Scoring donor lungs for graft failure risk: The Lung Donor Risk Index (LDRI).

Lung transplantation lags behind other solid organ transplants in donor lung utilization due, in part, to uncertainty regarding donor quality. We sought to develop an easy-to-use donor risk metric that, unlike existing metrics, accounts for a rich set of donor factors. Our study population consisted of n = 26 549 adult lung transplant recipients abstracted from the United Network for Organ Sharing Standard Transplant Analysis and Research file. We used Cox regression to model graft failure (GF; earliest of death or retransplant) risk based on donor and transplant factors, adjusting for recipient factors. We then derived and validated a Lung Donor Risk Index (LDRI) and developed a pertinent online application (https://shiny.pmacs.upenn.edu/LDRI_Calculator/). We found 12 donor/transplant factors that were independently predictive of GF: age, race, insulin-dependent diabetes, the difference between donor and recipient height, smoking, cocaine use, cytomegalovirus seropositivity, creatinine, human leukocyte antigen (HLA) mismatch, ischemia time, and donation after circulatory death. Validation showed the LDRI to have GF risk discrimination that was reasonable (C = 0.61) and higher than any of its predecessors. The LDRI is intended for use by transplant centers, organ procurement organizations, and regulatory agencies and to benefit patients in decision-making. Unlike its predecessors, the proposed LDRI could gain wide acceptance because of its granularity and similarity to the Kidney Donor Risk Index.

The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation.

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

Intimate Partner Violence: Childhood Witnessing and Subsequent Experiences of College Undergraduates.

Previous work links witnessing adult violence in the home during childhood ("witnessing") and adolescent relationship violence, but studies are limited to recent experiences with one or two outcomes, missing the holistic viewpoint describing lifetime experiences across multiple types of violence. We measured associations between witnessing and victimization (being harmed by violence) and perpetration (causing harm by violence) among males and females for the three most common types of adolescent relationship violence (physical, sexual, and emotional), and we assessed whether students experienced multiple outcomes ("polyvictimization/ polyperpetration"). We also compared sex-specific differences to assess for additive effect modification. We used an anonymous, cross-sectional survey with 907 undergraduates attending randomly selected classes at three urban East Coast colleges. Multiple logistic regression and marginal standardization were used to estimate predicted probabilities for each outcome among witnesses and non-witnesses; additive interaction by sex was assessed using quantifiable measures. 214 (24%) students reported witnessing and 403 (44%) students experienced adolescent relationship violence, with 162 (17.9%) and 37 (4.1%) experiencing polyvictimization and polyperpetration, respectively. Witnesses had higher risk than non-witnesses for physical, sexual, and emotional victimization and perpetration. Notably, witnesses also had higher risk for polyvictimization and polyperpetration. Additive effect modification by sex was insignificant at 95% confidence bounds, but distinct patterns emerged for males and females. Except for sexual victimization, female witnesses were more likely than female non-witnesses to experience all forms of victimization, including polyvictimization; they also had higher risk for perpetration, particularly physical perpetration. In contrast, victimization outcomes did not differ for male witnesses, but male witnesses were more likely than male non-witnesses to perpetrate all forms of violence, including polyperpetration.

Abnormal glucose tolerance and the 50-gram glucose challenge test in Cystic fibrosis.

Diabetes has emerged as a major co-morbidity in cystic fibrosis (CF). The 75 g oral glucose tolerance test (OGTT) is used to screen for CF-related diabetes (CFRD) but is inconvenient, and adherence to screening is poor. The 50 g glucose challenge test (GCT) is shorter, performed non-fasting, and may serve to pre-screen the subset of individuals requiring confirmatory OGTT. We performed a pilot study in twenty-seven CF individuals across the glucose tolerance spectrum to test whether the GCT could identify subjects with abnormal glucose tolerance defined as 2-h OGTT glucose ≥7.8 mmol/L (2 h-AGT) or 1-h defined as 1-hr OGTT glucose ≥11.1 mmol/L (1 h-AGT). A GCT threshold of 8.1 mmol/L was 73% sensitive and 63% specific for 2hr-AGT and 80% sensitive and 65% specific for 1hr-AGT. Therefore, a screening GCT may reduce need for confirmatory OGTT for identifying AGT but a larger study is warranted to identify a robust cutoff for CFRD.

