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To describe the development, implementation and reliability and validity testing of the inpatient rehabilitation facility (IRF) Change in Self-Care and Change in Mobility quality measures.We describe the activities involved in developing and implementing the 2 facility-level quality measures, including public comment opportunities. We examined facility-level reliability using split-half testing and Pearson product-moment correlations, Spearman rank correlations, and intraclass correlation coefficients (ICCAll 1117 IRFs in the United States with at least 20 Medicare stays that ended in 2017.Facility-level quality measure scores (N=1117) were derived from data from 427,517 (self-care) and 427,956 (mobility) Medicare fee-for-service and Medicare Advantage IRF patient stays in 2017.Not applicable.Facility-level Change in Self-Care and Change in Mobility quality measure scores and facility Disease-Specific Certification for Stroke Rehabilitation from The Joint Commission were used in validity analysis.The split-half quality measure scores showed strong, positive correlations for the facility-level self-care (Pearson=0.903, Spearman=0.884, ICC=0.903, P.0001) and mobility (Pearson=0.903, Spearman=0.884, ICC= 0.903, P.0001) quality measure scores, providing evidence of reliability. ICCs remained strong when stratifying by provider volume. IRFs with stroke certification had slightly higher mean and median quality measure scores than IRFs without certification, and IRFs with the higher quality measure scores tended to have a higher percentage of certified IRFs.Our analyses support the reliability and validity of the Change in Self-Care and Change in Mobility quality measure scores in IRFs.

To describe the exclusion criteria and updated risk adjustment model developed for the Change in Mobility quality measure in the inpatient rehabilitation facility (IRF) quality reporting program. Facility-level quality measures focused on patient outcomes usually require risk adjustment to account for varied admission characteristics of patients across facilities.This cohort study analyzed admission demographic and clinical factors associated with mobility change scores using the Inpatient Rehabilitation Facility Patient Assessment Instrument (IRF-PAI) data for Medicare patients discharged from IRFs in calendar year 2017.A total of 1129 IRFs in the United States.A total of 493,209 (N=493, 209) Medicare fee-for-service and Medicare Advantage IRF patient stays discharged in calendar year 2017.Not applicable.Mobility change scores using admission and discharge standardized assessment data from the IRF-PAI.Approximately 53% of patients in the study were female, 67% were aged 65-84 years, and nearly 80% were White. In the final risk adjustment model, 105 covariates were included, explaining 20% of variance in mobility change scores. Key risk adjusters included IRF primary diagnosis group, prior indoor ambulation functioning, age older than 90 years, and 14 of the comorbidities. The model showed good calibration across the range of deciles of predicted IRF mobility change scores; the ratio of the average expected to observed change scores ranged from 0.93-1.03, with all but 1 within ±0.03.The updated risk adjustment model uses IRF patients' demographic and clinical characteristics to predict their mobility change scores. The exclusion criteria and resulting risk model are used to calculate the risk adjusted Change in Mobility quality measure scores, enabling comparisons of Change in Mobility scores across IRFs.

After the terrorist attacks on September 11, 2001 (9/11), many rescue/recovery workers developed respiratory symptoms and pulmonary diseases due to their extensive World Trade Center (WTC) dust cloud exposure. Nearly all Fire Department of the City of New York (FDNY) workers were present within 48 h of 9/11 and for the next several months. Since the FDNY had a well-established occupational health service for its firefighters and Emergency Medical Services workers prior to 9/11, the FDNY was able to immediately start a rigorous monitoring and treatment program for its WTC-exposed workers. As a result, respiratory symptoms and diseases were identified soon after 9/11. This focused review summarizes the WTC-related respiratory diseases that developed in the FDNY cohort after 9/11, including WTC cough syndrome, obstructive airways disease, accelerated lung function decline, airway hyperreactivity, sarcoidosis, and obstructive sleep apnea. Additionally, an extensive array of biomarkers has been identified as associated with WTC-related respiratory disease. Future research efforts will not only focus on further phenotyping/treating WTC-related respiratory disease but also on additional diseases associated with WTC exposure, especially those that take decades to develop, such as cardiovascular disease, cancer, and interstitial lung disease.

