A Systemic Review on the Diagnostic Accuracy of Point-of-Care Ultrasound in Patients With Undifferentiated Shock in the Emergency Department.

Early identification of the shock type and correct diagnosis is associated with better outcomes. Previous studies have suggested that point-of-care ultrasound (POCUS) increases the diagnostic accuracy of patients in undifferentiated shock. However, a complete overview of the diagnostic accuracy of POCUS and the related treatment changes when compared to standard care is still limited. Our objective was to compare POCUS against standard practice regarding the diagnostic accuracy and specific therapeutic management changes (fluid volume administration and vasopressor use) in patients with undifferentiated shock in the emergency department (ED). We conducted a systematic review in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic search was performed using Embase, PubMed, Cochrane Central Register for Controlled Trials, and clinicaltrials.gov. Two physicians independently selected the articles and assessed the quality of the studies independently with the Quadas-2 tool. All included studies used POCUS in adult patients in undifferentiated shock and described diagnostic accuracy or specific therapeutic management changes (fluid volume administration or vasopressor use) and compared this to standard care. The primary outcome was diagnostic accuracy. Secondary outcomes were the amount of fluid administered and vasopressor use in the ED. Only articles published after 1996 were included. There were 10,805 articles found of which 6 articles were included. Four out of six studies reported diagnostic accuracy, three reported on fluid administration and vasopressors. We found that the diagnostic accuracy improved through the use of POCUS when compared to the standard care group, increasing overall diagnostic accuracy from 45-60% to 80-89% when combined with clinical information. There was no significant difference in fluid administration or vasopressor use between the groups. In our systematic review, we found that the use of POCUS in patients that presented with undifferentiated shock in the ED improved the diagnostic accuracy of the shock type and final diagnosis. POCUS resulted in no changes in fluid administration or vasopressor use when compared to standard care. However, the results should be interpreted within the limitations of some of the studies that were included in the review.

Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review.

UNLABELLED: Idiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much enthusiasm for the treatment of several conditions, including lung diseases. Human trials of mesenchymal stromal cell (MSC) therapy for pulmonary fibrosis are under way. To shed light on the potential usefulness of MSCs for human disease, we aimed to systematically review the preclinical literature to determine if MSCs are beneficial in animal bleomycin pulmonary fibrosis models. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal bleomycin models of pulmonary fibrosis. Studies using embryonic stem cells or induced pluripotent stem cells were excluded. Seventeen studies were selected, all of which used MSCs in rodents. MSC therapy led to an improvement in bleomycin-induced lung collagen deposition in animal lungs and in the pulmonary fibrosis Ashcroft score in most studies. MSC therapy improved histopathology in almost all studies in which it was evaluated qualitatively. Furthermore, MSC therapy was found to improve 14-day survival in animals with bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage total and neutrophil counts, as well as transforming growth factor-ß levels, were also reduced by MSCs. MSCs are beneficial in rodent bleomycin pulmonary fibrosis models. Since most studies examined the initial inflammatory phase rather than the chronic fibrotic phase, preclinical data offer better support for human trials of MSCs in acute exacerbations of pulmonary fibrosis rather than the chronic phase of the disease. SIGNIFICANCE: There has been increased interest in mesenchymal stromal cell therapy for lung diseases. A few small clinical trials are under way in idiopathic pulmonary fibrosis. Preclinical evidence was assessed in a systematic review, as is often done for clinical studies. The existing studies offer better support for efficacy in the initial inflammatory phase rather than the fibrotic phase that human trials are targeting.

Effect of infection with transmissible strains of Pseudomonas aeruginosa on lung transplantation outcomes in patients with cystic fibrosis.

BACKGROUND: Compared with patients infected with unique strains of Pseudomonas aeruginosa, patients with cystic fibrosis who are infected with transmissible strains of P aeruginosa, such as the Liverpool epidemic strain, have a 3-fold greater risk of death or lung transplant. We aimed to determine if pre-operative infection with transmissible strains of P aeruginosa was similarly associated with poor health outcomes after lung transplant. METHODS: We had prospectively identified and characterized endobronchial infections in 446 adult cystic fibrosis patients in Ontario, Canada, from September 2005 until December 2009. P aeruginosa isolated from sputum taken at 3-month intervals was genotyped, and patients were characterized as being infected with 1 of 2 transmissible strains or, alternatively, with unique strains of P aeruginosa. We monitored patients until 2013 and collected data on patients from the cohort who subsequently received a lung transplant. The primary outcome was survival after transplantation. RESULTS: We identified 56 lung transplant recipients from the cohort of 446 patients, including 18 infected with transmissible strains of P aeruginosa and 26 infected with unique P aeruginosa strains. Post-transplant survival at 3 years was 86% in the transmissible group and 84% in the unique group (p = 0.65). No significant differences between groups were found regarding bronchiolitis obliterans-free survival, the frequency of acute rejection episodes, the frequency of post-transplant respiratory tract infection, or the rate of change of post-transplant forced expiratory volume in 1 second. CONCLUSIONS: Pre-operative infection with transmissible strains of P aeruginosa is not associated with poorer post-transplant outcomes compared with patients infected with unique strains of P aeruginosa.

Indwelling pleural catheters for pleural effusions associated with end-stage renal disease: a case series.

