Outcomes of Acute Respiratory Failure in Patients With Cancer in the United States.

OBJECTIVE: To determine the epidemiological effect-magnitude and outcomes of patients with cancer vs those without cancer who are hospitalized with acute respiratory failure (ARF). PATIENTS AND METHODS: We reviewed hospitalizations within the National Inpatient Sample (NIS) database between January 1, 2016, and December 31, 2018. Patients were classified based on a diagnosis of solid-organ cancer, hematologic cancer, or no cancer. Noninvasive positive pressure ventilation (NIPPV) failure was defined as patients who initially received NIPPV and had progression to invasive mechanical ventilation. Weighted samples were used to derive population estimates. RESULTS: During the study period, there were an estimated 8,837,209 admissions with ARF in the United States, 8.9% (783,625) of which had solid-organ cancer and 2.0% (176,095) had hematologic cancers. Annually, 319,907 patients with cancer are admitted with ARF, with 27.3% (87,302) requiring invasive mechanical ventilation and 10.0% (31,998) requiring NIPPV. In-hospital mortality was higher in patients with cancer vs those without cancer (24.0% [76,813] vs 12.3% [322,465]; P<.001), and this proprotion persisted when stratified by the highest method of oxygen delivery. Patients with cancer had longer hospital length of stay (7.0 days [3.0 to 12.0 days] vs 5.0 days [3.0 to 10.0 days]; P<.001) and were more likely to have NIPPV failure (14.9% [3,992] vs 12.8% [41,875]). Compared with those with solid-organ cancer, patients with hematologic cancers experienced worse outcomes. The association between underlying cancer diagnosis and outcomes remained consistent when adjusted for age, sex, and comorbidities. CONCLUSION: In the United States, patients with cancer account for over 10% of ARF hospital admissions (959,720 of 8,837,209). They experience an approximately 2-fold higher mortality versus those without cancer. Those with hematologic cancers appear to experience worse outcomes than patients with solid-organ cancers.

Pulmonary function as a continuum of risk: critical care utilization and survival after allogeneic hematopoietic stem cell transplantation - a multicenter cohort study.

Abnormal pre-transplant pulmonary function tests (PFTs) are associated with reduced survival after allogeneic HCT. Existing scoring systems consider risk dichotomously, attributing risk only to those with abnormal lung function. In a multicenter cohort of 1717 allo-HCT recipients, we examined the association between pre-transplant PFT measures and need for ICU admission (120d), frequency of mechanical ventilation (120d) and overall survival (5 y). Predictive models were developed and validated using Cox proportional hazards, incorporating age, FEV1 (forced expiratory volume in 1-second) and diffusing capacity (DLCO). In univariate analysis, hazard ratios for each outcome (95% CI) were: mechanical ventilation (FEV1: 0.60 [0.52-0.69], DLCO: 0.69 [0.61-0.77], p < 0.001), ICU admission (FEV1: 0.74 [0.67-0.82], DLCO: 0.79 [0.72-0.86], p < 0.001) and overall survival (FEV1: HR 0.87 [0.81-0.94], DLCO: 0.83 [0.77-0.89], p < 0.001). A multivariable Cox model was developed and compared to the HCT-CI Pulmonary score in a validation cohort. This model was better at predicting need for ICU admission and mechanical ventilation, while both models predicted overall survival (p < 0.001). In conclusion, the risk conferred by pre-transplant pulmonary function should be considered in a continuous rather than dichotomous manner. A more granular prognostication system can better inform risk of critical care utilization in the early post-HCT period.

Temporal trends in critical care utilization and outcomes in allogeneic hematopoietic stem cell transplant recipients.

Historically, the prognosis of allogeneic hematopoietic stem cell transplant (allo-HCT) recipients who require intensive care unit (ICU) admission has been poor. We aimed to describe the epidemiological trends of ICU utilization and outcomes in allo-HCT patients. We conducted a retrospective cohort study including adults (≥ 18) undergoing allo-HCT between 01/01/2005 and 31/12/2020 at Mayo Clinic, Rochester. Temporal trends in outcomes were assessed by robust linear regression modelling. Risk factors for hospital mortality were chosen a priori and assessed with multivariable logistic regression modelling. Of 1,249 subjects, there were 486 ICU admissions among 287 individuals. Although older patients underwent allo-HCT (1.64 [95% CI: 1.11 to 2.45] years per year; P = 0.025), there was no change in ICU utilization over time (P = 0.91). The ICU and hospital mortality rates were 19.2% (55/287) and 28.2% (81/287), respectively. There was a decline in ICU mortality (-0.38% [95% CI: -0.70 to -0.06%] per year; P = 0.035). The 1-year post-HCT mortality for those requiring ICU admission was 56.1% (161/287), with no significant difference over time, versus 15.8% (141/891, 71 missing) among those who did not. The frequency and duration of invasive mechanical ventilation (IMV) declined. In multivariable analyses, higher serum lactate, higher sequential organ failure assessment (SOFA) scores, acute respiratory distress (ARDS), and need for IMV were associated with greater odds of hospital mortality. Over time, rates of ICU utilization have remained stable, despite increasing patient age. Several trends suggest improvement in outcomes, notably lower ICU mortality and frequency of IMV. However, long-term survival remains unchanged. Further work is needed to improve long-term outcomes in this population.

Adjusting diffusing capacity for anemia in patients undergoing allogeneic HCT: a comparison of two methodologies.

BACKGROUND: Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint. STUDY DESIGN: This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis. RESULTS: Patients had normal spirometry (FEV1 99.7% [IQR: 89.4-109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9-94.1%) while Dinakara-DLCO 111.0% (97.3-124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV1, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20). CONCLUSION: The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.

Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Early machine learning prediction of hospitalized patients at low risk of respiratory deterioration or mortality in community-acquired pneumonia: Derivation and validation of a multivariable model.

Current prognostic tools for pneumonia predominantly focus on mortality, often neglecting other crucial outcomes such as the need for advanced respiratory support. The objective of this study was to develop and validate a tool that predicts the early risk of non-occurrence of respiratory deterioration or mortality. We conducted a single-center, retrospective cohort study involving hospitalized adult patients with community-acquired pneumonia (CAP) and acute hypoxic respiratory failure from January 2009 to December 2019 (n = 4379). We employed the gradient boosting machine (GBM) learning to create a model that estimates the likelihood of patients requiring advanced respiratory support (high flow nasal cannula [HFNC], non-invasive mechanical ventilation [NIMV], and invasive mechanical ventilation [IMV]) or facing mortality during hospitalization. This model utilized readily available data including demographic, physiologic, and laboratory data, sourced from electronic health records and obtained within the first six hours of admission. Out of the cohort, 890 patients (25.2%) either required advanced respiratory support or died during their hospital stay. Our predictive model displayed superior discrimination and higher sensitivity (cross-validation C-statistic = 0.71; specificity = 0.56; sensitivity = 0.72) compared to the pneumonia severity index (PSI) (C-statistic = 0.65; specificity = 0.91; sensitivity = 0.24; P value < 0.001), while maintaining a negative predictive value (NPV) of approximately 0.85. These data demonstrate that our machine learning model predicted the non-occurrence of respiratory deterioration or mortality among hospitalized CAP patients more accurately than the PSI. The enhanced sensitivity of this model holds potential for reliably excluding low-risk patients from pneumonia clinical trials.

Accommodating Bereaved Parents in the Workplace: A Scoping Review.

Helpful workplace support strategies and accommodations (WSSA) for bereaved parents returning to work was assessed via comprehensive search of databases from 1990-1/21/22. 11 of 45 qualitative articles met inclusion. Bereaved parents often felt returning to work provided a coping strategy for and/or distraction from grief; however, some received insensitive comments by employer/coworkers. Helpful WSSA included flexibility on date to return to work and schedule. In conclusion, due to the intensity of their grief, bereaved parents benefit from a workplace offering individualized time off for bereavement & workplace accommodations to address potential difficulty meeting prior productivity demands.