Rationale: Metabolic syndrome (MetSyn) increases the risk of World Trade Center (WTC) lung injury (LI). However, the temporal relationship of MetSyn, exposure intensity, and lung dysfunction is not...

Background and AimsGastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). Our group has identified predictive biomarkers of GERD in particulate exposed 1stresponders with OAD. Additionally, GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD.MethodsA systematic review of PubMed and EMBASE was performed on February 22, 2022 utilizing keywords focusing on reflux disease and biomarkers. The study was registered with PROSPERO (2022-CRD42022301543). We included: original human studies in English, published after December 31, 2009 focusing on non-invasive biomarkers of GERD. Reflux related conditions included Nonerosive Reflux Disease (NERD) Laryngopharyngeal Disease (LPR), Erosive Esophagitis (EE) and Barretts Esophagus (BE). Predictive measures were synthesized and bias assessed.ResultsPrimary search identified 241 studies. After removing duplicates and applying inclusion/exclusion criteria n=15 articles were identified. Salivary pepsin was the most studied biomarker (n=5) with a significant sensitivity and specificity for GERD and LPR detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest area under curve the receiver operator curve(ROCAUC) 0.94(95% CI; 0.90-0.7). An oral microbiome model includingLautropia,StreptococcusandBacteroidetesshowed the greatest discrimination between BE and controls vsLautropiaalone; sensitivity of 96.9%, specificity of 88.2% and ROCAUCof 0.94(0.81-1.00).ConclusionPrior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability and accuracy of these biomarkers more studies are warranted.WHAT YOU NEED TO KNOWBACKGROUNDGastroesophageal reflux disease (GERD) is a prevalent GI disorder which may complicate conditions such as obstructive airways disease (OAD). GERD diagnosis and treatment is costly, and invasive. In light of these clinical concerns our aim was to systematically review studies identifying non-invasive, multiOmic and multi-compartmental biomarkers of GERD.FINDINGSSalivary pepsin was the most studied biomarker with a significant sensitivity and specificity for GERD detection. Studies showed that for GERD diagnosis, miR-203 downregulation had the highest ROCAUC. An oral microbiome model including Lautropia, Streptococcus and Bacteroidetes showed the greatest discrimination between Barrette’s Esophagus and controls vs Lautropia alone.IMPLICATIONS FOR PATIENT CAREPrior studies identified significant multiOmic, multi-compartmental non-invasive biomarker risks for GERD and its complications such as BE. However, due to study limitations and to further ascertain the reliability, accuracy and clinical utility of these biomarkers more studies are warranted.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and rapidly led to a global pandemic that affected 213 countries, more than 5.8 million cases, and 360,000 deaths worldwide as of May 28, 2020. The United States currently has the highest number of COVID-19 cases in the world and contributes to nearly a third of the global death rate. The prevalence of COVID myocarditis is unclear but generally considered rare, with estimates up to 7% of COVID-related deaths. However, these patients suffered catastrophic worsening disease with respiratory compromise requiring intubation and often death. We report the case of a patient with COVID-19-induced myocarditis who was successfully treated with dexamethasone and review the literature.

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-PET), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flow-velocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M post-exposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after PM-exposure. Similarly, α-smooth muscle actin(α-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. Our study shows persistent WTC-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after PM exposure. Early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets.

