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Background: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. Methods: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit–level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit–level COVID-19 rates. Results: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08–3.55]; P =0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32–0.99]; P =0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose ( P =0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P =0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56–1.48]; P =0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. Conclusions: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04409834.

Background Secondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. Methods This was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 hours after admission. Results Thirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3-0.5) versus 0.6 K/uL (IQR 0.3-0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p=0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p=0.01] and D-dimer (18.5 mg/L vs. 1.4 mg/L, p

BACKGROUND: Bronchoscopy is an aerosol-generating procedure and routine use for patients with coronavirus disease 2019 (COVID-19) has been discouraged. The purpose of this review was to discuss the indications, clinical utility, and risks associated with bronchoscopy in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: A literature search was performed by using appropriate key terms to identify all relevant articles from medical literature databases up to August 1, 2021. RESULTS: Twelve cohorts (9 retrospective and 3 prospective) reported the performance of 2,245 bronchoscopies in 1,345 patients with COVID-19. The majority of the subjects were male. Nearly two thirds of the bronchoscopies (62%) were performed for therapeutic indications; the rest (38%) were for diagnostic purposes. Bronchoalveolar lavage had an overall yield of 33.1% for SARS-CoV-2 in subjects with negative results of real-time polymerase chain reaction on nasopharyngeal specimens. The incidence of a secondary infection ranged from 9.3% to as high as 65%. Antibiotics were changed in a significant number of the subjects (14%–83%) based on the bronchoscopic findings. Bronchoscopy was well tolerated in most subjects except those who required noninvasive ventilation, in whom the intubation rate after the procedure was 60%. The rate of transmission of SARS-CoV-2 among health-care workers was minimum. CONCLUSIONS: Bronchoscopy in patients with COVID-19 results in a significant change in patient management. Transmission of SARS-CoV-2 seems to be low with consistent use of appropriate personal protective equipment by health-care workers. Therefore, bronchoscopic evaluation should be considered for all diagnostic and therapeutic indications in this patient population.

Antisynthetase syndrome (AS) is a rare disease that affects patients with inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM). In patients with AS, up to 95% of patients develop antisynthetase syndrome-associated interstitial lung disease (AS-ILD). Although AS-ILD commonly occurs in patients with a well-established diagnosis of AS, it can be the first or only manifestation of an occult AS. The frequency of interstitial lung disease (ILD), myopathy, and skin involvement are often dependent on the type of myositis-specific antibodies present. AS-ILD patients who are positive for both anti-Jo-1 and anti-SSA/RO-52 autoantibodies often present with a severe degree of lung restriction on pulmonary function tests and radiologic imaging with an inadequate response toward immunosuppressive therapies. We describe a 65-year-old woman who presents with chronic dyspnea. She was initially diagnosed with corticosteroid-resistant cryptogenic organizing pneumonia based on the radiological findings on her CT chest. Her symptoms did not improve, and she suffered from intolerable corticosteroid-related side effects. Reviews of systems were positive for arthritis and Raynaud's phenomenon. She was found to have elevated inflammatory markers and autoantibodies such as anti-Jo-1, anti-RO-52, and anti-SSA. A diagnosis of AS-ILD resistant to corticosteroid therapy was made. Her lung function improved with combination therapy of mycophenolate and rituximab. Our case highlights that a detailed history and physical exam, compatible radiologic imaging, and autoantibodies are essential for the diagnosis of AS-ILD.

Background Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population. Methods This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (Dlco) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for Dlco and FVC; and the Composite Physiologic Index, based on % predicted values for Dlco, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score. Results Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10% decrease in % predicted). Conclusions Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF. Trial Registry ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov.

Type A aortic dissection is an uncommon cause of chest pain that carries a high morbidity and mortality rate. A previous history of hypertension and coronary artery bypass grating (CABG) are recognized risk factors for Type A aortic dissection. We present a case of an elderly man who presents with acute onset chest pain and was found to have an acute ruptured Type A aortic dissection that has a “saddle pulmonary embolism”‐like appearance on computed tomography (CT) imaging. We also describe the clinical, laboratory, and radiological workup done leading up to the diagnosis of Type A aortic dissection in the emergency setting.