Prognostic Significance of Early Declines in Pulmonary Function After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Pulmonary function test (PFT) impairments are common after allogeneic hematopoietic stem cell transplantation. The prognostic significance of these declines on outcomes is not well understood.The objectives were to determine the frequency of declines in pulmonary function (FVC, FEV1, and diffusing capacity for carbon monoxide [DLCO]) in the early post-transplantation period; and to determine the prognostic significance of these declines on mortality or development of bronchiolitis obliterans syndrome. METHODS: This was a retrospective cohort study conducted at Mayo Clinic, Rochester, Minnesota. PFTs were obtained at baseline and at day +100. Competing risk survival models were developed, which accounted for pre-transplantation pulmonary function and relapse status. RESULTS: Between January 1, 2005, and December 31, 2020, 1,145 subjects underwent allogeneic hematopoietic stem cell transplantation and had a pre-transplantation PFT performed. Of these, 900 (78.6%) survived to day 100 and had post-transplantation PFTs performed (median [interquartile range] 97 [94-103] d). A decline of ≥10% in FEV1, FVC, or DLCO was seen in 401 of 900 subjects (44.5%). Declines of ≥20% in FEV1 (hazard ratio 1.65, 95% CI 1.07-2.56; P = .02), FVC (hazard ratio 1.72, 95% CI [1.11-2.67]; P = .02), and DLCO (hazard ratio 1.46, 95% CI 1.04-2.07; P = .028) were all associated with reduced survival when compared with those with < 10% decline in PFT measures. These findings were independent of pre-transplantation pulmonary function or relapse status. Bronchiolitis obliterans syndrome was diagnosed in 118 subjects (10.3%), and there was no relationship between early PFT decline and a subsequent diagnosis of bronchiolitis obliterans syndrome. The subjects who received myeloablative conditioning with cyclophosphamide plus total body irradiation or cyclophosphamide plus fludarabine plus total body irradiation were more likely to have lower spirometry values after hematopoietic stem cell transplantation. The subjects who received reduced intensity conditioning or nonmyeloablative conditioning with fludarabine plus total body irradiation were more likely to have higher post-hematopoietic stem cell transplantation FEV1, FVC, and DLCO. CONCLUSIONS: An absolute decline of ≥20% in FEV1, FVC, or DLCO were associated with reduced survival independent of pre-transplantation pulmonary function or relapse status. In contrast to previous work, early declines in PFT measures were not associated with future development of bronchiolitis obliterans syndrome.

Development and Validation of an Acute Respiratory Distress Syndrome Prediction Model in Coronavirus Disease 2019: Updated Lung Injury Prediction Score.

OBJECTIVE: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19. PATIENTS AND METHODS: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale. RESULTS: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively. CONCLUSION: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

BACKGROUND: ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. METHODS: This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. RESULTS: One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13-3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91-0.99], P = .02), lower bicarbonate (OR 0.94 [0.88-0.99], P = .035), and higher creatinine (OR 1.91 [1.23-2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48-3.94], P < .001), opioids (OR 2.94 [1.67-5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30-1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34-2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33-1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2-301.7], P < .001), bloodstream infection (OR 4.59 [2.46-8.57], P < .001), and pneumonia (OR 9.76 [5.01-19.00], P < .001). CONCLUSIONS: Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Early, biomarker-guided steroid dosing in COVID-19 Pneumonia: a pilot randomized controlled trial.

ClinicalTrials.gov identifier (NCT number): NCT03852537 , Registered February 25, 2019.

Characterization of Platelet Biologic Markers in the Early Pathogenesis of Postoperative Acute Respiratory Distress Syndrome.