To describe the exclusion criteria and risk-adjustment model developed for the quality measure Change in Self-Care. The exclusion criteria and risk adjustment model are used to calculate Change in Self-Care scores, allowing scores to be compared across inpatient rehabilitation facilities (IRFs).This national cohort study examined admission demographic and clinical factors associated with IRF patients' self-care change scores using standardized self-care data for Medicare patients discharged in calendar year 2017.A total of 1129 IRFs in the United States.A total of 493,209 (N=493,209) Medicare Fee-for-Service and Medicare Advantage IRF patient stays INTERVENTIONS: Not applicable.Self-care change scores using admission and discharge standardized assessment data elements from the Inpatient Rehabilitation Facility-Patient Assessment Instrument.Approximately 53% of patients were female, and 67% were between 65 and 84 years old. The final risk-adjustment model contained 93 clinically relevant risk adjusters and explained 23.1% of variance in self-care change scores. Risk adjusters that had the greatest effect on change scores and included IRF primary diagnosis group (ie, binary risk adjusters representing 13 diagnoses), prior self-care functioning, and age older than 90 years. When split by deciles of expected scores, the ratio of the average expected and observed change scores was within 2% of 1.0 across 8 groups and within 8% at the extremes, showing good predictive accuracy.The risk adjustment model quantifies the relationship between IRF patients' demographic and clinical characteristics and their self-care score changes. The exclusion criteria and model are used to risk-adjust the IRF Change in Self-Care quality measure.

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM

Biomarkers predict World Trade Center-Lung Injury (WTC-LI); however, there remains unaddressed multicollinearity in our serum cytokines, chemokines, and high-throughput platform datasets used to phenotype WTC-disease. To address this concern, we used automated, machine-learning, high-dimensional data pruning, and validated identified biomarkers. The parent cohort consisted of male, never-smoking firefighters with WTC-LI (FEV1, %Pred< lower limit of normal (LLN); n = 100) and controls (n = 127) and had their biomarkers assessed. Cases and controls (n = 15/group) underwent untargeted metabolomics, then feature selection performed on metabolites, cytokines, chemokines, and clinical data. Cytokines, chemokines, and clinical biomarkers were validated in the non-overlapping parent-cohort via binary logistic regression with 5-fold cross validation. Random forests of metabolites (n = 580), clinical biomarkers (n = 5), and previously assayed cytokines, chemokines (n = 106) identified that the top 5% of biomarkers important to class separation included pigment epithelium-derived factor (PEDF), macrophage derived chemokine (MDC), systolic blood pressure, macrophage inflammatory protein-4 (MIP-4), growth-regulated oncogene protein (GRO), monocyte chemoattractant protein-1 (MCP-1), apolipoprotein-AII (Apo-AII), cell membrane metabolites (sphingolipids, phospholipids), and branched-chain amino acids. Validated models via confounder-adjusted (age on 9/11, BMI, exposure, and pre-9/11 FEV1, %Pred) binary logistic regression had AUCROC [0.90(0.84–0.96)]. Decreased PEDF and MIP-4, and increased Apo-AII were associated with increased odds of WTC-LI. Increased GRO, MCP-1, and simultaneously decreased MDC were associated with decreased odds of WTC-LI. In conclusion, automated data pruning identified novel WTC-LI biomarkers; performance was validated in an independent cohort. One biomarker—PEDF, an antiangiogenic agent—is a novel, predictive biomarker of particulate-matter-related lung disease. Other biomarkers—GRO, MCP-1, MDC, MIP-4—reveal immune cell involvement in WTC-LI pathogenesis. Findings of our automated biomarker identification warrant further investigation into these potential pharmacotherapy targets., Author summary Disease related to air pollution causes millions of deaths annually. Large swathes of the general population, as well as certain occupations such as 1st responders and military personnel, are exposed to particulate matter (PM)—a major component of air pollution. Our longitudinal cohort of FDNY firefighters exposed to the World Trade Center dust cloud on 9/11 is a unique research opportunity to characterize the impact of a single, intense PM exposure by looking at pre- and post-exposure phenotype; however, PM-related lung disease and PM’s systemic effects are complex and call for a systems biological approach coupled with novel computational modelling techniques to fully understand pathogenesis. In the present study, we integrate clinical and environmental biomarkers with the serum metabolome, cytokines, and chemokines to develop a model for early disease detection and identification of potential signaling cascades of PM-related chronic lung disease.