Chronic, silent microaspiration is a common but underrecognized pathologic process in pulmonary medicine. The clinical presentation is variable and diagnosis can be challenging. We present the case of a 55-year-old woman with known emphysema, who was referred to us for progressive respiratory failure that was unresponsive to therapy. The patient had 9 hospital admissions in the preceding 5 months and was treated with multiple courses of antibiotics and systemic steroid therapy for a diagnosis of cryptogenic organizing pneumonia. The steroid therapy was complicated by 51 pounds of weight gain. She had conversational as well as profound exertional shortness of breath. Physical examination revealed a woman in moderate distress and bilateral diffuse wheezing and rhonchi. Computed tomography of the chest revealed areas of bronchocentric consolidation and bronchial wall thickening in the bilateral lower lobes. She underwent surgical lung biopsy and the histopathology was consistent with chronic aspiration pneumonia.

Background Hospitalizations are common among patients with idiopathic pulmonary fibrosis (IPF). We investigated the impact of hospitalizations on outcomes in patients with IPF. Methods The IPF-PRO Registry is an observational US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Associations between patient characteristics and hospitalization, and between hospitalization and mortality, were analyzed using Cox regression models. Results A total of 1002 patients with IPF were enrolled into the IPF-PRO Registry. Over a median follow-up time of 23.7 months (maximum: 67.0 months), 568 patients (56.7%) had at least one hospitalization. Of these patients, 319 (56.2%) had at least one respiratory-related hospitalization and 120 (21.1%) had at least one hospitalization with ventilatory support. Younger age (HR 0.68 [95% CI 0.55, 0.84] per 5-year increase for patients Conclusions Data from the IPF-PRO Registry demonstrate that hospitalizations are common among patients with IPF. The risk of mortality during hospitalization or within 90 days of discharge was high, particularly among patients who were hospitalized for a respiratory cause or received ventilatory support. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

BackgroundOpaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit SARS-CoV-2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe COVID-19 pneumonia. The objective of the study was to evaluate the effect of opaganib on supplemental oxygen requirements, time to hospital discharge and its safety in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen.MethodsThis Phase 2a, randomized, double-blind, placebo-controlled study was conducted between July and December 2020 in eight sites in the USA. Forty-two enrolled patients received opaganib (n=23) or placebo (n=19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of opaganib/placebo.ResultsThe relative decrease in total supplemental oxygen requirement from baseline to Day 14 was 61.6% in the opaganib versus 46.7% in the placebo arms. By Day 14, 50.0% of patients in the opaganib and 22.2% in the placebo group no longer required supplemental oxygen for at least 24 hours, while 86.4% and 55.6%, respectively, were discharged from hospital. The incidence of ≥ Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group.ConclusionsIn this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib required less supplementary oxygen and had earlier hospital discharge, with no safety concerns arising. These findings support further evaluation of opaganib in this population.SummaryUpon receiving opaganib, patients with COVID-19 pneumonia who were hospitalized and required supplemental oxygen showed symptomatic clinical improvement compared to placebo, with less supplemental oxygen requirement, resulting in earlier hospital discharge, and no safety concerns arising.

