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OBJECTIVE: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. METHODS: We use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP-Seq. We next developed a radio-labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. RESULTS: PhIP-Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free-survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. CONCLUSION: We used PhIP-Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5-IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity.
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BACKGROUND AND OBJECTIVE: Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in-hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE-FILD) including IPF and non-IPF ILDs. METHODS: AE-FILD cases over a 10-year period were filtered using a code-based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone-equivalent for ≥3 days within the first 72 h of admission) and in-hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. RESULTS: Across two centres a total of 107 AE-FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre-admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00-16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all-cause mortality in non-IPF patients (HR 0.21; 95% CI 0.04-0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all-cause mortality (HR 3.25; 95% CI 1.56-6.77; p < 0.01). CONCLUSION: In this two-centre retrospective study of 107 patients, AE-FILD demonstrates a high risk of mortality, at a level similar to that seen for AE-IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE-FILD.
Subject(s)
Disease Progression , Hospital Mortality , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Humans , Male , Female , Retrospective Studies , Aged , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/physiopathology , Middle Aged , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/mortality , Glucocorticoids/therapeutic use , Treatment Outcome , Prednisolone/therapeutic use , Lung TransplantationABSTRACT
BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied across different types of antigen exposure. RESEARCH QUESTION: In patients with fHP, do disease outcomes and response to treatment vary by antigen type? STUDY DESIGN AND METHODS: A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival. RESULTS: A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P = .20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P = .88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P = .047). INTERPRETATION: Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen.
Subject(s)
Alveolitis, Extrinsic Allergic , Immunosuppressive Agents , Mycophenolic Acid , Humans , Alveolitis, Extrinsic Allergic/physiopathology , Alveolitis, Extrinsic Allergic/diagnosis , Alveolitis, Extrinsic Allergic/immunology , Male , Female , Aged , Immunosuppressive Agents/therapeutic use , Middle Aged , Mycophenolic Acid/therapeutic use , Azathioprine/therapeutic use , Treatment Outcome , Canada/epidemiology , Antigens/immunology , Retrospective Studies , RegistriesABSTRACT
Rationale: Social isolation and loneliness are gaining recognition for their role in health outcomes, yet they have not been defined in people with chronic obstructive pulmonary disease (COPD). Objective: To determine the national prevalence of and characteristics associated with social isolation and loneliness in people with COPD. Methods: This is a cross-sectional study of community-dwelling adults aged ⩾50 years in the nationally representative HRS (Health and Retirement Study) (2016-2018). Participants self-reported COPD and supplemental oxygen use and were categorized into three groups: 1) no COPD; 2) COPD; and 3) COPD on oxygen. Social isolation was defined using a nine-item scale indicating minimal household contacts, social network interaction, and community engagement. Loneliness was measured using the 3-Item UCLA Loneliness Scale. Multivariable logistic regression defined prevalence and associated characteristics for both. Results: Participants (n = 10,384) were on average 68 years old (standard deviation, ±10.5), 54% female, 10% Black, 11% self-reported COPD, and 2% self-reported supplemental oxygen. Overall, 12% were socially isolated, 12% lonely, and 3% both socially isolated and lonely. People with COPD had a higher adjusted prevalence of social isolation (no COPD: 11%; COPD: 16%; COPD on oxygen: 20%; P < 0.05) and loneliness (no COPD: 11%; COPD: 18%; COPD on oxygen: 22%; P < 0.001). In those with COPD, characteristics associated with social isolation (P < 0.05) included sex (men: 22%; women: 13%), non-Hispanic White ethnicity (White: 19%; Black: 7%), low net worth (<$6,000: 32%; $81,001-$239,000: 10%), depression (depression: 24%; no depression: 14%), having difficulty with one or more activities of daily living (one or more difficulty: 22%; no difficulty: 14%), and current cigarette use (current: 24%; never: 13%). Characteristics associated with loneliness (P < 0.05) included younger age (50-64 yr: 22%; 75-84 yr: 12%), being single (single: 32%; married: 12%), depression (depression: 36%; no depression: 13%), having difficulty with one or more activities of daily living (one or more difficulty: 29%; no difficulty: 15%), diabetes (diabetes: 26%; no diabetes: 17%), and heart disease (heart disease 23%; no heart disease: 17%). Conclusions: Nearly one in six adults with COPD experience social isolation, and one in five experience loneliness, with almost twice the prevalence among those on supplemental oxygen compared with the general population. Demographic and clinical characteristics identify those at highest risk to guide clinical and policy interventions.