BACKGROUND: Pleural effusions are a common complication of end-stage renal disease.These effusions are occasionally refractory to medical management, but few options are then available. Indwelling pleural catheter insertion (IPC) has been well described for the management of malignant pleural effusions and, more recently, of nonmalignant effusions of other origin. We aimed to analyze our experience and to evaluate the safety and feasibility of using IPCs for pleural effusion associated with end-stage renal disease. METHODS: We constructed a cohort of patients who underwent IPC insertion for pleural effusions associated with end-stage renal disease. The IPCs were inserted as a palliative measure in patients who had thoracentesis twice within the preceding 2 weeks, no evidence of infection and either failure to respond, complications or intolerance to maximal medical therapy, or if IPC insertion would enable discharge when the patient was hospitalized mainly for dyspnea due to pleural effusion. RESULTS: There were nine IPCs inserted in eight patients. Patients had significant dyspnea at baseline with a median baseline dyspnea index of 1.5 [interquartile range (IQR) 0­3]. Dyspnea improved significantly 2 weeks after catheter insertion with a median transitional dyspnea index of 6 (IQR 4.5­7.0). There was no occurrence of empyema or other major complications.Serum albumin did not decrease after catheter insertion. IPCs were removed in four patients(50%) and successful spontaneous pleurodesis occurred in three patients (37.5%) after a median of 77 days (IQR 9­208). CONCLUSION: IPC insertion for pleural effusions associated with end-stage renal disease appears safe and effective. Larger studies are needed, particularly regarding the impact of this intervention on quality of life.

Stem cells in animal asthma models: a systematic review.

BACKGROUND AIMS: Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting ß-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. METHODS: The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. RESULTS: Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. CONCLUSIONS: Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials.

Use of indwelling pleural catheters for cardiogenic pleural effusions.

BACKGROUND: Cardiogenic pleural effusions are rarely refractory to treatment of the underlying disease. Few options are available in these cases. Indwelling pleural catheter (IPC) insertion has been well described for the management of malignant pleural effusions. We present our experience with using IPCs for cardiogenic pleural effusion management. METHODS: We prospectively constructed a cohort of patients who underwent IPC insertion for cardiogenic pleural effusions. Patients were carefully selected, and the IPCs were inserted as a palliative measure or while awaiting cardiac transplantation. RESULTS: There were 43 IPCs inserted in 38 patients. Patients had significant dyspnea, with a mean baseline dyspnea index of 2.24 (95% CI, 1.53-2.94). There was significant improvement in dyspnea 2 weeks after IPC insertion, with a mean transitional dyspnea index of 6.19 (95% CI, 5.56-6.82). There was no occurrence of empyema. Pneumothorax, mostly ex vacuo, occurred in 11.6% of procedures but did not require further intervention. IPCs were removed in 18 patients (47.4%), and successful spontaneous pleurodesis occurred in 11 patients (29.0%) after a median of 66 days (interquartile range, 34-242 days). Patients who eventually had their catheters removed had better performance status (P = .008) and were less dyspneic (P = .005) at baseline and had longer survival (P < .0001). CONCLUSIONS: IPC insertion for cardiogenic pleural effusion is a feasible option in carefully selected patients. Further research is needed to confirm the results and to assess the impact of IPC insertion on the quality of life of these patients.

Management of malignant pleural effusions with indwelling pleural catheters or talc pleurodesis.

BACKGROUND: Management of malignant pleural effusion typically involves insertion of an indwelling pleural catheter (IPC) or chemical pleurodesis with agents such as talc. OBJECTIVES: To compare these management strategies with regard to success of pleural effusion management. METHODS: A retrospective cohort study was designed comparing patients with malignant and paramalignant pleural effusions and Eastern Cooperative Oncology Group performance status <4 managed with IPC insertion or talc pleurodesis (TP) through tube thoracostomy during noncontemporary three-year periods at a single centre. RESULTS: The IPC and TP groups comprised 193 and 167 patients, respectively. The pleural effusion control rate at six months was higher in the IPC group (52.7% versus 34.4% in the TP group; P<0.01), but the rate of freedom from catheter at 90 days and pleural effusion at 180 days was not significantly different (IPC 25.8% versus TP 34.4% [P=0.17]). Median effusion-free survival from the date of catheter insertion was significantly longer in the IPC group (101 days versus 58 days in the TP group; log-rank P=0.025). Both procedures were safe. DISCUSSION: While the results suggest better pleural effusion control and longer effusion-free survival with IPC insertion compared with TP, the present study had several limitations. Other recent studies have not shown one strategy to be clearly superior to the other. CONCLUSION: Both IPC insertion and TP remain acceptable options for the management of malignant pleural effusions.

Lung volume recruitment in multiple sclerosis.

INTRODUCTION: Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC) and cough but the time course of this impairment is unknown. Peak cough flow (PCF) is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. OBJECTIVES: Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. METHODS: We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. RESULTS: There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9-190.3) and PCF (192 mL/s/y, 95% 72-311) over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001) and PCF (p = 0.042). CONCLUSION: Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis.

TACE/ADAM-17 maturation and activation of sheddase activity require proprotein convertase activity.

Proprotein convertases (PCs) have been proposed to play a role in tumor necrosis factor-alpha converting enzyme (TACE) processing/activation. Using the furin-deficient LoVo cells, as well as the furin-proficient synoviocytes and HT1080 cells expressing the furin inhibitor alpha(1)-PDX, we demonstrate that furin activity alone is not sufficient for effective maturation and activation of the TACE enzyme. Data from in vitro and in vivo cleavage assays indicate that PACE-4, PC5/PC6, PC1 and PC2 can directly cleave the TACE protein and/or peptide. PC inhibition in macrophages reduced the release of soluble TNF-alpha from transmembrane pro-TNF-alpha. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation.