Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

Predicting the Length of Mechanical Ventilation in Acute Respiratory Disease Syndrome Using Machine Learning: The PIONEER Study.

Background: The ability to predict a long duration of mechanical ventilation (MV) by clinicians is very limited. We assessed the value of machine learning (ML) for early prediction of the duration of MV > 14 days in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This is a development, testing, and external validation study using data from 1173 patients on MV ≥ 3 days with moderate-to-severe ARDS. We first developed and tested prediction models in 920 ARDS patients using relevant features captured at the time of moderate/severe ARDS diagnosis, at 24 h and 72 h after diagnosis with logistic regression, and Multilayer Perceptron, Support Vector Machine, and Random Forest ML techniques. For external validation, we used an independent cohort of 253 patients on MV ≥ 3 days with moderate/severe ARDS. Results: A total of 441 patients (48%) from the derivation cohort (n = 920) and 100 patients (40%) from the validation cohort (n = 253) were mechanically ventilated for >14 days [median 14 days (IQR 8-25) vs. 13 days (IQR 7-21), respectively]. The best early prediction model was obtained with data collected at 72 h after moderate/severe ARDS diagnosis. Multilayer Perceptron risk modeling identified major prognostic factors for the duration of MV > 14 days, including PaO2/FiO2, PaCO2, pH, and positive end-expiratory pressure. Predictions of the duration of MV > 14 days showed modest discrimination [AUC 0.71 (95%CI 0.65-0.76)]. Conclusions: Prolonged MV duration in moderate/severe ARDS patients remains difficult to predict early even with ML techniques such as Multilayer Perceptron and using data at 72 h of diagnosis. More research is needed to identify markers for predicting the length of MV. This study was registered on 14 August 2023 at ClinicalTrials.gov (NCT NCT05993377).

DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study.

BACKGROUND: Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients. METHODS: PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias. RESULTS: Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation. CONCLUSION: Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.

Bilateral internal thoracic artery versus single internal thoracic artery plus radial artery: A double meta-analytic approach.

OBJECTIVES: We explored the current evidence on the best second conduit in coronary surgery carrying out a double meta-analysis of propensity score matched or adjusted studies comparing bilateral internal thoracic artery (BITA) versus single internal thoracic artery plus radial artery. METHODS: PubMed, Embase, and Google Scholar were searched for propensity score matched or adjusted studies comparing BITA versus single internal thoracic artery plus radial artery. The end point was long-term mortality. Two statistical approaches were used: the generic inverse variance method and the pooled meta-analysis of Kaplan-Meier-derived individual patient data. RESULTS: Twelve matched populations comparing 6450 patients with BITA versus 9428 patients with single internal thoracic artery plus radial artery were included in our meta-analysis. The generic inverse variance method showed a statistically significant survival benefit of the BITA group (hazard ratio, 0.84; 95% CI, 0.74-0.95; P = .04). The Kaplan-Meier estimates of survival at 1, 5, 10, and 15 years of the BITA group were 97.0%, 91.3%, 80.0%, and 68.0%, respectively. The Kaplan-Meier estimates of survival at 1, 5, 10, and 15 years of the single internal thoracic artery plus radial artery group were 97.3%, 91.5%, 79.9%, and 63.9%, respectively. The Kaplan-Meier-derived individual patient data meta-analysis applied to very long follow-up time data, showed that BITA provided a survival benefit after 10 years from surgery (hazard ratio, 0.77; 95% CI, 0.63-0.94; P = .01). No differences in terms of survival between the 2 groups were detected when the analysis was focused on the first 10 years of follow-up (hazard ratio, 0.99; 95% CI, 0.91-1.09; P = .93). CONCLUSIONS: The present meta-analysis suggests that double internal thoracic artery may provide, compared with single internal thoracic artery plus radial artery, a statistically significant survival advantage after 10 years of follow-up, but not before. VIDEO ABSTRACT.

An Artificial Intelligence Prediction Model of Insulin Sensitivity, Insulin Resistance, and Diabetes Using Genes Obtained through Differential Expression.

