Abstract: Accurate assessment of prognosis in idiopathic pulmonary fibrosis (IPF) remains elusive due to significant individual radiologic and physiologic variability. We hypothesized that short term radiologic changes may be predictive of survival.We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Lab at Mayo Clinic, for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography (HRCT). We assessed baseline and follow-up (time point 1 and 2, respectively) HRCT scans in 55 selected IPF patients and correlated CALIPER-quantified measurements with expert radiologists' assessments and clinical outcomes.Findings of interval change (mean 289 days) in volume of reticular densities (HR 1.91, P=0.006), total volume of interstitial abnormalities (HR 1.70, P=0.003) and percent total interstitial abnormalities (HR 1.52, P=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short term global ILD progression but not specific radiologic features was also predictive of mortality.These data demonstrate the feasibility of quantifying interval short term changes on HRCT and their possible use as independent predictors of survival in IPF.
Abstract: Progressive multifocal leukoencephalopathy (PML) is associated with JC polyomavirus (JCV) infection of central nervous system oligodendrocytes resulting in demyelinization and progressive focal neurologic deficits. Reactivation of dormant JCV occurs in the setting of immunosuppression, most commonly in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or hematological malignancies. PML has also been reported in solid organ transplant recipients. We report the case of a 61-year-old man after bilateral lung transplantation for chronic hypersensitivity pneumonitis who presented with leg weakness, cognitive decline, and expressive aphasia at 5Â months post transplantation. Magnetic resonance imaging and brain biopsy were consistent with PML. Treatment attempt with cytarabine was unsuccessful, and immunomodulation resulted in recurrent grade A3 rejection. The difficulty of managing PML in lung transplant patients is highlighted by the lack of directed therapy and risk of graft rejection or failure with attempts at decreasing immunosuppression.
Abstract: The objective of this study was to assess the frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension (IPAH) and describe the correlative clinical features.
Abstract: Pneumocystis species are opportunistic fungal organisms that cause severe pneumonia in immune-compromised hosts, with resultant high morbidity and mortality. Recent work indicates that IL-17 responses are important components of host defense against fungal pathogens. In the present study, we demonstrate that cell-surface β-glucan components of Pneumocystis (PCBG) stimulate human dendritic cells (DCs) to secrete IL-23 and IL-6. These cytokines are well established to stimulate a T helper-17 (Th17) phenotype. Accordingly, we further observe that PCBG-stimulated human DCs interact with lymphocytes to drive the secretion of IL-17 and IL-22, both Th17-produced cytokines. The activation of DCs was shown to involve the dectin-1 receptor with a downstream activation of the Syk kinase and subsequent translocation of both the canonical and noncanonical components of the NF-κB transcription factor family. Finally, we demonstrate that glycosphingolipid-rich microdomains of the plasma membrane participate in the activation of DCs by PCBG through the accumulation of lactosylceramide at the cell surface during stimulation with PCBG. These data strongly support the idea that the β-glucan surface components of Pneumocystis drive the activation of the IL-23/IL-17 axis during this infection, through a glycosphingolipid-initiated mechanism.
Abstract: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis.
Abstract: Small cell lung cancer (SCLC) is considered an inappropriate screening target due to its short preclinical phase and high rate of relapse despite optimal therapy. However, while intuitively screening for SCLC is inadvisable, in reality, there is a scarcity of data focusing on screen-detected SCLC and whether this intervention leads to diagnosis at an earlier clinical stage or alters outcome.
Abstract: While the combination of a patent foramen ovale (PFO) and thromboembolic disease is thought to portend increased morbidity and mortality, PFO presence in the setting of major pulmonary embolism (PE) may serve as a means to rescue patients from immediate hemodynamic collapse and death. We present two patients with major pulmonary embolism and right-to-left shunting consistent with PFO as seen on transthoracic echocardiography. In the setting of major PE, PFO may prevent acute right ventricular failure by acting as a 'pop-off' valve, alleviating increased ventricular pressures; but concomitantly portend deleterious effects in the form of paradoxical embolism and intractable hypoxemia.
Abstract: Dyspnea in patients with known chronic obstructive pulmonary disease (COPD) can be a clinical challenge due to the nonspecific nature of atypical presentations. Typical features of fever, productive cough, and wheezing on presentation support COPD exacerbation, while absence of such findings may warrant further evaluation for underlying etiologies, including pulmonary embolism (PE). It is suspected that one in four patients with atypical COPD exacerbation may have PE as an underlying or concomitant cause of acute dyspnea. This review discusses the clinical presentation of COPD and PE, and presents an overview of the rationale for pursuing work-up for thromboembolic disease in the setting of known obstructive lung diseases.