Objective This narrative review aims to provide a detailed overview of pleural abnormalities in patients with coronavirus disease 19 or COVID-19. Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is a novel beta coronavirus responsible for COVID-19. Although pulmonary parenchymal and vascular changes associated with COVID-19 are well established, pleural space abnormalities have not been the primary focus of investigations. Methods Narrative overview of the medical literature regarding pleural space abnormalities in COVID-19. The appropriate manuscripts were identified by searching electronic medical databases and by hand searching the bibliography of the identified papers. Pleural abnormalities on transverse and ultrasound imaging are discussed. The incidence, clinical features, pathophysiology, and fluid characteristics of pleural effusion are reviewed. Studies reporting pneumothorax and pneumomediastinum are examined to evaluate for pathogenesis and prognosis. A brief comparative analysis of pleural abnormalities among patients with COVID-19, severe acute respiratory syndrome (SARS), and Middle Eastern respiratory syndrome (MERS) has been provided. Conclusions Radiologic pleural abnormalities are common in COVID-19, but the incidence of pleural effusion appears to be low. Pneumothorax is rare and does not independently predispose the patient to worse outcomes. SARS-CoV-2 infects the pleural space; however, whether the pleural fluid can propagate the infection is unclear.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which diagnosis and management remain challenging. Defining the circulating proteome in IPF may identify targets for biomarker development. We sought to quantify the circulating proteome in IPF, determine differential protein expression between subjects with IPF and controls, and examine relationships between protein expression and markers of disease severity. Methods This study involved 300 patients with IPF from the IPF-PRO Registry and 100 participants without known lung disease. Plasma collected at enrolment was analysed using aptamer-based proteomics (1305 proteins). Linear regression was used to determine differential protein expression between participants with IPF and controls and associations between protein expression and disease severity measures (percent predicted values for forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide [DLco]; composite physiologic index [CPI]). Multivariable models were fit to select proteins that best distinguished IPF from controls. Results Five hundred fifty one proteins had significantly different levels between IPF and controls, of which 47 showed a |log2(fold-change)| > 0.585 (i.e. > 1.5-fold difference). Among the proteins with the greatest difference in levels in patients with IPF versus controls were the glycoproteins thrombospondin 1 and von Willebrand factor and immune-related proteins C-C motif chemokine ligand 17 and bactericidal permeability-increasing protein. Multivariable classification modelling identified nine proteins that, when considered together, distinguished IPF versus control status with high accuracy (area under receiver operating curve = 0.99). Among participants with IPF, 14 proteins were significantly associated with FVC % predicted, 23 with DLco % predicted, 14 with CPI. Four proteins (roundabout homolog-2, spondin-1, polymeric immunoglobulin receptor, intercellular adhesion molecule 5) demonstrated the expected relationship across all three disease severity measures. When considered in pathways analyses, proteins associated with the presence or severity of IPF were enriched in pathways involved in platelet and haemostatic responses, vascular or platelet derived growth factor signalling, immune activation, and extracellular matrix organisation. Conclusions Patients with IPF have a distinct circulating proteome and can be distinguished using a nine-protein profile. Several proteins strongly associate with disease severity. The proteins identified may represent biomarker candidates and implicate pathways for further investigation. Trial registration ClinicalTrials.gov (NCT01915511).

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem vasculitic disorder that predominantly affects medium- and small-sized blood vessels. EGPA belongs to a group of vasculitides known as anti-neutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Upper airway involvement is seen in all ANCA-associated vasculitides, but destructive upper airway disease has never been reported in patients with EGPA. We report the first case of erosive chondritis and saddle nose deformity in a 50-year-old patient suffering from EGPA.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a variable clinical course and high mortality. We used data from a large national US registry of patients with IPF to investigate relationships between patient characteristics, including markers of disease severity, and mortality. Methods The analysis cohort comprised patients enrolled in the IPF-PRO Registry from its inception on 5 June 2014 to 26 October 2017. The primary criterion for inclusion in this registry is that patients must be diagnosed or confirmed with IPF at the enrolling centre within 6 months. Associations between patient characteristics and markers of disease severity at enrolment and mortality outcomes were investigated using univariable, multivariable and adjustment models. Results Among 662 patients enrolled, 111 patients died or had a lung transplant over a follow-up period of 30 months. The probability of being free of both events at month 30 was 50.6% (95% CI: 40.0, 60.2). When patient characteristics and markers of disease severity were jointly examined in a multivariable analysis, oxygen use at rest (hazard ratio [HR] 2.44 [95% CI: 1.45, 4.10]), lower forced vital capacity (FVC) % predicted (HR 1.28 [95% CI: 1.10, 1.49] per 10% decrease) and diffusion capacity for carbon monoxide (DLco) % predicted (HR 1.25 [95% CI: 1.04, 1.51] per 10% decrease) were significantly associated with increased risk of death or lung transplant. The risk of death or lung transplant increased with increasing age in patients ≥62 years old (HR 1.18 [95% CI: 0.99, 1.40] per 5-year increase), and decreased with increasing age in patients