Animal models and limited human studies have suggested a plausible role for platelets in the pathogenesis and resolution of acute respiratory distress syndrome (ARDS). However, there are little data regarding the role of platelets in ARDS development. OBJECTIVES: The objective of this study was to characterize the role of platelets in a postoperative ARDS model through an analysis of two platelet-specific biologic markers: thromboxane A2 (TxA2) and soluble CD-40-ligand (sCD40L). DESIGN SETTING AND PARTICIPANTS: This was a nested case-control study of ARDS cases matched to non-ARDS controls. Blood samples were collected from a cohort of 500 patients undergoing thoracic, aortic vascular, or cardiac surgery that placed them at high-risk of developing postoperative ARDS. MAIN OUTCOMES AND MEASURES: TxA2 and sCD40L were analyzed at baseline (prior to surgical incision) as well as 2 hours and 6 hours after the key intraoperative events believed to be associated with increased risk of postoperative ARDS. RESULTS: Of 500 patients enrolled, 20 ARDS cases were matched 1:2 to non-ARDS controls based on age, sex, surgical procedure, and surgical lung injury prediction score. Those who developed ARDS had longer surgeries, greater fluid administration, and higher peak inspiratory pressures. There were no significant differences in levels of TxA2 or sCD40L at baseline, at 2 hours, or at 6 hours. There was also no difference in the change in biomarker concentration between baseline and 2 hours or baseline and 6 hours. CONCLUSIONS: Two novel platelet-associated biologic markers (TxA2 and sCD40L) were not elevated in patients who developed ARDS in a postoperative ARDS model. Although limited by the relatively small study size, these results do not support a clear role for platelets in the early pathogenesis of postoperative ARDS.

CNS Demyelinating Attacks Requiring Ventilatory Support With Myelin Oligodendrocyte Glycoprotein or Aquaporin-4 Antibodies.

BACKGROUND AND OBJECTIVE: Severe attacks of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) may require ventilatory support, but data on episodes are limited, particularly for MOGAD. We sought to compare the frequency, characteristics, and outcomes of MOGAD and AQP4-NMOSD attacks requiring ventilatory support. METHODS: This retrospective descriptive study identified Mayo Clinic patients (January 1, 1996-December 1, 2020) with MOGAD or AQP4-NMOSD and an attack requiring noninvasive or invasive ventilation at Mayo Clinic or an outside facility by searching for relevant terms in their electronic medical record. Inclusion criteria were (1) attack-related requirement for noninvasive (bilevel positive airway pressure or continuous positive airway pressure) or invasive respiratory support (mechanical ventilation); (2) MOG or AQP4 antibody positivity with fulfillment of MOGAD and AQP4-NMOSD clinical diagnostic criteria, respectively; and (3) sufficient clinical details. We collected data on demographics, comorbid conditions, indication for and duration of respiratory support, MRI findings, treatments, and outcomes. The races of those with attacks requiring respiratory support were compared to those without such attacks in MOGAD and AQP4-NMOSD. RESULTS: Attacks requiring ventilatory support were similarly rare in patients with MOGAD (8 of 279, 2.9%) and AQP4-NMOSD (11 of 503 [2.2%]) (p = 0.63). The age at attack (median years [range]) (MOGAD 31.5 [5-47] vs AQP4-NMOSD 43 [14-65]; p = 0.01) and percentage of female sex (MOGAD 3 of 8 [38%] vs AQP4-NMOSD 10 of 11 [91%]; p = 0.04) differed. The reasons for ventilation differed between MOGAD (inability to protect airway from seizure, encephalitis or encephalomyelitis with attacks of acute disseminated encephalomyelitis 5 [62.5%] or unilateral cortical encephalitis 3 [37.5%]) and AQP4-NMOSD (inability to protect airway from cervical myelitis 9 [82%], rhombencephalitis 1 [9%], or combinations of both 1 [9%]). Median ventilation duration for MOGAD was 2 days (range 1-7 days) vs 19 days (range 6-330 days) for AQP4-NMOSD (p = 0.01). All patients with MOGAD recovered, but 2 of 11 (18%) patients with AQP4-NMOSD died of the attack. For AQP4-NMOSD, Black race was overrepresented for attacks requiring ventilatory support vs those without these episodes (5 of 11 [45%] vs 88 of 457 [19%]; p = 0.045). DISCUSSION: Ventilatory support is rarely required for MOGAD and AQP4-NMOSD attacks, and the indications differ. Compared to MOGAD, these attacks in AQP4-NMOSD may have higher morbidity and mortality, and those of Black race were more predisposed, which we suspect may relate to socially mediated health inequality.

FIO2 Trajectory as a Pragmatic Intermediate Marker in Acute Hypoxic Respiratory Failure.

BACKGROUND: Several markers of oxygenation are used as prognostic markers in acute hypoxemic respiratory failure. Real-world use is limited by the need for invasive measurements and unreliable availability in the electronic health record. A pragmatic, reliable, and accurate marker of acute hypoxemic respiratory failure is needed to facilitate epidemiologic studies, clinical trials, and shared decision-making with patients. [Formula: see text] is easily obtained at the bedside and from the electronic health record. The [Formula: see text] trajectory may be a valuable marker of recovery in patients with acute hypoxemic respiratory failure. METHODS: This was a historical cohort study of adult subjects admitted to an ICU with acute hypoxemic respiratory failure secondary to community-acquired pneumonia and/or ARDS. RESULTS: Our study included 2,670 subjects. [Formula: see text] and [Formula: see text] were consistently more available than was [Formula: see text] in the electronic health record: ([Formula: see text] vs [Formula: see text] vs [Formula: see text] : 100 vs 100 vs 72.8% on day 1, and 100 vs 99 vs 21% on day 5). A worsening [Formula: see text] trajectory was associated with reduced ventilator-free days. From days 2 to 5, every increase in [Formula: see text] by 10% from the previous day was associated with fewer ventilator-free days (on day 2: adjusted mean -1.25 [95% CI -1.45 to -1.05] d, P < .001). The [Formula: see text] trajectory also provided prognostic information. On days 3 - 5, an increase in [Formula: see text] from the previous day was associated with increased ventilator-free days (on day 3: adjusted mean 2.09 (95% CI 1.44-2.74) d; P < .001). [Formula: see text] models did not add predictive information compared with models with [Formula: see text] alone (on day 2: adjusted [Formula: see text] vs [Formula: see text] R2 0.122 vs 0.119; and on day 3: 0.153 vs 0.163). CONCLUSIONS: [Formula: see text] and [Formula: see text] are pragmatic and readily available intermediate prognostic markers in acute hypoxic respiratory failure. The [Formula: see text] trajectory in the first 5 d of ICU admission provided important prognostic information (ventilator-free days). Although the [Formula: see text] trajectory was also associated with ventilator-free days, it did not provide more information than the [Formula: see text] trajectory alone.

