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Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

Rigid bronchoscopy is an invaluable tool for the management of airway disorders and an essential skill for an interventional pulmonologist. Since its introduction in the late 19th century, it has remained an important technique for the management of central airway obstruction, foreign body aspiration and massive hemoptysis. Areas covered: This article will review the history, indications, contraindication, technique and complications of rigid bronchoscopy. We will also briefly discuss the methods of anesthesia and ventilation and finally our perspective on the future of rigid bronchoscopy. Expert commentary: Although the rise of flexible bronchoscopy in the 1960s led to a decline in the use of rigid bronchoscopy, the last two decades have witnessed resurgence in its popularity. We anticipate that it will remain an important tool used by interventional pulmonologists for decades to come. We suggest that interventional pulmonologists must have training and develop expertise in this technique.

The reaction between aryl or heteroarylhydrazines with fluorinated β-diketones (CF3COCH2COR) yields a variety of 3-, 5-, and 3,5-trifluoromethylpyrazoles and 5-trifluoromethyl-5-hydroxy-Δ2-pyrazolines. Twenty-one of such compounds have been isolated and identified by 13C and 19F NMR. Together with the results from the literature they provide a comprehensive overview of the reaction. Semi-empirical calculations at the PM3 level have been used to rationalize these results. The outcome that emerges seems to be that the dehydration of a pair of 3,5-dihydroxypyrazolidines kinetically controls the isomer formed.Key words: hydrazines, 1,3-diketones, pyrazolines, pyrazoles, PM3 calculations.

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The severe acute respiratory syndrome (SARS)-CoV-2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. As such, surgeons will be called upon to perform tracheotomy for a subset of these chronically intubated patients. As seen during the SARS and the SARS-CoV-2 outbreaks, aerosol-generating procedures (AGP) have been associated with higher rates of infection of medical personnel and potential acceleration of viral dissemination throughout the medical center. Therefore, a thoughtful approach to tracheotomy (and other AGPs) is imperative and maintaining traditional management norms may be unsuitable or even potentially harmful. We sought to review the existing evidence informing best practices and then develop straightforward guidelines for tracheotomy during the SARS-CoV-2 pandemic. This communication is the product of those efforts and is based on national and international experience with the current SARS-CoV-2 pandemic and the SARS epidemic of 2002/2003. K E Y W O R D SCOVID, critical care, head and neck surgery, otolaryngology, tracheostomy

The pleural mesothelium, derived from the embryonic mesoderm, is formed by a metabolically active monolayer of cells that blanket the chest wall and lungs on the parietal and visceral surfaces, respectively. The pleura and lungs are formed as a result of an intricate relationship between the mesoderm and the endoderm during development. Mesenchymal signaling pathways such as Wnt/B-catenin, Bmp4, and sonic hedgehog appear to be quintessential for lung development. Pleural Mesothelial Cells (PMCs) are known to express Wilms tumor-1 (Wt1) gene and in lineage labeling studies of the developing embryo, PMCs were found to track into the lung parenchyma and undergo mesothelial-mesenchymal transition (MMT) to form α-smooth muscle actin (α-SMA)-positive cells of the mesenchyme and vasculature. There is definite evidence that mesothelial cells can differentiate and this seems to play an important role in pleural and parenchymal pathologies. Mesothelial cells can differentiate into adipocytes, chondrocytes, and osteoblasts; and have been shown to clonally generate fibroblasts and smooth muscle cells in murine models. This supports the possibility that they may also modulate lung injury-repair by re-activation of developmental programs in the adult reflecting an altered recapitulation of development, with implications for regenerative biology of the lung. In a mouse model of lung fibrosis using lineage-tracing studies, PMCs lost their polarity and cell-cell junctional complexes, migrated into lung parenchyma, and underwent phenotypic transition into myofibroblasts in response to the pro-fibrotic mediator, transforming growth factor-β1 (TGF-β1). However, intra-pleural heme-oxygenase-1 (HO-1) induction inhibited PMC migration after intra-tracheal fibrogenic injury. Intra-pleural fluorescein isothiocyanate labeled nanoparticles decorated with a surface antibody to mesothelin, a surface marker of mesothelial cells, migrate into the lung parenchyma with PMCs supporting a potential role for pleural based therapies to modulate pleural mesothelial activation and parenchymal disease progression.

A multikilogram-scale synthesis of l-lyxonolactone-2,3-O-isopropylidene is reported. It proceeds efficiently from an optimized, large-scale, aqueous bromine oxidation of d-ribose to d-ribonolactone including a one-pot isopropylidene formation, and subsequent conversion of the d-ribonolactone-2,3-O-isopropylidene to l-lyxonolactone-2,3-O-isopropylidene via the derived C5-mesylate and intramolecular relactonization of the product of aqueous potassium hydroxide cleavage of the d-ribonolactone ring. The inversion of configuration at the C4-chiral center is understood in terms of an intermediating C4−C5-epoxide. The overall process is noteworthy for its operational simplicity, stereochemical integrity, and use of inexpensive chemicals.