Pulmonary manifestations of connective tissue diseases (CTD) carry high morbidity and potential mortality, and the most serious pulmonary type is interstitial lung disease (ILD). Identifying and promptly intervening CTD-ILD with immune suppressor therapy will change the natural course of the disease resulting in survival improvement. Compared to idiopathic pulmonary fibrosis, the most common presentation of idiopathic interstitial pneumonia (IIP), CTD-ILD carries a better prognosis due to the response to immune suppressor therapy. Nonspecific interstitial pneumonia (NSIP) is the most common type of CTD-ILD that is different from the fibrotic classical presentation of IPF, known as usual interstitial pneumonia (UIP). An exception is rheumatoid arthritis that presents more frequently with UIP type. Occasionally, IPF may not have typical radiographic features of UIP, and a full assessment to differentiate IPF from CTD-ILD is necessary, including the intervention of a multidisciplinary team and the histopathology. Interstitial pneumonia with autoimmune features (IPAF) shows promising advantages to identify patients with ILD who have some features of a CTD without a defined autoimmune disease and who may benefit from immune suppressors. A composition of clinical, serological, and morphologic features in patients presenting with ILD will fulfill criteria for IPAF. In summary, the early recognition and treatment of CTD-ILD, differentiation from IPF-UIP, and identification of patients with IPAF fulfill the assessment by the clinician for an optimal care.

Sjogren's syndrome is an autoimmune connective tissue disease targeting the exocrine glands and frequently affecting the respiratory system. The pulmonary disease is the most important extra-glandular manifestation as it carries most of the morbidity and mortality. Typically, it affects the small airways ranging from mild to severe respiratory symptoms. The upper airways are also commonly involved, predisposing sinusitis to occur more frequently than in the normal population. Lymphocytic interstitial pneumonia was initially thought to be the prevailing parenchymal disease; however, multiple cohorts report non-interstitial pneumonia to be the most frequent subtype of interstitial lung disease. In the review of high-resolution computed tomography scans, cystic lesions are commonly found and associate with both the small airways and parenchymal disease. Under their presence, amyloidosis or lymphomas should be considered in the differential. Overall, Sjogren's syndrome has a higher risk for lymphoma, and in lungs this condition should be thought of, especially when the images reveal pulmonary nodularity, lymphocytic interstitial pneumonia and lymphadenopathy. Although, pulmonary artery hypertension was traditionally and exceptionally linked with Sjogren's syndrome, together with systemic lupus erythematosus, they are now acknowledged to be the most common pulmonary vascular disease in east Asian populations, even over patients with systemic sclerosis. Although there are no controlled prospective trials to treat pulmonary disease in Sjogren's syndrome, the mainstay treatment modality still falls on glucocorticoid therapy (systemic and inhaled), combined with immune modulators or alone. Most of the evidence sustains successful outcomes based on reported cases or case series.

Pulmonary manifestations of connective tissue diseases (CTD) carry high morbidity and potential mortality, and the most serious pulmonary type is interstitial lung disease (ILD). Identifying and promptly intervening CTD-ILD with immune suppressor therapy will change the natural course of the disease resulting in survival improvement. Compared to idiopathic pulmonary fibrosis, the most common presentation of idiopathic interstitial pneumonia (IIP), CTD-ILD carries a better prognosis due to the response to immune suppressor therapy. Nonspecific interstitial pneumonia (NSIP) is the most common type of CTD-ILD that is different from the fibrotic classical presentation of IPF, known as usual interstitial pneumonia (UIP). An exception is rheumatoid arthritis that presents more frequently with UIP type. Occasionally, IPF may not have typical radiographic features of UIP, and a full assessment to differentiate IPF from CTD-ILD is necessary, including the intervention of a multidisciplinary team and the histopathology. Interstitial pneumonia with autoimmune features (IPAF) shows promising advantages to identify patients with ILD who have some features of a CTD without a defined autoimmune disease and who may benefit from immune suppressors. A composition of clinical, serological, and morphologic features in patients presenting with ILD will fulfill criteria for IPAF. In summary, the early recognition and treatment of CTD-ILD, differentiation from IPF-UIP, and identification of patients with IPAF fulfill the assessment by the clinician for an optimal care.

Sjogren's syndrome is an autoimmune connective tissue disease targeting the exocrine glands and frequently affecting the respiratory system. The pulmonary disease is the most important extra-glandular manifestation as it carries most of the morbidity and mortality. Typically, it affects the small airways ranging from mild to severe respiratory symptoms. The upper airways are also commonly involved, predisposing sinusitis to occur more frequently than in the normal population. Lymphocytic interstitial pneumonia was initially thought to be the prevailing parenchymal disease; however, multiple cohorts report non-interstitial pneumonia to be the most frequent subtype of interstitial lung disease. In the review of high-resolution computed tomography scans, cystic lesions are commonly found and associate with both the small airways and parenchymal disease. Under their presence, amyloidosis or lymphomas should be considered in the differential. Overall, Sjogren's syndrome has a higher risk for lymphoma, and in lungs this condition should be thought of, especially when the images reveal pulmonary nodularity, lymphocytic interstitial pneumonia and lymphadenopathy. Although, pulmonary artery hypertension was traditionally and exceptionally linked with Sjogren's syndrome, together with systemic lupus erythematosus, they are now acknowledged to be the most common pulmonary vascular disease in east Asian populations, even over patients with systemic sclerosis. Although there are no controlled prospective trials to treat pulmonary disease in Sjogren's syndrome, the mainstay treatment modality still falls on glucocorticoid therapy (systemic and inhaled), combined with immune modulators or alone. Most of the evidence sustains successful outcomes based on reported cases or case series.

Rationale Two antifibrotic medications, nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the US. Few data have been published on the use of these medications in clinical practice. Objective To investigate patterns of use of antifibrotic medications in the US. Methods The IPF-PRO Registry, a multicenter US registry, has enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Data from patients enrolled from 5 June 2014 to 4 March 2018 were used to determine antifibrotic medication use ("treatment") in the enrollment window and a follow-up window approximately 6 months later. Associations between patient characteristics and treatment status were tested using logistic regression. Results Overall, 551 of 782 eligible patients (70.5%) were treated in the enrollment window. Younger age, lower FVC % predicted, oxygen use with activity, worse self-rated health based on the Short Form-12 (SF-12) or St George's Respiratory Questionnaire score, referral to the enrolling center by a pulmonologist, use of lung biopsy in diagnosis, and carrying a diagnosis of IPF to the enrolling center were associated with being treated. Among 534 patients treated at enrollment who had follow-up data, 94.0% remained treated in follow-up. Better self-rated health based on the SF-12 mental component score or EuroQoL score, and not using oxygen with activity at enrollment, were associated with continuing treatment in follow-up. Among 172 patients who were untreated at enrollment and had follow-up data, 29.7% started treatment in follow-up. Lower DLco % predicted, a family history of ILD, a history of sleep apnea, and a definite diagnosis of IPF at enrollment were associated with starting treatment in follow-up. Conclusions The majority of patients in the IPF-PRO Registry were receiving an approved medication for IPF at enrollment. Treatment at enrollment was associated with greater disease severity, more compromised quality of life and the use of oxygen with activity. Clinical trial registered with ClinicalTrials.gov (NCT01915511).

Dermatomyositis (DM) is an idiopathic inflammatory disorder that presents with proximal muscle weakness and typical DM skin changes. DM can involve other organs such as the lung, esophagus, and heart. Diaphragmatic muscle paralysis is an unrecognized clinical presentation of acute DM exacerbation. A 58-year-old man with a history of DM presented to the hospital after sustaining a cardiorespiratory arrest. Before arrest, he had been suffering from progressive dyspnea and muscle weakness. Immunosuppressive therapy of tacrolimus for DM was recently discontinued due to renal toxicity. Bedside ultrasound of the diaphragm while intubated revealed evidence of bilateral diaphragmatic paralysis. After extubation, supine and upright pulmonary function tests (PFT) and sniff test results strengthened the diagnosis of diaphragmatic paralysis. The patient was worked up for an acute DM exacerbation as the likely etiology of the severe diaphragmatic muscle weakness (diaphragmatic paralysis) and ventilatory failure. Skin and muscle biopsy confirmed the diagnosis of active DM. The patient was treated with high dose steroids and mycophenolate mofetil, following which he soon recovered.

BackgroundMatrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.MethodsThe IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.ResultsAll the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.ConclusionsCirculating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.

This case demonstrates chronic fibrosing pleuritis, as a rare pulmonary aetiology for mortality in patients with Degos disease or malignant atrophic papulosis (MAP). Knowledge of this unusual complication will help physicians identify this entity early and provide appropriate treatment.Patients with MAP die from gastrointestinal and brain involvement within 2–3 years of diagnosis. This case is unique as the patient survived for 9 years and died secondary to respiratory failure, which had not been reported before. Our patient was a young man, diagnosed with MAP at the age of 17. His skin and gastrointestinal disease were controlled with eculizumab and parenteral treprostinil. The patient developed severe restrictive pulmonary disease, required ventilatory support, and died from respiratory failure. An autopsy revealed chronic fibrosis pleuritis. Longer surviving patients with MAP might suffer from significant respiratory disease. Pulmonary function test should be obtained to identify subclinical respiratory limitation.