Epidemiology, Risk Factors, and Outcomes of Diffuse Alveolar Hemorrhage After Hematopoietic Stem Cell Transplantation.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is an uncommon complication of hematopoietic stem cell transplantation (HCT) that carries high morbidity and mortality. Limited contemporary data are available regarding the incidence, outcomes, and risk factors for DAH. RESEARCH QUESTION: What are the incidence, outcomes, and risk factors for DAH developing after HCT? METHODS: This was a single-center retrospective cohort study of patients who underwent HCT between January 1, 2005, and December 31, 2016. The incidence and outcomes of DAH development were evaluated. A multivariate logistic regression model was used to analyze differences between survivors and nonsurvivors. RESULTS: Of 4,350 patients undergoing first-time HCT, DAH was diagnosed in 99 (2.3%). DAH was seen in 40 of 3,536 autologous HCT recipients (1.1%) and 59 of 814 allogeneic HCT recipients (7.2%). Mean age was 53 ± 13 years, and median time of DAH diagnosis was 126 days (interquartile range, 19-349 days) after HCT. In-hospital mortality and mortality 1 year after DAH diagnosis were 55.6% and 76.8%, respectively. DAH diagnosis more than 30 days after transplantation (OR, 7.06; 95% CI, 1.65-30.14), low platelet count (OR, 0.98; 95% CI, 0.96-1.0; P = .02), elevated international normalized ratio (INR; OR, 4.08; 95% CI, 0.64-25.88; P = .046) and need for invasive mechanical ventilation (OR, 8.18; 95% CI, 1.9-35.21) were associated with higher in-hospital mortality. Steroid treatment did not alter mortality (P = .80) or length of stay (P = .65). However, among those who received steroids, survival was higher in whose who received modest-dose steroids (< 250 mg methylprednisolone equivalent/d) compared with those who received high-dose steroids (≥ 250 mg methylprednisolone equivalent/d; OR, 0.21; 95% CI, 0.07-0.72). INTERPRETATION: The mortality of DAH after HCT remains high, and DAH can occur long after transplantation. Later development of DAH (>30 days after HCT), need for invasive mechanical ventilation, thrombocytopenia, and elevated INR are all associated with worse outcomes.

Pretransplant Risk Factors Can Predict Development of Acute Respiratory Distress Syndrome after Hematopoietic Stem Cell Transplantation.

Rationale: Acute respiratory distress syndrome (ARDS) is a common complication after hematopoietic stem cell transplantation (HCT) and is a major contributor to nonrelapse mortality. Objectives: To better understand pretransplant risk factors for developing ARDS after HCT. Methods: This is a single-center observational study comparing risk factors for ARDS development in 164 patients who went on to develop post-HCT ARDS compared with 492 patients who did not. The patients were matched 1 to 3 on age, sex, type of transplant (allogeneic vs. autologous), and underlying disease. Pertinent risk factors were analyzed separately in multivariable conditional logistic regression after adjustment for a priori variables known to be associated with ARDS development. Results: Patients with ARDS were more likely to have a lower pretransplant pulmonary function as measured by forced vital capacity (FVC) (odds ratio [OR], 0.54 [0.42-0.70] per liter increase in FVC; P < 0.001), forced expiratory volume in one second (FEV1) (OR, 0.52 [0.38-0.71] per liter increase in FEV1; P < 0.001) and diffusing capacity (OR, 0.92 [0.88-0.96] per ml/min/mm Hg increase in diffusing capacity; P < 0.001). Several laboratory indices were predictive of subsequent ARDS development including elevated AST (aspartate aminotransferase) (OR, 1.01 [1.00-1.01]; P < 0.008), lower serum albumin (OR, 0.44 [0.30-0.66]; P < 0.001), lower pretransplant hemoglobin (OR, 0.82 [0.73-0.92]; P = 0.001), and lower leukocyte count (OR, 0.88 [0.79-0.99]; P < 0.03). Patients who went on to develop ARDS were more likely to have been hospitalized in the year before the transplant (OR, 1.11 [1.04-1.20]; P = 0.003), and required invasive or noninvasive ventilation during that hospitalization. Lastly, patients with ARDS were significantly more likely to have received carboplatin, thalidomide, methotrexate, and cisplatin than the non-ARDS control subjects. Conclusions: Several risk factors for developing ARDS after HCT are identifiable at the time of transplantation, well before the development of critical illness and ARDS. The identification of risk factors long before ARDS develops is relatively unique to the HCT population. Further work is needed to develop usable risk prediction tools in this setting.

Characteristics and Outcome of Periengraftment Respiratory Distress Syndrome after Autologous Hematopoietic Cell Transplant.

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives: To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods: This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results: Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5-6.2; P = 0.002). Conclusions: PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.