Infections after pediatric ambulatory surgery: Incidence and risk factors.

OBJECTIVE: To describe the epidemiology of surgical site infections (SSIs) after pediatric ambulatory surgery. DESIGN: Observational cohort study with 60 days follow-up after surgery. SETTING: The study took place in 3 ambulatory surgical facilities (ASFs) and 1 hospital-based facility in a single pediatric healthcare network.ParticipantsChildren <18 years undergoing ambulatory surgery were included in the study. Of 19,777 eligible surgical encounters, 8,502 patients were enrolled. METHODS: Data were collected through parental interviews and from chart reviews. We assessed 2 outcomes: (1) National Healthcare Safety Network (NHSN)-defined SSI and (2) evidence of possible infection using a definition developed for this study. RESULTS: We identified 21 NSHN SSIs for a rate of 2.5 SSIs per 1,000 surgical encounters: 2.9 per 1,000 at the hospital-based facility and 1.6 per 1,000 at the ASFs. After restricting the search to procedures completed at both facilities and adjustment for patient demographics, there was no difference in the risk of NHSN SSI between the 2 types of facilities (odds ratio, 0.7; 95% confidence interval, 0.2-2.3). Within 60 days after surgery, 404 surgical patients had some or strong evidence of possible infection obtained from parental interview and/or chart review (rate, 48 SSIs per 1,000 surgical encounters). Of 306 cases identified through parental interviews, 176 cases (57%) did not have chart documentation. In our multivariable analysis, older age and black race were associated with a reduced risk of possible infection. CONCLUSIONS: The rate of NHSN-defined SSI after pediatric ambulatory surgery was low, although a substantial additional burden of infectious morbidity related to surgery might not have been captured by standard surveillance strategies and definitions.

User Testing an Information Foraging Tool for Ambulatory Surgical Site Infection Surveillance.

BACKGROUND: Surveillance for surgical site infections (SSIs) after ambulatory surgery in children requires a detailed manual chart review to assess criteria defined by the National Health and Safety Network (NHSN). Electronic health records (EHRs) impose an inefficient search process where infection preventionists must manually review every postsurgical encounter (< 30 days). Using text mining and business intelligence software, we developed an information foraging application, the SSI Workbench, to visually present which postsurgical encounters included SSI-related terms and synonyms, antibiotic, and culture orders. OBJECTIVE: This article compares the Workbench and EHR on four dimensions: (1) effectiveness, (2) efficiency, (3) workload, and (4) usability. METHODS: Comparative usability test of Workbench and EHR. Objective test metrics are time per case, encounters reviewed per case, time per encounter, and retrieval of information meeting NHSN definitions. Subjective measures are cognitive load using the National Aeronautics and Space Administration (NASA) Task Load Index (NASA TLX), and a questionnaire on system usability and utility. RESULTS: Eight infection preventionists participated in the test. There was no difference in effectiveness as subjects retrieved information from all cases, using both systems, to meet the NHSN criteria. There was no difference in efficiency in time per case between the Workbench and EHR (8.58 vs. 7.39 minutes, p = 0.36). However, with the Workbench subjects opened fewer encounters per case (3.0 vs. 7.5, p = 0.002), spent more time per encounter (2.23 vs. 0.92 minutes, p = 0.002), rated the Workbench lower in cognitive load (NASA TLX, 24 vs. 33, p = 0.02), and significantly higher in measures of usability. CONCLUSION: Compared with the EHR, the Workbench was more usable, short, and reduced cognitive load. In overall efficiency, the Workbench did not save time, but demonstrated a shift from between-encounter foraging to within-encounter foraging and was rated as significantly more efficient. Our results suggest that infection surveillance can be better supported by systems applying information foraging theory.

Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 µg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each µg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease.

Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.

RATIONALE: Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation. OBJECTIVE: We evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model. METHODS: We conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaO2/FiO2 ≤200 with allograft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort. RESULTS: In the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion fraction of inspired oxygen were associated with primary graft dysfunction. Donor obesity was associated with a lower risk for primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1% [95% confidence interval, 85.3-92.8] and 83.3% [95% confidence interval, 78.5-88.2], respectively), but low positive predictive value. CONCLUSIONS: Several recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value, to rule out high risk for primary graft dysfunction.

Massive donor transfusion potentially increases recipient mortality after lung transplantation.

OBJECTIVE: Donor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant. METHODS: Donor and recipient data were abstracted from the Organ Procurement and Transplantation Network database updated through June 30, 2014, which included 86,398 potential donors and 16,255 transplants. Using the United Network for Organ Sharing 4-level designation of transfusion (no blood, 1-5 units, 6-10 units, and >10 units, massive), we analyzed all-cause mortality at 30-days with the use of logistic regression adjusted for confounders (ischemic time, donor age, recipient diagnosis, lung allocation score and recipient age, and recipient body mass index). Secondary analyses assessed 90-day and 1-year mortality and hospital length of stay. RESULTS: Of the 16,255 recipients transplanted, 8835 (54.35%) donors received at least one transfusion. Among those transfused, 1016 (6.25%) received a massive transfusion, defined as >10 units. Those donors with massive transfusion were most commonly young trauma patients. After adjustment for confounding variables, donor massive transfusion was associated significantly with an increased risk in 30-day (P = .03) and 90-day recipient mortality (P = .01) but not 1-year mortality (P = .09). There was no significant difference in recipient length of stay or hospital-free days with respect to donor transfusion. CONCLUSIONS: Massive donor blood transfusion (>10 units) was associated with early recipient mortality after lung transplantation. Conversely, submassive donor transfusion was not associated with increased recipient mortality. The mechanism of increased early mortality in recipients of lungs from massively transfused donors is unclear and needs further study but is consistent with excess mortality seen with primary graft dysfunction in the first 90 days posttransplant.

Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients.

Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.

Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths.

IMPORTANCE: Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children, either singly or in a medication combination. Although metabolic adverse effects have been linked to SGA use in youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has been challenging. OBJECTIVE: To determine whether SGA initiation was associated with an increased risk for incident type 2 diabetes mellitus. Secondary analyses examined the risk associated with multiple-drug regimens, including stimulants and antidepressants, as well as individual SGAs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective national cohort study of Medicaid-enrolled youths between January 2003 and December 2007. In this observational study using national Medicaid Analytic eXtract data files, initiators and noninitiators of SGAs were identified in each month. Included in this study were US youths aged 10 to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for-service arrangement during the study. Those with chronic steroid exposure, a diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were ineligible. The mean follow-up time for all participants was 17.2 months. Youths were followed up until diagnosis of diabetes mellitus or end of follow-up owing to censoring caused by the transition into a Medicaid managed care arrangement or Medicaid ineligibility (the end of available data). Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fitted using weighted logistic regression to estimate the risk for incident diabetes mellitus between initiators and noninitiators. EXPOSURE: A filled SGA prescription. MAIN OUTCOMES AND MEASURES: Incident type 2 diabetes mellitus identified through visit and pharmacy claims during the observation period. RESULTS: Among 107,551 SGA initiators and 1,221,434 noninitiators, the risk for incident diabetes mellitus was increased among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared with youths initiating only SGAs, the risk was higher among SGA initiators who used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95% CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators who were concomitantly using stimulants. As compared with a reference group of risperidone initiators, the risk was higher among those initiating ziprasidone (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21-2.07; P = .001) but not quetiapine fumarate or olanzapine. CONCLUSIONS AND RELEVANCE: The risk for incident type 2 diabetes mellitus was increased among youths initiating SGAs and was highest in those concomitantly using antidepressants. Compared with risperidone, newer antipsychotics were not associated with decreased risk.