The sarcoidosis patient who seeks surgical management for obesity presents many challenges. The interaction between sarcoidosis and obesity complicates both disorders and creates special issues to consider when contemplating surgery. This manuscript will review the approach to pre- and postoperative management of the sarcoidosis patient undergoing bariatric surgery.

Acute water intoxication (AWI) is a disorder of excess water intake that can manifest in neurological injury and death. We describe a case of a 54-year-old man that presents to the emergency department with a generalized toxic-clonic seizure due to AWI. Initial computed tomography of the brain demonstrated diffuse cerebral edema. However, with correction of serum sodium over the one hospital day, the patient's neurological symptoms and imaging completely resolved. Clinicians should recognize of reversibility of this entity with management of hyponatremia.

Patients with pulmonary arterial hypertension (PAH) usually die from progressive right ventricular failure. Mechanical complications due to pulmonary artery (PA) enlargement are rare and include tracheobronchial and left main coronary artery compression, and PA dissection. A 62-year-old female with PAH was seen in our office for follow-up. During the evaluation, spirometry was performed, which revealed a severe obstructive ventilatory limitation. Subsequent workup identified compression of bilateral mainstem bronchi from the dilated PA as the aetiology for the abnormal spirometry. Very few cases of this rare complication have been reported in the literature. A significant dilation of the PA is necessary (>4 cm) for the occurrence of these complications. Dilation of PA is an independent risk factor for sudden unexpected death in patients with PAH.

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia with thrombocytopenia. In addition to the primary TMA syndromes, microangiopathic hemolytic anemia with thrombocytopenia can be seen in many systemic diseases. Transplant associated TMA (TA-TMA) affects patients following stem cell or solid organ transplant. A 48-year-old male who underwent autologous stem cell transplant for nonsecretory multiple myeloma was admitted to our hospital with worsening anemia, thrombocytopenia, renal dysfunction and hepatosplenomegaly. Initial blood work revealed rare schistocytes and normal lactate dehydrogenase and haptoglobin levels. He underwent an extensive workup looking for an infectious, inflammatory or malignant etiology but a definitive diagnosis could not be reached. Over his prolonged stay at the hospital, he suffered from multiorgan failure and eventually passed away. An autopsy revealed TMA involving all clinically affected organ systems and was deemed to be the cause of his demise. The absence of typical blood work suggestive of hemolysis does not rule out a diagnosis of TA-TMA. Knowledge of this rare disease entity will help physicians identify and treat this life-threatening condition early and effectively.

Neurosarcoidosis (NS) is a rare disease, affecting only 3%–10% of patients with sarcoidosis. The clinical presentation can be protean and often represents a diagnostic challenge. Cerebrospinal fluid (CSF) ACE level has poor sensitivity, but high specificity for establishing a diagnosis of NS. We present a case of NS in a middle-aged African American woman who presented with dysphagia and dysphonia. An extensive radiological workup was negative for structural brain disease. CSF studies demonstrated lymphocyte predominant pleocytosis with an elevated ACE level. A diagnosis of possible neurosarcoidosis was made. She responded to systemic steroid therapy with complete resolution of her symptoms over the next five months. In the appropriate clinical setting, an elevated CSF ACE level could be of paramount importance for making a diagnosis of NS.

A 65-year-old man was brought to the emergency department with right upper quadrant (RUQ) abdominal pain for 4 hours. His medical history included colon cancer for which he underwent right hemicolectomy in May 2019. A preoperative CT of the abdomen showed gallstones; however, a cholecystectomy was

A 57-year-old woman with bullous emphysema and very severe airflow limitation with a forced expiratory volume in the first second of 18% predicted, presented to an outside facility with worsening cough, sputum production and shortness of breath. She had been hospitalised multiple times in the last 6

Case Presentation A 14-year-old girl initially presented to a pediatric gastroenterology office with a 1-month history of right upper quadrant abdominal pain, which radiated to the right shoulder and back. Her pain was worse after heavy meals and with deep breaths. She reported anorexia, fatigue, dyspnea while playing soccer, and a 5-pound weight loss. She denied any fevers, cough, or changes in her bowel habits.