Subject(s)
Diabetes Mellitus , Heart Diseases , Pulmonary Disease, Chronic Obstructive , Male , Humans , Adult , Female , Aged , Loneliness , Activities of Daily Living , Prevalence , Cross-Sectional Studies , Social Isolation , Pulmonary Disease, Chronic Obstructive/epidemiology , OxygenABSTRACT
PURPOSE OF REVIEW: We highlight recent advances in the development and use of digital outcome measures in clinical trials, focusing on how to select the appropriate technology, use digital data to define trial endpoints, and glean important lessons from current experiences with digital outcome measures in pulmonary medicine. RECENT FINDINGS: A review of emerging literature demonstrates that the use of digital health technologies, particularly pulse oximeters, remote spirometers, accelerometers, and Electronic Patient-Reported Outcomes, has surged in both pulmonary practice and clinical trials. Lessons learned from their use can help researchers to design the next generation of clinical trials leveraging digital outcomes to improve health. SUMMARY: In pulmonary diseases, digital health technologies provide validated, reliable, and usable data on patients in real-world environments. More broadly, digital endpoints have accelerated innovation in clinical trial design, improved clinical trial efficiency, and centered patients. As investigators adopt digital health technologies, it is important to follow a framework informed by both the opportunities and challenges of digitization. Successful use of digital health technologies will transform clinical trials by improving accessibility, efficiency, patient-centricity, and expanding opportunities for personalized medicine.
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Telemedicine , Humans , Outcome Assessment, Health CareABSTRACT
Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases (CTD). Establishing autoimmunity in ILD impacts prognosis and treatment. ILD patients are screened for autoimmunity by assaying for anti-nuclear autoantibodies, rheumatoid factors and other non-specific tests. However, this approach has not been rigorously validated and may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. Here, we use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct a large, multi-center unbiased autoantibody discovery screen of ILD patients and controls. PhIP-Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among these 17 candidates, we validated Cadherin Related Family Member 5 (CDHR5) as an autoantigen and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, subjects not previously diagnosed with autoimmunity. Lung tissue of CDHR5 autoreactive patients showed transcriptional profiles consistent with activation of NFκB signaling and upregulation of chitotriosidase (CHIT1), a molecular pathway linked to fibrosis. Our study shows PhIP-Seq uncovers novel autoantibodies in ILD patients not revealed by standard clinical tests. Furthermore, CDHR5 autoantibodies may define a novel molecular endotype of ILD characterized by inflammation and fibrosis.
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BACKGROUND: Epidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system. STUDY DESIGN AND METHODS: We applied a previously validated algorithm to the EHR of a community-based healthcare system to identify ILD cases between 2012-2020. We then extracted disease-specific characteristics and outcomes using fully automated data-extraction algorithms and natural language processing of selected free-text. RESULTS: We identified a community cohort of 5,399 ILD patients (prevalence = 118 per 100,000). Pulmonary function tests (71%) and serologies (54%) were commonly used in the diagnostic evaluation, whereas lung biopsy was rare (5%). IPF was the most common ILD diagnosis (n = 972, 18%). Prednisone was the most commonly prescribed medication (911, 17%). Nintedanib and pirfenidone were rarely prescribed (n = 305, 5%). ILD patients were high-utilizers of inpatient (40%/year hospitalized) and outpatient care (80%/year with pulmonary visit), with sustained utilization throughout the post-diagnosis study period. DISCUSSION: We demonstrated the feasibility of robustly characterizing a variety of patient-level utilization and health services outcomes in a community-based EHR cohort. This represents a substantial methodological improvement by alleviating traditional constraints on the accuracy and clinical resolution of such ILD cohorts; we believe this approach will make community-based ILD research more efficient, effective, and scalable.
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Electronic Health Records , Lung Diseases, Interstitial , Humans , Lung Diseases, Interstitial/diagnosis , Lung , AlgorithmsABSTRACT
There is increasing attention being given to opportunities and approaches to advance health equity using implementation science. To reduce disparities in health, it is crucial that an equity lens is integrated from the earliest stages of the implementation process. In this paper, we outline four key pre-implementation steps and associated questions for implementation researchers to consider that may help guide selection and design of interventions and associated implementation strategies that are most likely to reach and be effective in reducing health disparities among vulnerable persons and communities.
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Health Equity , Implementation Science , Healthcare Disparities , Humans , Research PersonnelABSTRACT
BACKGROUND: Mortality risk assessment in interstitial lung disease (ILD) is challenging. Our objective was to determine the prognostic significance of BMI and change in weight in the most common fibrotic ILD subtypes. RESEARCH QUESTION: Could BMI and weight loss over time be reliable prognostic indicators in patients with fibrotic ILD? STUDY DESIGN AND METHODS: This observational retrospective multicenter cohort study enrolled patients with fibrotic ILD from the six-center CAnadian REgistry for Pulmonary Fibrosis (CARE-PF, derivation) and the ILD registry at the University of California, San Francisco (UCSF, validation). Patients were subcategorized as underweight (BMI < 18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), or obese (BMI > 30). Annual change in weight was calculated for all years of follow-up as the slope of best fit using the least square method based on every available measurement. Separate multivariable analyses evaluated the associations of BMI and change in weight with mortality, adjusting for common prognostic variables. RESULTS: The derivation and validation cohorts included 1,786 and 1,779 patients, respectively. Compared with patients with normal BMI, mortality was highest in patients who were underweight (hazard ratio [HR], 3.19; 95% CI, 1.88-5.43; P < .001) and was lowest in those who were overweight (HR, 0.52; 95% CI, 0.36-0.75; P < .001) or obese (HR, 0.55; 95%CI, 0.37-0.83; P < .001) in the analysis adjusted for the ILD-GAP (gender, age, physiology) Index. Patients who had a weight loss of at least 2 kg within 1 year had increased risk of death in the subsequent year (HR, 1.41; 95% CI, 1.01-1.97; P = .04) after adjustment for the ILD-GAP Index and baseline BMI category, with a plateau in risk for patients with greater weight loss. Consistent results were observed in the validation cohort. INTERPRETATION: Both BMI and weight loss are independently associated with 1-year mortality in fibrotic ILD. BMI and weight loss may be clinically useful prognostic indicators in fibrotic ILD.
Subject(s)
Lung Diseases, Interstitial , Thinness , Body Mass Index , Canada/epidemiology , Cohort Studies , Humans , Lung Diseases, Interstitial/complications , Obesity/complications , Obesity/epidemiology , Overweight/complications , Retrospective Studies , Thinness/complications , Weight LossABSTRACT
We are in the midst of transformative innovation in health care delivery and clinical trials in idiopathic pulmonary fibrosis (IPF). Health systems are uniquely positioned at the crossroad of these shifting paradigms, equipped with the resources to expand the research pipeline in IPF through visionary leadership and targeted investments. The authors hope that by prioritizing development of health information technology, supporting a broader range of clinical trial designs, and cultivating broad stakeholder engagement, health systems will generate data to address knowledge-evidence-practice gaps in IPF. This will continue to improve the ability to deliver high-quality, safe, and effective care.
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Clinical Trials as Topic , Idiopathic Pulmonary Fibrosis/drug therapy , Delivery of Health Care , Humans , Medical InformaticsABSTRACT
Women are under-represented at the highest levels of leadership in health care, so many institutions have started forming "women in medicine" affinity groups. In this The Clinical Teacher's Toolbox, we review the history of women's professional peer-to-peer networking groups in health care, describe the rationale for establishing a women's group, discuss the goals and common content covered by successful women's groups, share best practices on forming and sustaining women's groups, and describe common pitfalls to avoid. When forming a women's group, identifying the group's vision, mission, and primary aim statements are important, and early meetings should deliberately establish a tone of inclusion. We acknowledge that the term "women's groups" implies that gender identity is binary - in reality, these groups are for all who want to combat gender inequities in health care. While early stages of women's groups typically focus on community-building, peer networking, and inviting guest speakers to speak about relevant topics, successful groups often ultimately pivot to advocacy, internal capacity-building, evaluation, and dissemination. To sustain and maintain the group, succession planning, regular opportunities for evaluation, and deliberate planning are essential. Although usual principles of successful small group creation apply, this article outlines unique considerations for how women's groups can advance gender equity.
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Gender Identity , Women , Female , Humans , Leadership , MaleABSTRACT
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare, chronic lung disease associated with substantial symptom burden, morbidity, and cost. Delivery of high-quality effective care in IPF requires understanding health-care resource utilization (HRU) patterns; however, longitudinal data from real-world populations are limited. RESEARCH QUESTION: This study aimed to define HRU attributable to IPF by evaluating a longitudinal cohort of community patients with IPF compared with matched control subjects. STUDY DESIGN AND METHODS: Incident IPF cases were identified in the Kaiser Permanente Northern California electronic health records (2000-2015) using case-validated code-based algorithms. IPF cases were compared with matched control subjects by age, sex, and length of enrollment. Annual rates of HRU measures were assessed during the 5 years pre- and postdiagnosis. Poisson generalized estimating equations were used to estimate adjusted case-control differences in HRU. IPF treatment trends were assessed before and after the availability of IPF-specific medications. RESULTS: A total of 691 IPF cases were identified and matched with 3,452 control subjects. Adjusted rates of all diagnostic procedures were significantly increased (P < .001) for IPF cases compared with control subjects in both the pre- and postindex periods, including chest CT scans (pre-relative risk [RR], 80.35; post-RR, 32.79), 6-min walk tests (pre-RR, 20.81; post-RR, 34.49), and pulmonary function tests (pre-RR, 9.50; post-RR, 13.24). All-cause hospitalizations (pre-RR, 1.42; post-RR, 2.33) and outpatient visits (pre-RR, 1.22; post-RR, 1.80) were significantly higher among cases compared with control subjects during both the preindex (P < .05) and postindex (P < .001) periods. We observed use of immunosuppressive and IPF-specific therapies prior to diagnosis, and high rates of corticosteroid use before and after diagnosis. INTERPRETATION: This study defines a marked increase in HRU in patients with IPF compared with control subjects, with accelerated use beginning at least 1 year prediagnosis and elevated use sustained over the following 5 years. To our knowledge, this is the first study to evaluate longitudinal medication trends in IPF. Collectively, this information is foundational to advancing IPF care delivery models and supporting clinical decision-making.
Subject(s)
Idiopathic Pulmonary Fibrosis/therapy , Patient Acceptance of Health Care/statistics & numerical data , Aged , Aged, 80 and over , California , Case-Control Studies , Cohort Studies , Facilities and Services Utilization , Female , Health Services/statistics & numerical data , Hospitalization/statistics & numerical data , Humans , Idiopathic Pulmonary Fibrosis/complications , Male , Middle Aged , Procedures and Techniques UtilizationABSTRACT
BACKGROUND AND OBJECTIVE: AE-IPF has profound prognostic implications, preceding approximately half of all IPF-related deaths. Despite this clinical significance, there are limited data to guide management decisions. Corticosteroids remain the mainstay of treatment despite a lack of strong supporting evidence and mounting concern that they may be harmful. We assessed the impact of corticosteroid therapy on in-hospital mortality in AE-IPF patients. METHODS: AE-IPF subjects were retrospectively identified in the UCSF medical centre's electronic health records from 1 January 2010 to 1 August 2018 using a code-based algorithm followed by case validation. The relationship between corticosteroid treatment and in-hospital mortality was assessed using a Cox model and a propensity score to control for confounding by indication. Secondary outcomes included hospital readmissions and overall survival. RESULTS: In total, 82 AE-IPF subjects were identified, of whom 37 patients (45%) received corticosteroids. AE-IPF subjects treated with corticosteroids were more likely to require ICU level care and mechanical ventilation. There was no statistically significant association between corticosteroid treatment and in-hospital mortality (propensity score weighted, adjusted HR: 1.31; 95% CI: 0.26-6.55; P = 0.74). Overall survival was reduced in AE-IPF subjects receiving corticosteroids (HR: 6.17; 95% CI: 1.35-28.14; P = 0.019). CONCLUSION: Our study found no evidence that corticosteroid use improves outcomes in IPF patients admitted to the hospital with acute exacerbation. Furthermore, corticosteroid use may contribute to reduced overall survival following an exacerbation. Observational cohort studies using larger real-world cohorts can more definitively assess the relationship between corticosteroid treatment and short-term outcomes in AE-IPF.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Treatment Failure , Aged , Disease Progression , Female , Hospital Mortality , Humans , Idiopathic Pulmonary Fibrosis/mortality , Male , Middle Aged , Prognosis , Proportional Hazards Models , Respiration, Artificial , Retrospective Studies , Treatment OutcomeABSTRACT
Interstitial lung disease (ILD) is a diverse group of disorders typically with insidious onset. Diagnosis and management largely occur in the outpatient setting; however, ILD can present acutely necessitating hospitalization. Effective inpatient management requires the clinician to establish an accurate diagnosis and understand the natural history and treatment responsiveness of each ILD subtype. We propose a general framework for approaching the evaluation of hospitalized patients with ILD, and provide focused guidance on key inpatient diagnostic and management decisions.
Subject(s)
Hospitalists , Hospitalization , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/therapy , Adrenal Cortex Hormones/therapeutic use , Bronchoscopy/methods , Hospitalists/standards , Hospitalization/trends , HumansABSTRACT
INTRODUCTION: Critical illness is a well-recognized cause of neuromuscular weakness and impaired physical functioning. Physical therapy (PT) has been demonstrated to be safe and effective for critically ill patients. The impact of such an intervention on patients receiving extracorporeal membrane oxygenation (ECMO) has not been well characterized. We describe the feasibility and impact of active PT on ECMO patients. METHODS: We performed a retrospective cohort study of 100 consecutive patients receiving ECMO in the medical intensive care unit of a university hospital. RESULTS: Of the 100 patients receiving ECMO, 35 (35%) participated in active PT; 19 as bridge to transplant and 16 as bridge to recovery. Duration of ECMO was 14.3 ± 10.9 days. Patients received 7.2 ± 6.5 PT sessions while on ECMO. During PT sessions, 18 patients (51%) ambulated (median distance 175 feet, range 4 to 2,800) and 9 patients were on vasopressors. Whilst receiving ECMO, 23 patients were liberated from invasive mechanical ventilation. Of the 16 bridge to recovery patients, 14 (88%) survived to discharge; 10 bridge to transplant patients (53%) survived to transplantation, with 9 (90%) surviving to discharge. Of the 23 survivors, 13 (57%) went directly home, 8 (35%) went to acute rehabilitation, and 2 (9%) went to subacute rehabilitation. There were no PT-related complications. CONCLUSIONS: Active PT, including ambulation, can be achieved safely and reliably in ECMO patients when an experienced, multidisciplinary team is utilized. More research is needed to define the barriers to PT and the impact on survival and long-term functional, neurocognitive outcomes in this population.
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Early Ambulation/methods , Extracorporeal Membrane Oxygenation/rehabilitation , Physical Therapy Modalities , Critical Illness , Humans , Intensive Care Units , Retrospective StudiesABSTRACT
BACKGROUND: Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. AIMS: We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. METHODS: Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. RESULTS: One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. CONCLUSIONS: uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.