Effect of decision support on missed opportunities for human papillomavirus vaccination.

BACKGROUND: Missed opportunities for human papilloma virus (HPV) vaccination are common, presenting a barrier to achieving widespread vaccine coverage and preventing infection. PURPOSE: To compare the impact of clinician- versus family-focused decision support, none, or both on captured opportunities for HPV vaccination. DESIGN: Twelve-month cluster randomized controlled trial conducted in 2010-2011. SETTING/PARTICIPANTS: Adolescent girls aged 11-17 years due for HPV Dose 1, 2, or 3 receiving care at primary care practices. INTERVENTION: Twenty-two primary care practices were cluster randomized to receive a three-part clinician-focused intervention (educational sessions, electronic health record-based alerts, and performance feedback) or none. Within each practice, girls were randomized at the patient level to receive family-focused, automated, educational phone calls or none. Randomization resulted in four groups: clinician-focused, family-focused, combined, or no intervention. MAIN OUTCOME MEASURES: Standardized proportions of captured opportunities (due vaccine received at clinician visit) were calculated among girls in each study arm. Analyses were conducted in 2013. RESULTS: Among 17,016 adolescent girls and their 32,472 visits (14,247 preventive, 18,225 acute), more HPV opportunities were captured at preventive than acute visits (36% vs 4%, p<0.001). At preventive visits, the clinician intervention increased captured opportunities by 9 percentage points for HPV-1 and 6 percentage points for HPV-3 (p≤0.01), but not HPV-2. At acute visits, the clinician and combined interventions significantly improved captured opportunities for all three doses (p≤0.01). The family intervention was similar to none. Results differed by practice setting; at preventive visits, the clinician intervention was more effective for HPV-1 in suburban than urban settings, whereas at acute visits, the clinician intervention was more effective for all doses at urban practices. CONCLUSIONS: Clinician-focused decision support is a more effective strategy than family-focused to prevent missed HPV vaccination opportunities. Given the persistence of missed opportunities even in intervention groups, complementary strategies are needed. This study is registered at clinicaltrials.gov NCT01159093.

Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study.

BACKGROUND: The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone. OBJECTIVE: To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART. DESIGN: Retrospective cohort study. SETTING: Veterans Health Administration. PATIENTS: 4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive. MEASUREMENTS: Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. RESULTS: The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients. LIMITATION: Observational study of predominantly male patients. CONCLUSION: Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effectiveness of decision support for families, clinicians, or both on HPV vaccine receipt.

OBJECTIVE: To improve human papillomavirus (HPV) vaccination rates, we studied the effectiveness of targeting automated decision support to families, clinicians, or both. METHODS: Twenty-two primary care practices were cluster-randomized to receive a 3-part clinician-focused intervention (education, electronic health record-based alerts, and audit and feedback) or none. Overall, 22, 486 girls aged 11 to 17 years due for HPV vaccine dose 1, 2, or 3 were randomly assigned within each practice to receive family-focused decision support with educational telephone calls. Randomization established 4 groups: family-focused, clinician-focused, combined, and no intervention. We measured decision support effectiveness by final vaccination rates and time to vaccine receipt, standardized for covariates and limited to those having received the previous dose for HPV #2 and 3. The 1-year study began in May 2010. RESULTS: Final vaccination rates for HPV #1, 2, and 3 were 16%, 65%, and 63% among controls. The combined intervention increased vaccination rates by 9, 8, and 13 percentage points, respectively. The control group achieved 15% vaccination for HPV #1 and 50% vaccination for HPV #2 and 3 after 318, 178, and 215 days. The combined intervention significantly accelerated vaccination by 151, 68, and 93 days. The clinician-focused intervention was more effective than the family-focused intervention for HPV #1, but less effective for HPV #2 and 3. CONCLUSIONS: A clinician-focused intervention was most effective for initiating the HPV vaccination series, whereas a family-focused intervention promoted completion. Decision support directed at both clinicians and families most effectively promotes HPV vaccine series receipt.