Insulin is a powerful pleiotropic hormone that affects processes such as cell growth, energy expenditure, and carbohydrate, lipid, and protein metabolism. The molecular mechanisms by which insulin regulates muscle metabolism and the underlying defects that cause insulin resistance have not been fully elucidated. This study aimed to perform a microarray data analysis to find differentially expressed genes. The analysis has been based on the data of a study deposited in Gene Expression Omnibus (GEO) with the identifier "GSE22309". The selected data contain samples from three types of patients after taking insulin treatment: patients with diabetes (DB), patients with insulin sensitivity (IS), and patients with insulin resistance (IR). Through an analysis of omics data, 20 genes were found to be differentially expressed (DEG) between the three possible comparisons obtained (DB vs. IS, DB vs. IR, and IS vs. IR); these data sets have been used to develop predictive models through machine learning (ML) techniques to classify patients with respect to the three categories mentioned previously. All the ML techniques present an accuracy superior to 80%, reaching almost 90% when unifying IR and DB categories.

Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.

Prediction of major bleeding events in 1381 patients with essential thrombocythemia.

The goal of therapy in essential thrombocythemia (ET) is reducing thrombotic risk. No algorithm to predict hemorrhage risk exists. The impact ofanti-platelet, cytoreductive and anticoagulation therapies on risk of major bleeding (MB) was evaluated. MB events were retrospectively analyzed in 1381 ET from 10 European centers. There were 0.286 MB events/person-year. Neither the International Thrombosis Prognostic Score for thrombosis in essential thrombocythemia (IPSET-t) nor the revised IPSET-t (r-IPSET-t) was predictive for hemorrhage-free survival at 10 years (p = 0.092 vs p = 0.1). Ageand leukocyte count were MB risk factors, while low hemoglobin was protective. For ET with extreme thrombocytosis (ExtT) and leukocytosis cytoreduction was not protective. MB were more frequent in ET with ExtT who received anticoagulation. Antiplatelet therapy was not, while anticoagulation was a risk factor for MB (HR 3.05, p = 0.016, CI 1.23-7.56), in particular vitamin K antagonists (22.6% of those treated had a MB event, HR 2.96, p = 0.004, CI 1.41-6.22). Survival at 10 years was associated with hemorrhage (OR 2.54, p < 0.001) but not thrombosis (HR 0.95, p = 0.829). Hemorrhage has a higher risk of mortality than thrombosis. Improved risk stratification for MB is necessary. The choice of anticoagulation, cytoreduction and antiplatelet therapies is an important area of research in ET.

Predicting ICU Mortality in Acute Respiratory Distress Syndrome Patients Using Machine Learning: The Predicting Outcome and STratifiCation of severity in ARDS (POSTCARDS) Study.

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pa o2 /F io2 , inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82-0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87-0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period: The multinational randomized LeoDOR trial.

AIM: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). METHODS AND RESULTS: In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 µg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 µg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12-7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87-3.11; p = 0.122). CONCLUSIONS: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability.

25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis.

The role of Vitamin D in the development of type 1 diabetes (T1D) is controversial. The Canary Islands have the highest incidence of childhood-onset T1D in Spain and one of the highest in Europe. We aimed to evaluate 25OHVitamin D concentrations in a Canarian pediatric population, to assess the existence of seasonal variation, to study their association with T1D, and to evaluate the role of acidosis in its levels. In a retrospective, case-control study, we obtained data from 146 T1D patients (<15 years of age) and 346 control children; 25OHVitamin D concentrations were assessed in serum by automatic ChemiLuminescence ImmunoAssay technology. We found significantly higher 25OHVitamin D levels in the summer and autumn months and an inverse correlation between T1D and age; 25OHVitamin D sufficiency was similar in both groups (44.5% vs. 45.1%), with significant differences in the percentage of patients presenting vitamin D deficiency (11.6% (T1D) vs. 16.4% (controls)). When stratified according to the presence of ketoacidosis at sampling, only patients with acidosis showed lower 25OHVitamin D concentrations than controls. Despite its subtropical geographic location, Vitamin D deficiency is frequent in children in Gran Canaria, and 25OHVitamin D concentrations show seasonal variation. After adjusting for acidosis, no differences were found between children with and without T1D.

The Healthy Lifestyle Habits Screening Questionnaire: A pilot study in the Canary Islands.