Background Metabolic syndrome (MetSyn) predicted future development of World Trade Center lung injury (WTC-LI) in a subgroup of firefighters who never smoked and were male. An intracohort validation of MetSyn as a predictor of WTC-LI is examined in the cohort exposed to the World Trade Center (WTC) that has been followed longitudinally for 16 years. Methods Results of pulmonary function tests (n = 98,221) in workers exposed to the WTC (n = 9,566) were evaluated. A baseline cohort of firefighters who had normal FEV1 before 9/11 and who had had serum drawn before site closure on July 24, 2002 (n = 7,487) was investigated. Case subjects with WTC-LI (n = 1,208) were identified if they had at least two measured instances of FEV1 less than the lower limit of normal (LLN). Cox proportional hazards modeled early MetSyn biomarker ability to predict development of FEV1 less than the LLN. Results Case subjects were more likely to smoke, be highly exposed, and have MetSyn. There was a significant exposure dose response; the individuals most highly exposed had a 30.1% increased risk of developing WTC-LI, having MetSyn increased risk of developing WTC-LI by 55.7%, and smoking increased risk by 15.2%. There was significant interaction between smoking and exposure. Conclusions We validated the usefulness of MetSyn to predict future WTC-LI in a larger population of individuals who were exposed. MetSyn defined by dyslipidemia, insulin resistance, and cardiovascular disease suggests that systemic inflammation can contribute to future lung function loss.

RATIONALE The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 2019 (COVID-19), a new infectious disease, for which there are currently limited treatments. SARS-CoV-2 emerged in Wuhan, China in late 2019 and has expanded into a pandemic, which was declared on March 20, 2020. The United States (US) reported its first confirmed case on January 12, 2020, it has become the country with the greatest number of both cumulative and active COVID-19 cases. As of December 20, 2020, the US has over 17.9 million cases. As of April 11, 2020, the state of New York was the epicenter of the global health emergency with more confirmed cases of COVID-19 then any country worldwide. New York. Biomarkers have been studied in the context of COVID-19, but there have only been a few studies of a limited population. COVID-19 is a resource intensive disease with a high mortality. Therefore, being able to define predictive/associated biomarkers may not only facilitate early diagnosis of presumptive COVID, but also provide guidelines for early aggressive treatment and acuity of care triage.METHODS We examined all patients, admitted the MICU and adult medicine service for confirmed positive cases COVID or presumed COVID admitted to the Manhattan and Brooklyn campuses of our institution in the first 60 days of the COVID-19 pandemic, March 1-April 30, 2020. Our natural history study was accomplished by the review of the electronic medical records (EMR) of those diagnosed with COVID-19. Subjects were examined from the time of admission to discharge from each of the participating institutions. All data was collected in compliance with the Code of Federal Regulations, Title 21, Part 11 and approved by the NYU IRB#20-00473.RESULTS Of the N=13,307 COVID-19 positive patients admitted, N=4136 were of Hispanic/Latino descent, and N=932 were admitted to the ICU. The cohort was followed longitudinally with serial labs including inflammatory markers: d-dimers, ferritin, IL-1, IL-6, and CRP. Peak d-dimer, ferritin, and IL-6 was significantly associated with ICU admission (p

