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Light’s criteria is the standard for determining the etiology of pleural effusions. Test characteristics of Light’s criteria varies in different populations, and Light’s criteria may misclassify effusions in patients with impaired immunity such as in neutropenia. This study evaluates the test characteristics of Light’s criteria and other clinically available pleural fluid tests in a cohort of patients with neutropenia. Cases were defined as a thoracentesis performed with an absolute neutrophil count of less than 1000 cells/µl documented at least 24 hours prior to the procedure. The etiology of the effusion was adjudicated by independent review of the case data and hospital course by two board certified pulmonologists. Categories for final diagnosis included exudate due to infection, exudate due to malignancy, exudate due to other, and transudate. A total of 83 thoracenteses from 80 patients were identified. Comorbidities included hematologic and solid tumor malignancies, recipients of allogeneic stem cell and solid organ transplants, heart failure, chronic kidney disease, and decompensated cirrhosis. Light’s criteria had a sensitivity of 92% and a specificity of 55% for identifying exudates, LR+ 2.07 and LR-0.14. A pleural fluid protein value of >2.9 g/dl had a sensitivity of 42% and a specificity of 96%, LR+11.12 and LR-0.61. When comparing exudative effusions, the percentage of neutrophils in the pleural fluid was significantly higher in infection, despite peripheral neutropenia. Together these results show a reduced specificity of Light’s criteria in neutropenia, and underscore the complexity of pleural effusions in this setting.

Distributive shock is a major cause of morbidity and mortality in the ICU. IV fluid resuscitation is a vital intervention to improve cardiac output and end-organ perfusion during the initial resuscitation and for those who remain fluid responsive. Noninvasive measures of fluid responsiveness are lacking. The aim of this study is to assess whether changes in end-tidal coSingle-center prospective study.Patients were enrolled from 2019 to 2021 from the medical ICU within a single academic hospital.Thirty-eight patients with paired measurements of fluid responsiveness as determined by bioreactance who were admitted to the ICU with a diagnosis of distributive shock and on mechanical ventilation.Stroke volume index (SVI), cardiac index, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and ETcoThe sensitivity and specificity of a ΔETcoA ΔETco

RationaleContribution of central lung tissues to pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unknown.ObjectiveTo ascertain the relationship between cell types of IPF-central and IPF-peripheral lung explants using RNA sequencing (RNA-seq) transcriptome.MethodsBiopsies of paired IPF-central and IPF-peripheral along with non-IPF lungs were selected by reviewing H&E data. Criteria for differentially expressed genes (DEG) were set at false discovery rate 2. Computational cell composition deconvolution was performed. Signature scores were computed for each cell type.FindingsComparison of central IPF versus non-IPF identified 1723 DEG (1522 upregulated and 201 downregulated). Sixty-two per cent (938/1522) of the mutually upregulated genes in central IPF genes were also upregulated in peripheral IPF versus non-IPF. Moreover, 85 IPF central-associated genes (CAG) were upregulated in central IPF versus both peripheral IPF and central non-IPF. IPF single-cell RNA-seq analysis revealed the highest CAG signature score in myofibroblasts and significantly correlated with a previously published activated fibroblasts signature (r=0.88, p=1.6×10−4). CAG signature scores were significantly higher in IPF than in non-IPF myofibroblasts (p=0.013). Network analysis of central-IPF genes identified a module significantly correlated with the deconvoluted proportion of myofibroblasts in central IPF and anti-correlated with inflammation foci trait in peripheral IPF. The module genes were over-represented in idiopathic pulmonary fibrosis signalling pathways.InterpretationGene expression in central IPF lung regions demonstrates active myofibroblast features that contributes to disease progression. Further elucidation of pathological transcriptomic state of cells in the central regions of the IPF lung that are relatively spared from morphological rearrangements may provide insights into molecular changes in the IPF progression.

Rationale: Disease activity in idiopathic pulmonary fibrosis (IPF) remains highly variable, poorly understood, and difficult to predict. Objectives: To identify a predictor using short-term longitudinal changes in gene expression that forecasts future FVC decline and to characterize involved pathways and cell types. Methods: Seventy-four patients from COMET (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in IPF) cohort were dichotomized as progressors (≥10% FVC decline) or stable. Blood gene-expression changes within individuals were calculated between baseline and 4 months and regressed with future FVC status, allowing determination of expression variations, sample size, and statistical power. Pathway analyses were conducted to predict downstream effects and identify new targets. An FVC predictor for progression was constructed in COMET and validated using independent cohorts. Peripheral blood mononuclear single-cell RNA-sequencing data from healthy control subjects were used as references to characterize cell type compositions from bulk peripheral blood mononuclear RNA-sequencing data that were associated with FVC decline. Measurements and Main Results: The longitudinal model reduced gene-expression variations within stable and progressor groups, resulting in increased statistical power when compared with a cross-sectional model. The FVC predictor for progression anticipated patients with future FVC decline with 78% sensitivity and 86% specificity across independent IPF cohorts. Pattern recognition receptor pathways and mTOR pathways were downregulated and upregulated, respectively. Cellular deconvolution using single-cell RNA-sequencing data identified natural killer cells as significantly correlated with progression. Conclusions: Serial transcriptomic change predicts future FVC decline. An analysis of cell types involved in the progressor signature supports the novel involvement of natural killer cells in IPF progression.

BackgroundAcute pulmonary embolism remains a significant cause of mortality and morbidity worldwide. Benefit of recently developed multidisciplinary PE response teams (PERT) with higher utilization of advanced therapies has not been established.MethodsTo evaluate patient-centered outcomes and cost-effectiveness of a multidisciplinary PERT we performed a retrospective analysis of 554 patients with acute PE at the university of Virginia between July 2014 and June 2015 (pre-PERT era) and between April 2017 through October 2018 (PERT era). Six-month survival, hospital length-of-stay (LOS), type of PE therapy, and in-hospital bleeding were assessed upon collected data.Results317 consecutive patients were treated for acute PE during an 18-month period following institution of a multidisciplinary PE program; for 120 patients PERT was activated (PA), the remaining 197 patients with acute PE were considered as a separate, contemporary group (NPA). The historical, comparator cohort (PP) was composed of 237 patients. These 3 groups were similar in terms of baseline demographics, comorbidities and risk, as assessed by the Pulmonary Embolism Severity Index (PESI). Patients in the historical cohort demonstrated worsened survival when compared with patients treated during the PERT era. During the PERT era no statistically significant difference in survival was observed in the PA group when compared to the NPA group despite significantly higher severity of illness among PA patients. Hospital LOS was not different in the PA group when compared to either the NPA or PP group. Hospital costs did not differ among the 3 cohorts. 30-day re-admission rates were significantly lower during the PERT era. Rates of advanced therapies were significantly higher during the PERT era (9.1% vs. 2%) and were concentrated in the PA group (21.7% vs. 1.5%) without any significant rise in in-hospital bleeding complications.ConclusionsAt our institution, all-cause mortality in patients with acute PE has significantly and durably decreased with the adoption of a PERT program without incurring additional hospital costs or protracting hospital LOS. Our data suggest that the adoption of a multidisciplinary approach at some institutions may provide benefit to select patients with acute PE.

Nonurgent commercial air travel in patients who have experienced a nonhemorrhagic cerebrovascular accident (CVA) may occur, particularly in the elderly traveling population. A recent CVA, particularly occurring during a person's travel, presents a significant challenge to the patient, companions, family, and health care team. Specific medical recommendation, based on accumulated scientific data and interpreted by medical experts, is needed so that travel health care professionals can appropriately guide the patient. Unfortunately, such recommendations are almost entirely lacking despite the relative frequency of CVA and air travel. This article reviews the existing recommendations with conclusions based on both these limited data and rationale conjecture.

Abdominal aortic aneurysm (AAA) presents across a spectrum of severity. Although some resources suggest a theoretic risk for rupture related to air travel, this claim remains unproven. In fact, there are little data from which to make evidence-based recommendations. Air medical evacuation of a patient with either an AAA at risk of imminent rupture or status post recent rupture can be performed, assuming that local surgical care is not available and that transfer is taking the patient to a higher level of medical intervention. Furthermore, medical opinion suggests that patients with asymptomatic and/or surgically corrected AAA can safely travel by commercial aircraft for nonurgent reasons, assuming that other issues including postoperative needs are appropriately addressed. In this discussion, answers to the following issues are sought: flight safety for urgent evacuation and nonurgent repatriation scenarios, waiting time to fly nonurgently after AAA diagnosis, and the need for medical accompaniment.

The electrocardiographic (ECG) diagnosis of ST-segment elevation myocardial infarction (STEMI) represents a challenge to all health care providers, particularly so for the novice ECG interpreter. We have developed—and present in this article—a 4-step algorithm that will detect STEMI in most instances in the prehospital and other nonemergency department (ED) settings. The algorithm should be used in adult patients with chest pain or equivalent presentation who are suspected of STEMI. It inquires as to the presence of ST-segment elevation as well as the presence of STEMI confounding/mimicking patterns; the algorithm also makes use of reciprocal ST-segment depression as an adjunct in the ECG diagnosis of STEMI. If STEMI is detected by this algorithm, then management decisions can be made based upon this ECG diagnosis. If STEMI is not detected using this algorithm, then we can only note that STEMI is not “ruled in”; importantly, STEMI is not “ruled out.” In fact, more expert interpretation of the ECG will be possible once the patient (and/or the ECG) arrive in the ED where ECG review can be made with the more complex interpretation used by expert physician interpreters.