OBJECTIVE: This study aimed to assess the validity and reliability of a self-administered screening questionnaire to detect deficiencies in the health habits of the adult population of the Canary Islands (Spain). DESIGN: The questionnaire initially included 30 items based on previous questionnaires and following the recommendations of the World Health Organization about healthy and unhealthy diet, screen time, physical activity, and sleep habits. It also included a section related to hygiene due to the importance that hygienic habits have in people's health. SETTING: The questionnaire was self-administered online. PARTICIPANTS: Data was collected from 401 participants from the Canary Islands (age range: 18-73 years) who volunteered to fill in the questionnaire online. RESULTS: The questionnaire revealed adequate overall reliability indexes (Cronbach's α>.70, Mcdonald's ω>.70), and construct validity. Hierarchical linear regression analysis revealed age, sex, and income to be significantly (p<.05) related to adults' health lifestyle habits in our population, sex and age explaining the majority of the variance. However, education and incomes were found non-significant (p>.05) when education was introduced into the model. Those results pointed out that older people and women show healthier lifestyle habits. CONCLUSION: The questionnaire proved to be a brief, reliable, and valid tool to assess health lifestyle habits in adults in the Canary Islands. Furthermore, results pointed out that in future intervention studies with children, variables such as adults' sex, age, and, to a lesser extent, monthly income should be taken into consideration.

Depression and anxiety in systemic lupus erythematosus: A case-control study on prevalence and associated factors in a single-center cohort.

OBJECTIVES: To evaluate the prevalence of self-perceived depression and anxiety in patients with systemic lupus erythematosus (SLE) and to explore associated factors. METHODS: Cross-sectional study of unselected patients with SLE (ACR-97 criteria) and controls with chronic inflammatory rheumatic diseases. Both completed the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical characteristics, comorbidity, and treatments were collected, and a multivariate analysis was performed to explore factors associated with depression and anxiety in SLE. RESULTS: The study population comprised 172 patients and 215 controls. Women accounted for 93% of the patients with SLE. Fibromyalgia was recorded in 12.8% and a history of depression in 17%. According to HADS, 37.2% fulfilled the diagnostic criteria for depression and 58.7% those for anxiety; prevalence was similar in the controls (32.6% and 55.1%, respectively). Up to a third of patients with self-perceived depression were not receiving antidepressants. There was no concordance between a previous history of depression and current depression. In the multivariate model, current depression was associated with single marital status (OR 2.69; 95% CI: 1.17-6.42; p = .022), fibromyalgia (7.69; 2.35-30.72; p = .001), smoking (3.12; 1.24-8.07; p = .016), severity of SLE (0.76; 0.6-0.94; p = .016), and organ damage (1.27; 1.01-1.61; p = .042). Current anxiety was only associated with fibromyalgia (3.97; 1.21-17.98; p = .036). CONCLUSIONS: Depression and anxiety are most likely underdiagnosed in SLE. Prevalence appears to be similar to that of other chronic inflammatory rheumatic diseases. Anxiety is associated with fibromyalgia, while depression is also associated with single marital status, smoking, organ damage, and severity of SLE.

Coronary surgery provides better survival than drug-eluting stent: A pooled meta-analysis of Kaplan- Meier-derived individual patient data.

OBJECTIVES: We explored the current evidence on coronary disease treatment comparing the survival of 2 therapeutic strategies: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stent (DES). METHODS: PubMed, Embase, and Google Scholar were searched for randomized clinical trials comparing CABG versus PCI with DES. The end point was overall mortality. Two statistical approaches were used: the generic inverse variance method, which was used to pool the incident rate ratios, and the pooled meta-analysis of Kaplan-Meier-derived individual patient data. RESULTS: Eight randomized clinical trials comparing 4975 patients undergoing CABG and 4992 patients undergoing PCI were included in our meta-analysis. Generic inverse variance method showed a statistically significant survival benefit of the CABG group (incident rate ratio, 1.21; 95% confidence interval, 1.09-1.35; P < .01). The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the CABG group were 97.1%, 90.3%, and 80.3%, respectively. The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the PCI group were 97.0%, 87.7%, and 76.4%, respectively. The log-rank analysis confirmed a statistically significant benefit in term of overall mortality of the CABG group (hazard ratio, 1.24; 95% confidence interval, 1.11-1.38; P = .0001). CONCLUSIONS: The present meta-analysis suggests that CABG provides a consistent survival benefit over PCI with DES.