RATIONALE. Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China in late 2019 and has expanded into a global pandemic. This mass casualty triage, while requiring tremendous resources, also required early decision-making and ultimately allocation of critical care resources. Primary Objective was to ascertain risk factors of COVID-19 patients requiring ICU admission. Identify biomarkers, clinical risk factors, and comorbid conditions that can predict clinical outcome. METHODS. Setting and Study Design. We performed a natural history/retrospective chart review of patient admissions (n=5,568) at our facility for patients admitted between March 1-May 1, 2020, over 18 years of age, with a positive test less than 15 days before admission. We examined their inflammatory biomarker profile and clinical phenotype collected as part of their standard of care (n=90 variables). Analysis. Random forests used as a variable selector were assessed via a modified hamming distance between variable importance rankings of models with identical hyperparameters. The top 10% of variables (n=9) by mean decrease accuracy (MDA) were then included in a gradient-boosted tree model (xgboost package, R-Project) to build classifiers of ICU admissions and mortality. A random hyperparameter space search determined a final model that maximized 5-fold cross-validated AUCROC. All data was collected in compliance with the Code of Federal Regulations, Title 21, Part 11 and approved by the NYU IRB#20-00473. RESULTS. The classifiers of ICU admission and mortality had AUCROC = 0.93 and 0.90, and classification error = 15.6% and 20.2% based on the Youden's index-optimal probability threshold, respectively. Variables in the final predictive models of ICU admission and mortality are shown by rank (by MDA) in each model, with rank of 1 being the most important, Figure 1. In predicting ICU admission, the three most important variables were triglycerides, procalcitonin, and c-reactive protein;age, initial O2 flow (L/min), and blood O2 saturation were the three most important predictors of mortality. Procalcitonin, blood O2 saturation, lactate, and initial O2 flow (L/min) were predicted both ICU admission and mortality. CONCLUSION. Our models will be included in an online calculator that will be made available and can be used at point of care by providers to assist risk assessment and triage. Our analysis suggests that novel biomarker combinations may be important in assessment of COVID-19 severity. Future work will include validation of these models in other populations.

Background Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD. Methods WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV1 Results N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. Conclusions REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV1). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI). We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI &gt, 27 kg/m2 will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)&mdash, an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions, or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV1, fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease.

World Trade Center particulate matter (WTC-PM)-exposed firefighters with metabolic syndrome (MetSyn) have a higher risk of WTC lung injury (WTC-LI). Since macrophages are crucial innate pulmonary mediators, we investigated WTC-PM/lysophosphatidic acid (LPA) co-exposure in macrophages. LPA, a low-density lipoprotein metabolite, is a ligand of the advanced glycation end-products receptor (AGER or RAGE). LPA and RAGE are biomarkers of WTC-LI. Human and murine macrophages were exposed to WTC-PM, and/or LPA, and compared to controls. Supernatants were assessed for cytokines/chemokines, cell lysate immunoblots were assessed for signaling intermediates after 24 h. To explore the translatability of our in-vitro findings, we assessed serum cytokines/chemokines and metabolites of symptomatic, never-smoking WTC-exposed firefighters. Agglomerative hierarchical clustering identified phenotypes of WTC-PM-induced inflammation. WTC-PM induced GM-CSF, IL-8, IL-10, and MCP-1 in THP-1-derived macrophages and induced IL-1&alpha, IL-10, TNF-&alpha, and NF-&kappa, B in RAW264.7 murine macrophage-like cells. Co-exposure induced synergistic elaboration of IL-10 and MCP-1 in THP-1-derived macrophages. Similarly, co-exposure synergistically induced IL-10 in murine macrophages. Synergistic effects were seen in the context of a downregulation of NF-&kappa, B, p-Akt, -STAT3, and -STAT5b. RAGE expression after co-exposure increased in murine macrophages compared to controls. In our integrated analysis, the human cytokine/chemokine biomarker profile of WTC-LI was associated with discriminatory metabolites (fatty acids, sphingolipids, and amino acids). LPA synergistically elaborated WTC-PM&rsquo, s inflammatory effects in vitro and was partly RAGE-mediated. Further research will focus on the intersection of MetSyn/PM exposure.

