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Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

Background: Invasive candidiasis is not uncommon in critically ill patients but has variable epidemiology and outcomes between intensive care units (ICUs). This study evaluated the epidemiology, characteristics, management, and outcomes of patients with invasive candidiasis at 6 ICUs of 2 tertiary care centers. Methods: This was a prospective observational study of all adults admitted to 6 ICUs in 2 different hospitals between August 2012 and May 2016 and diagnosed to have invasive candidiasis by 2 intensivists according to predefined criteria. The epidemiology of isolated Candida and the characteristics, management, and outcomes of affected patients were studied. Multivariable logistic regression analyses were performed to identify the predictors of non-albicans versus albicans infection and hospital mortality. Results: Invasive candidiasis was diagnosed in 162 (age 58.4 ± 18.9 years, 52.2% males, 82.1% medical admissions, and admission Acute Physiology and Chronic Health Evaluation II score 24.1 ± 8.4) patients at a rate of 2.6 cases per 100 ICU admissions. On the diagnosis day, the Candida score was 2.4 ± 0.9 in invasive candidiasis compared with 1.6 ± 0.9 in Candida colonization ( P < .01). The most frequent species were albicans (38.3%), tropicalis (16.7%), glabrata (16%), and parapsilosis (13.6%). In patients with candidemia, antifungal therapy was started on average 1 hour before knowing the culture result (59.6% of therapy initiated after). Resistance to fluconazole, caspofungin, and amphotericin B occurred in 27.9%, 2.9%, and 3.1%, respectively. The hospital mortality was 58.6% with no difference between albicans and non-albicans infections (61.3% and 54.9%, respectively; P = .44). The independent predictors of mortality were renal replacement therapy after invasive candidiasis diagnosis (odds ratio: 5.42; 95% confidence interval: 2.16-13.56) and invasive candidiasis leading/contributing to ICU admission versus occurring during critical illness (odds ratio: 2.87; 95% confidence interval: 1.22-6.74). Conclusions: In critically ill patients with invasive candidiasis, non-albicans was responsible for most cases, and mortality was high (58.6%). Antifungal therapy was initiated after culture results in 60% suggesting low preclinical suspicion. Study registration: NCT01490684; registered in ClinicalTrials.gov on February 11, 2012.

Introduction: This study was conducted in response to the rising incidence of drug resistance observed in the intensive care unit (ICU) of King Fahad Medical City. Methodology: A retrospective observational study was conducted in the ICU of King Fahad Medical City between October 2003 and April 2012. Data were collected using a structured data sheet. Results: Nine episodes of infection with colistin-resistant Enterobacteriacae were recorded in seven patients. Five were females with an average age of 59.75 years. All patients had multiple co-morbidities; five had diabetes mellitus. In five of the episodes, Klebsiella pneumoniae was responsible, Serratia marcescens was reported in two, while Enterobacter aerogenes and Providencia stuartii were responsible for one episode of infection each. Prior colistin use was documented in all but one patient. Colistin resistance was defined by a minimum inhibitory concentration (MIC) of > 4 µg/mL according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint for Enterobacteriacae. Various antibiotics were used to treat the patients, with mortality reported in two. Conclusion: Infection due to colistin-resistant Enterobacteriacae is a rising challenge in Saudi Arabia; colistin use is thought to be associated with these infections. This calls for a stricter antimicrobial stewardship program and improved infection control measures to curb the rising trend of antibiotic resistance.

A broad spectrum of pathologies that involve the laryngotracheobronchial airway and imaging plays a crucial role in evaluating these abnormalities. Computed tomography with virtual bronchoscopy has been found to be very helpful in defining the location, extent, and nature of these lesions, and is increasingly being used even in patients with contraindications for fiberoptic bronchoscopy and laryngoscopy. Ionizing radiation, associated with virtual bronchoscopy, can be minimized by using low-dose multidetector computed tomography and hybrid iterative reconstruction techniques. Furthermore, retrospectively generated virtual bronchoscopy from a routinely acquired computed tomography data set eliminates additional cost and radiation. In the future, virtual bronchoscopy assisted with advanced navigational techniques will broaden the diagnostic and therapeutic landscape. This article presents the characteristic features of common and rare laryngotracheobronchial pathologies seen with virtual bronchoscopy.