Effect of Conventional Cataract Surgery and Femtosecond Laser-Assisted Cataract Surgery on Bruch's Membrane Opening-Minimum Rim Width, Retinal Nerve Fiber Layer, and Macular Thickness.

Purpose: To evaluate the effect of conventional cataract surgery (CCS) and femtosecond laser-assisted cataract surgery (FLACS) on Bruch's membrane opening-minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFL), and macular thickness (MT) using spectral-domain optical coherence tomography (SD-OCT). Methods: BMO-MRW, RNFL, and MT were measured using SD-OCT preoperatively, 1 month and 6 months after surgery in both CCS and FLACS groups. Differences between preoperative and postoperative values were evaluated in both groups. The postoperative changes were evaluated in each group and compared between groups. Results: A total of 146 eyes of 146 patients were included in this study, 65 underwent CCS, and 81 underwent FLACS. One month after surgery, there was an increase (in microns) of 20.93 in BMO-MRW, 4.26 in RNFL, and 7.85 in MT in CCS group (P < 0.001), and 17.7, 3.73, and 5.65, respectively, in FLACS group (P < 0.001). Six months after surgery, there was an increase of 12.53 in BMO-MRW, 1.42 in RNFL, and 4.72 in MT in CCS group (P < 0.001), and 13.7, 1.88, and 4.14, respectively, in FLACS group (P < 0.001). The postoperative changes in CCS group were similar to those in FLACS group. Conclusion: CCS as well as FLACS result in a slight increase in BMO-MRW, RNFL, and MT values one month and six months after surgery. Neither CCS nor FLACS lead to a deterioration in the parameters that define the structure of the optic nerve head and the macula. These results suggest that FLACS is as safe as CCS regarding the optic nerve head and the macula in normal eyes.

Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome.

Mortality is a frequently reported outcome in clinical studies of acute respiratory distress syndrome (ARDS). However, timing of mortality assessment has not been well characterized. We aimed to identify a crossing-point between cumulative survival and death in the intensive care unit (ICU) of patients with moderate-to-severe ARDS, beyond which the number of survivors would exceed the number of deaths. We hypothesized that this intersection would occur earlier in a successful clinical trial vs. observational studies of moderate/severe ARDS and predict treatment response. We conducted an ancillary study of 1580 patients with moderate-to-severe ARDS managed with lung-protective ventilation to assess the relevance and timing of measuring ICU mortality rates at different time-points during ICU stay. First, we analyzed 1303 patients from four multicenter, observational cohorts enrolling consecutive patients with moderate/severe ARDS. We assessed cumulative ICU survival from the time of moderate/severe ARDS diagnosis to ventilatory support discontinuation within 7-days, 28-days, 60-days, and at ICU discharge. Then, we compared these findings to those of a successful randomized trial of 277 moderate/severe ARDS patients. In the observational cohorts, ICU mortality (487/1303, 37.4%) and 28-day mortality (425/1102, 38.6%) were similar (p = 0.549). Cumulative proportion of ICU survivors and non-survivors crossed at day-7; after day-7, the number of ICU survivors was progressively higher compared to non-survivors. Measures of oxygenation, lung mechanics, and severity scores were different between survivors and non-survivors at each point-in-time (p < 0.001). In the trial cohort, the cumulative proportion of survivors and non-survivors in the treatment group crossed before day-3 after diagnosis of moderate/severe ARDS. In clinical ARDS studies, 28-day mortality closely approximates and may be used as a surrogate for ICU mortality. For patients with moderate-to-severe ARDS, ICU mortality assessment within the first week of a trial might be an early predictor of treatment response.

Respiratory Subsets in Patients with Moderate to Severe Acute Respiratory Distress Syndrome for Early Prediction of Death.

Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO2 ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO2/FiO2 threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO2/FiO2 (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H2O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO2 approach: (I) PaO2/FiO2 ≥ 150 at PEEP < 10, (II) PaO2/FiO2 ≥ 150 at PEEP ≥ 10, (III) PaO2/FiO2 < 150 at PEEP < 10, and (IV) PaO2/FiO2 < 150 at PEEP ≥ 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO2/FiO2 < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO2/FiO2 < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO2/FiO2 ≥ 150 (hazard ratio 2.8, 95% CI 2.2−3.5, p < 0.0001). Conclusions: Subsets based on PaO2/FiO2 thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials.