs13402990 ( p  = 0.018) were independently associated with ARDS. In the non-Hispanic Caucasian group, a single variant in CELF2 , rs2277212 ( p  = 0.014), was associated with increased risk of developing ARDS. Conclusions The data indicate that SNPs in CELF2 may be associated with the risk of developing ARDS in both African American and non-Hispanic Caucasian children with pneumonia and suggest that the potential role of the splicing factor CELF2 in ARDS should be explored further.

Objective: To determine whether race/ethnicity and sex independently increase risk of respiratory distress syndrome (RDS) in late preterm and term infants. Study Design: Using a cohort design, we studied the risk of RDS associated with race/ethnicity and sex in infants with gestational age (GA) 34 to 42 weeks born between 1 January 2000 and 31 December 2009 ( n =286 454) within 12 hospitals in the Northern California Kaiser Permanente Medical Care Program. Result: Male sex (adjusted odds ratio (aOR) 1.68; 95% confidence interval 1.45 to 1.93) and White race/ethnicity (vs Asians (aOR 0.57; 95% confidence interval 0.47 to 0.70), Blacks (aOR 0.66; 95% confidence interval 0.50 to 0.87), and Hispanics (aOR 0.76; 95% confidence interval 0.64 to 0.90)) independently increase risk for RDS regardless of GA. A GA <39 weeks, operative delivery, maternal diabetes, and chorioamnionitis also increased RDS risk in this cohort. Conclusion: Male sex and White race/ethnicity independently increase risk for RDS in late preterm and term infants. Timing of elective delivery should acknowledge these risks.

Keywords: Migrants, Borrelia recurrentis, Leptospira, Borreliosis, Leptospirosis

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are sequelae of severe trauma. It is unknown if certain races are at greater risk of developing ALI/ARDS, and once established, if there are racial differences in the severity of lung injury or mortality. Retrospective cohort study of 4,397 trauma patients (1,831 Caucasians, 871 African-Americans, 886 Hispanics, and 809 Asian/Pacific Islanders) requiring intensive care unit (ICU) admission between 1996 and 2007 at an urban Level I trauma center. African-American patients were most likely to present in shock with penetrating trauma and receive a massive transfusion. The incidence of ALI/ARDS was similar by race ( P = .99). Among patients who developed ALI/ARDS, there was no evidence to support a difference in partial pressure of oxygen in arterial blood to fraction of inspired oxygen (Pa o 2/Fi o 2) ( P = .33), lung injury score ( P = .67), or mortality ( P = .78) by race. Despite differences in baseline characteristics, the incidence of ALI/ARDS, severity of lung injury, and mortality were similar by race.

The annual incidences of severe sepsis in several industrialized nations have recently been reported to be 50–100 cases per 100,000 persons. These numbers exceed the estimated rates for other diseases that hold a heightened public awareness, including breast cancer and acquired immune deficiency syndrome. There are also sex and race differences in the incidence of sepsis. Men are more likely than women to develop sepsis, with a mean annual relative risk of 1.28. Nonwhites are nearly twice as likely to develop sepsis as whites. These race and sex disparities in the incidence of sepsis are likely explained by differences in a variety of factors, including the presence of comorbid conditions. For example, chronic alcohol abuse is associated with a persistent fever, delayed resolution of symptoms, increased rates of bacteremia, increased use of intensive care, prolonged duration of hospital stay, and increased cost of hospitalization for infected patients.

Background:In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified.Methods:Because Yakuts are considered as a population isolate and the disease is rare in other populations, genomewide homozygosity mapping was performed using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut.Results:All families shared an identical haplotype in the same region as the identical loci responsible for 3-M and gloomy face syndromes and a novel homozygous 4582insT mutation in Cullin 7 (CUL7) was found, which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 (Q1553X). Yakut patients with short stature syndrome have unique features such as a high frequency of neonatal respiratory distress and few bone abnormalities, whereas the clinical features of the other Yakut patients were similar to those of 3-M syndrome. Furthermore, abnormal vascularisation was present in the fetal placenta and an abnormal development of cartilage tissue in the bronchus of a fetus with CUL7 mutation.Conclusion:These findings may provide a new understanding of the clinical diversity and pathogenesis of short stature syndrome with CUL7 mutation.