Clinical risk factors for primary graft dysfunction after lung transplantation.

RATIONALE: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. OBJECTIVES: We sought to identify donor, recipient, and perioperative risk factors for PGD. METHODS: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. MEASUREMENTS AND MAIN RESULTS: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0-1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P = 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P < 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P = 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P = 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P < 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P < 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P < 0.001) mortality. CONCLUSIONS: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357).

A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation.

BACKGROUND: We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research. METHODS: Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. RESULTS: PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p < 0.001 each). CONCLUSIONS: Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.

Lower serum endocan levels are associated with the development of acute lung injury after major trauma.

PURPOSE: Endocan is a proteoglycan expressed by endothelial cells in the lung that may inhibit leukocyte recruitment and thus prevent the development of acute lung injury (ALI). We tested the association of serum endocan levels with subsequent development of ALI after major trauma. MATERIALS AND METHODS: This was a single-center nested case-control study within a prospective cohort study of major trauma patients. Using an enzyme-linked immunosorbent assay test, we measured endocan levels from admission serum in 24 controls (no ALI) and 24 cases (ALI within 5 days of trauma). Multivariable logistic regression was used to test the association of admission serum endocan levels with subsequent ALI. RESULTS: Patients who developed ALI had lower levels of endocan on admission (mean, 3.5 ± 1.4 ng/mL vs 4.9 ± 2.6 ng/mL in controls; P = .02). For each 1-unit increase in serum endocan level, the odds ratio for ALI development decreased (0.69; 95% confidence interval, 0.49-0.97; P = .03). Lower endocan levels remained associated with a higher incidence of ALI after adjustment for age and illness severity. CONCLUSIONS: Lower levels of serum endocan on admission are associated with subsequent development of ALI in trauma patients. These observations may be explained by endocan-mediated blockade of leukocyte recruitment in the lung.

Risk factors for lymphedema after breast cancer treatment.

BACKGROUND: As cancer treatments evolve, it is important to reevaluate their effect on lymphedema risk in breast cancer survivors. METHODS: A population-based random sample of 631 women from metropolitan Philadelphia, Pennsylvania, diagnosed with incident breast cancer in 1999 to 2001, was followed for 5 years. Risk factor information was obtained by questionnaire and medical record review. Lymphedema was assessed with a validated questionnaire. Using Cox proportional hazards models, we estimated the relative incidence rates [hazard ratios (HR)] of lymphedema with standard adjusted multivariable analyses ignoring interactions, followed by models including clinically plausible treatment interactions. RESULTS: Compared with no lymph node surgery, adjusted HRs for lymphedema were increased following axillary lymph node dissection [ALND; HR, 2.61; 95% confidence interval (95% CI), 1.77-3.84] but not sentinel lymph node biopsy (SLNB; HR, 1.04; 95% CI, 0.58-1.88). Risk was not increased following irradiation [breast/chest wall only: HR, 1.18 (95% CI, 0.80-1.73); breast/chest wall plus supraclavicular field (+/- full axilla): HR, 0.86 (95% CI, 0.48-1.54)]. Eighty-one percent of chemotherapy was anthracycline based. The HR for anthracycline chemotherapy versus no chemotherapy was 1.46 (95% CI, 1.04-2.04), persisting after stratifying on stage at diagnosis or number of positive nodes. Treatment combinations involving ALND or chemotherapy resulted in approximately 4- to 5-fold increases in HRs for lymphedema [e.g., HR of 4.16 (95% CI, 1.32-12.45) for SLNB/chemotherapy/no radiation] compared with no treatment. CONCLUSION: With standard multivariable analyses, ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not. However, risk varied by combinations of exposures. IMPACT: Treatment patterns should be considered when counseling and monitoring patients for lymphedema.