Pulmonary disease after World Trade Center particulate matter (WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We used a murine model and a multiomics assessment to understand the role of RAGE in the pulmonary long-term effects of a single high-intensity exposure to WTC-PM. After 1 month, WTC-PM–exposed wild-type (WT) mice had airway hyperreactivity, whereas RAGE-deficient (Ager(−/−)) mice were protected. PM-exposed WT mice also had histologic evidence of airspace disease, whereas Ager(−/−) mice remained unchanged. Inflammatory mediators such as G-CSF (granulocyte colony–stimulating factor), IP-10 (IFN-γ–induced protein 10), and KC (keratinocyte chemoattractant) were differentially expressed after WTC-PM exposure. WTC-PM induced α-SMA, DIAPH1 (protein diaphanous homolog 1), RAGE, and significant lung collagen deposition in WT compared with Ager(−/−) mice. Compared with WT mice with PM exposure, relative expression of phosphorylated to total CREB (cAMP response element–binding protein) and JNK (c-Jun N-terminal kinase) was significantly increased in the lung of PM-exposed Ager(−/−) mice, whereas Akt (protein kinase B) was decreased. Random forests of the refined lung metabolomic profile classified subjects with 92% accuracy; principal component analysis captured 86.7% of the variance in three components and demonstrated prominent subpathway involvement, including known mediators of lung disease such as vitamin B(6) metabolites, sphingolipids, fatty acids, and phosphatidylcholines. Treatment with a partial RAGE antagonist, pioglitazone, yielded similar fold-change expression of metabolites (N(6)-carboxymethyllysine, 1-methylnicotinamide, N(1)+N(8)-acetylspermidine, and succinylcarnitine [C4-DC]) between WT and Ager(−/−) mice exposed to WTC-PM. RAGE can mediate WTC-PM–induced airway hyperreactivity and warrants further investigation.

Zika virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Roughly 60% of people in countries such as the U.S. live in areas at risk for seasonal spread of ZIKV. ZIKV belongs to a class of diseases that is not typically seen in hospital settings across the U.S. and Europe. We describe the case presentation, management, and treatment of ZIKV infection complicated by GBS. A 64-year-old woman with recent travel to the Dominican Republic presented with rash followed by an acute, ascending polyneuropathy consistent with GBS. She was confirmed to have an acute ZIKV infection by detection of ZIKV nucleic acid by reverse transcription-polymerase chain reaction. She met Brighton Collaboration criteria level 1 evidence for GBS. She received two courses of intravenous immunoglobulin and slowly improved, though still had weakness at discharge. More research is needed to identify the pathophysiology behind ZIKV-associated GBS and its optimal treatment. Prevention is fundamental to limiting infection and spread of ZIKV.

Background In clinical practice, do-not-intubate (DNI) orders are generally accompanied by do-not-resuscitate (DNR) orders. Use of do-not-resuscitate (DNR) orders is associated with older patient age, more comorbid conditions, and the withholding of treatments outside of the cardiac arrest setting. Previous studies have not unpacked the factors independently associated with DNI orders. Objective To compare factors associated with combined DNR/DNI orders versus isolated DNR orders, as a means of elucidating factors associated with the addition of DNI orders. Design Retrospective chart review. Setting/subjects Patients who died on a General Medicine or MICU service (n = 197) at an urban public hospital over a 2-year period. Measurements Logistic regression was used to identify demographic and medical data associated with code status. Results Compared with DNR orders alone, DNR/DNI orders were associated with a higher median Charlson Comorbidity Index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.13–1.43); older age (OR 1.02, 95% CI 1.01–1.04); malignancy (OR 2.27, 95% CI 1.18–4.37); and female sex (OR 1.98, 95% CI 1.02–3.87). In the last 3 days of life, they were associated with morphine administration (OR 2.76, 95% CI 1.43–5.33); and negatively associated with use of vasopressors/inotropes (OR 10.99, 95% CI 4.83–25.00). Conclusions Compared with DNR orders alone, combined DNR/DNI orders are more strongly associated with many of the same factors that have been linked to DNR orders. Awareness of the extent to which the two directives may be conflated during code status discussions is needed to promote patient-centered application of these interventions.

Gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE), which are prevalent in the World Trade Center (WTC) exposed and general populations, negatively impact quality of life and cost of healthcare. GERD, a risk factor of BE, is linked to obstructive airways disease (OAD). We aim to identify serum biomarkers of GERD/BE, and assess the respiratory and clinical phenotype of a longitudinal cohort of never-smoking, male, WTC-exposed rescue workers presenting with pulmonary symptoms. Biomarkers collected soon after WTC-exposure were evaluated in optimized predictive models of GERD/BE. In the WTC-exposed cohort, the prevalence of BE is at least 6 times higher than in the general population. GERD/BE cases had similar lung function, D LCO , bronchodilator response and long-acting β-agonist use compared to controls. In confounder-adjusted regression models, TNF-α ≥ 6 pg/mL predicted both GERD and BE. GERD was also predicted by C-peptide ≥ 360 pg/mL, while BE was predicted by fractalkine ≥ 250 pg/mL and IP-10 ≥ 290 pg/mL. Finally, participants with GERD had significantly increased use of short-acting β-agonist compared to controls. Overall, biomarkers sampled prior to GERD/BE presentation showed strong predictive abilities of disease development. This study frames future investigations to further our understanding of aerodigestive pathology due to particulate matter exposure.

We present a case of severe symptomatic hyponatremia (94 mEq/L) in a male patient who presented with nausea, vomiting, and multiple falls. The patient was found with symptomatic hypo-osmolar hypovolemic hyponatremia secondary to volume loss from vomiting, diuretic use, and consumption of solute-free water. To manage such a severely hyponatremic patient, concomitant 3% hypertonic saline and DDAVP were initiated with successful slow and sustained correction of sodium without complications of osmotic demyelination syndrome.

OBJECTIVES/GOALS: Metabolic syndrome (MetSyn) is a risk for World Trade Center-Lung Injury (WTC-LI; defined as developing FEV11 LLN (N = 5,746). Data assessed from last pre-9/11 till August 1, 2017. Longitudinal MetSyn characteristics were assessed using 3 models: i. A linear mixed effect model to assess the effect size of longitudinal MetSyn and its components on longitudinal FEV1% predicted as an outcome; ii. a time-dependent Cox regression to assess the associations of MetSyn to time of onset of WTC-LI; iii. a novel, partially linear single index regression model with repeatedly measured MetSyn to assess their joint effects and delineate their relative contribution on the longitudinal lung function in the WTC-FDNY cohort. RESULTS/ANTICIPATED RESULTS: In Model I, BMI 30 kg/m2 had the largest effect size compared to ever-smoking, with −2.524 (95%CI: −2.708,−2.340) compared to −1.681(−2.325,−1.038) respectively. Having MetSyn, defined as 3/5 risk factors, had an effect size of −2.319(−2.526,−2.112). In Model II, hazards of triglycerides 150mg/dL were highest at 1.497(1.336, 1.677), followed by BMI 30 kg/m2 at 1.406(1.256, 1.575), and HDLModel III The proposed methods will be applied to our cohort study. DISCUSSION/SIGNIFICANCE OF IMPACT: MetSyn is both a predictor and concurrent marker of WTC-LI. The single index model can not only reduce dimensionality of the covariates, but also provides efficient estimates of the joint MetSyn effects, allowing linear or nonlinear effects. Future studies will investigate dietary intervention as a potential disease-modifying factor. CONFLICT OF INTEREST DESCRIPTION: NA, nothing to disclose.

Particulate matter (PM) exposure is associated with the development of cardiopulmonary disease. Our group has studied the adverse health effects of World Trade Center particulate matter (WTC-PM) exposure on firefighters. To fully understand the complex interplay between exposure, organism, and resultant disease phenotype, it is vital to analyze the underlying role of genomics in mediating this relationship. A PubMed search was performed focused on environmental exposure, genomics, and cardiopulmonary disease. We included original research published within 10 years, on epigenetic modifications and specific genetic or allelic variants. The initial search resulted in 95 studies. We excluded manuscripts that focused on work-related chemicals, heavy metals and tobacco smoke as primary sources of exposure, as well as reviews, prenatal research, and secondary research studies. Seven full-text articles met pre-determined inclusion criteria, and were reviewed. The effects of air pollution were evaluated in terms of methylation (n = 3), oxidative stress (n = 2), and genetic variants (n = 2). There is evidence to suggest that genomics plays a meditating role in the formation of adverse cardiopulmonary symptoms and diseases that surface after exposure events. Genomic modifications and variations affect the association between environmental exposure and cardiopulmonary disease, but additional research is needed to further define this relationship.