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Acute lung injury (ALI) affects over 10% of patients hospitalised in critical care, with acute respiratory distress syndrome (ARDS) being the most severe form of ALI and having a mortality rate in the region of 40%. There has been slow but incremental progress in identification of biomarkers that contribute to the pathophysiology of ARDS, have utility in diagnosis and monitoring, and that are potential therapeutic targets (Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Thompson T, Ware LB, Matthay MA, Lancet Respir Med 2014, 2:611–-620). However, a major issue is that ARDS is such a heterogeneous, multi-factorial, end-stage condition that the strategies for “lumping and splitting” are critical (Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX, Am J Respir Crit Care Med 2016, 194:147–-155). Nevertheless, sequencing of the human genome, the availability of improved methods for analysis of transcription to mRNA (gene expression), and development of sensitive immunoassays has allowed the application of network biology to ARDS, with these biomarkers offering potential for personalised or precision medicine (Sweeney TE, Khatri P, Toward precision medicine Crit Care Med; 2017 45:934-939).Biomarker panels have potential applications in molecular phenotyping for identifying patients at risk of developing ARDS, diagnosis of ARDS, risk stratification and monitoring. Two subphenotypes of ARDS have been identified on the basis of blood biomarkers: hypo-inflammatory and hyper-inflammatory. The hyper-inflammatory subphenotype is associated with shock, metabolic acidosis and worst clinical outcomes. Biomarkers of particular interest have included interleukins (IL-6 and IL-8), interferon gamma (IFN-γ), surfactant proteins (SPD and SPB), von Willebrand factor antigen, angiopoietin 1/2 and plasminogen activator inhibitor-1 (PAI-1). In terms of gene expression (mRNA) in blood there have been found to be increases in neutrophil-related genes in sepsis-induced and influenza-induced ARDS, but whole blood expression does not give a robust diagnostic test for ARDS.Despite improvements in management of ARDS on the critical care unit, this complex disease continues to be a major life-threatening event. Clinical trials of β2-agonists, statins, surfactants and keratinocyte growth factor (KGF) have been disappointing. In addition, monoclonal antibodies (anti-TNF) and TNFR fusion protein have also been unconvincing. However, there have been major advances in methods of mechanical ventilation, a neuromuscular blocker (cisatracurium besilate) has shown some benefit, and stem cell therapy is being developed. In the future, by understanding the role of biomarkers in the pathophysiology of ARDS and lung injury, it is hoped that this will provide rational therapeutic targets and ultimately improve clinical care (Seymour CW, Gomez H, Chang CH, Clermont G, Kellum JA, Kennedy J, Yende S, Angus DC, Crit Care 2017, 21:257).

A c c e p t e d m a n u s c r i p t AbstractThe aim of this pilot study was to explore the relative efficacy in terms of improvement in symptoms and lung function of combining fluticasone propionate/salmeterol combination (FSC) and tiotropium in patients with severe-to-very severe stable COPD. Ninety patients were randomized to receive 3 months of treatment in one of three treatment groups: (1) FSC 500/50 µg Diskus, 1 inhalation twice daily + placebo Handihaler 1 inhalation once-daily daily; (2) tiotropium 18 µg Handihaler, 1 inhalation once daily + placebo Diskus, 1 inhalation twice daily; (3) FSC 500/50 µg Diskus, 1 inhalation twice daily + tiotropium 18 µg Handihaler, 1 inhalation once-daily daily. Patients attended the clinic before and after 1 month, 2 months, and 3 months of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using a visual analog scale (VAS). Also the supplemental salbutamol use was measured. Eighty-one patients completed the 3-month treatment period: 26 patients receiving FSC, 26 patients receiving tiotropium, and 29 patients receiving FSC + tiotropium. Patients were withdrawn for COPD exacerbation. Improvements in trough FEV 1 with all treatments medications were observed by the first month when trough FEV 1 had improved significantly above baseline by 74 mL (p < 0.05) in the tiotropium group, by 117 mL (p < 0.05) in the FSC group and by 115 mL (p < 0.05) in FSC + tiotropium group. At the end of the study, trough FEV1 had improved significantly above baseline by141 mL (p < 0.05) in the tiotropium group, by 140 mL (p < 0.05) in the FSC group and by 186 mL (p < 0.05) in FSC + tiotropium group. The difference between FSC and tiotropium appeared to decrease, that between FSC and FSC + tiotropium appeared to increase and that between tiotropium and FSC + tiotropium remained almost similar with study duration. Our results suggest that adding FSC and tiotropium may provide benefits in symptomatic patients with severe-to-very severe stable COPD.

Spontaneous pneumomediastinum (SPM) is defined as the presence of air in the mediastinum, developing in the absence of traumatic, iatrogenic, or preceding pulmonary pathologies (emphysema, chronic bronchitis, and lung cancer). The aim of this study was to review our experiences with SPM, underlining its symptomatology, diagnosis, treatment, and followup, and defining a reasonable course of assessment and management. A retrospective case series was conducted to identify adult patients with SPM who were diagnosed and treated in our institution between 1998 and 2005. Eighteen patients (10 males) were identified (average age = 25 +/- 4.8 years). Acute onset of chest pain was the predominant symptom at presentation. All patients developed clinically evident subcutaneous emphysema and underwent chest computerized tomography. Fiber bronchoscopy and echocardiogram were used selectively (8 patients). The average hospital stay was 6 (+/-1.4) days. Sixteen patients were conservatively treated, and only two patients were treated with thoracic drainage due to a related pneumothorax. The disease followed a benign evolution in all patients and, as of today, no relapse has been reported. SPM is an uncommon pathology with a usually benign course. The authors discuss SPM. A diagnostic algorithmic approach is necessary to rule out severe secondary entities and consequences that need urgent treatment.

Surgery can offer seizure-free outcome for approximately one half of carefully selected patients with intractable focal epilepsy due to MCD. Complete resection of the MRI-apparent lesion may improve the likelihood for favorable outcome. MRI evidence of hemimegalencephaly or bilateral MCD suggests a low likelihood for postoperative freedom from seizures.

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