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Clinical Characteristics, Hospital outcome and Prognostic Factors of Patients with Ventilator-related Pneumothorax.

Mechanical ventilation is a common cause of iatrogenic pneumothorax in intensive care units (ICU). Most of the patients with ventilator-related pneumothorax (VRP) have underlying lung diseases and is associated with increased morbidity and mortality. The prognostic factors of VRP are not clear. The objective of this study was to find the possible prognostic factors.

Methods: Analysis of retrospectively collected data of patients with pneumothorax induced by mechanical ventilation. Data were obtained concerning demographics, acute physiology and chronic health evaluation (APACHE) II score, organ failure, underlying diseases, interval between the start of mechanical ventilation and pneumothorax, arterial blood gas, respiratory parameters and patient outcomes.

Results: One hundred and twenty-four patients with VRP were included for analysis. The incidence rate of VRP was 0.4% (124/31660), and the mortality rate was 77.4%. The patients with VRP had higher hospital mortality rate than that of mechanically ventilated patients without pneumothorax (77.4% vs. 13.7%, P < 0.001) or patient with procedure-related pneumothorax (77.4% vs. 29.4%, P < 0.001). Most cases of VRP occurred in the early phase of mechanical ventilation, and 8.9% of the patients had a later episode of pneumothorax on the opposite lung. The interval between two episodes of VRP was short, at a median time of 2 days. Cox regression analysis showed that tension pneumothorax (P = 0.001), PaO2/FiO2 < 200 (P = 0.002), and APACHE II score (P = 0.008) were significantly associated with death.

Conclusions: VRP patients with tension pneumothorax or PaO2/FiO2 < 200 had a higher risk of death. APACHE II scores were associated with mortality in the VRP patients with PaO2/FiO2 ≥ 200 mmHg.

Pathology in Drug Discovery and Development.

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The rapid pace of drug discovery and drug development in oncology, immunology and ophthalmology brings new challenges; the efficient and effective development of new targeted drugs will require more detailed molecular classifications of histologically homogeneous diseases that show heterogeneous clinical outcomes.

To this end single companion diagnostics for specific drugs will be replaced by multiplex diagnostics for entire therapeutic areas, preserving tissue and enabling rapid molecular taxonomy. The field will move away from the development of new molecular entities as single agents, to which resistance is common. Instead a detailed understanding of the pathological mechanisms of resistance, in patients and in preclinical models, will be key to the validation of scientifically rational and clinically effective drug combinations. To remain at the heart of disease diagnosis and appropriate management, pathologists must evolve into translational biologists and biomarker scientists. Herein, we provide examples of where this metamorphosis has already taken place, in lung cancer and melanoma, where the transformation has yet to begin, in the use of immunotherapies for ophthalmology and oncology, and where there is fertile soil for a revolution in treatment, in efforts to classify glioblastoma and personalize treatment. The challenges of disease heterogeneity, the regulatory environment and adequate tissue are ever present, but these too are being overcome in dedicated academic centers.

In summary, the tools necessary to overcome the "whens" and "ifs" of the molecular revolution are in the hands of pathologists today, it is a matter of standardization, training and leadership to bring these into routine practice and translate science into patient benefit. This Annual Review Issue of the Journal of Pathology highlights the central role for pathology in modern drug discovery and development.

New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare(R) cohort.

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Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. Classically, diagnosis is based on a triad including hemoptysis, diffuse parenchymal infiltrates on chest X-rays, and iron-deficiency anemia. We present the French pediatric cohort of IPH collected through the French Reference Center for Rare Lung Diseases (RespiRare(R), www.respirare.fr).

METHODS: Since 2008, a national network/web-linked RespiRare(R) database has been set up in 12 French pediatric respiratory centres. It is structured as a medical recording tool with extended disease-specific datasets containing clinical information relevant to all forms of rare lung diseases including IPH.

RESULTS: We identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0] yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16, 64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n = 11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung biopsy (6/25). In screened patients, initial auto-immune screening revealed positive ANCA (n = 6, 40%), ANA (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%). All the patients were initially treated by corticosteroids. In 13 cases, immunosuppressants were introduced due to corticoresistance and/or major side effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage.

CONCLUSION: The present cohort provides substantial information on clinical expression and outcomes of pediatric IPH. Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors.

Pulmonary rehabilitation underused in COPD

Data from an Australian hospital show that chronic obstructive pulmonary disease patients admitted for exacerbations are rarely referred for pulmonary rehabilitation, despite it being strongly recommended by national treatment guidelines.

Prednisolone or dexamethasone for acute exacerbations of asthma: do they have similar efficacy in the management of exacerbations of childhood asthma?

Scenario You are asked to see a 6-year-old child who has come into hospital with an acute exacerbation of asthma. She is able to talk in full sentences, however, her respirations are 40/min with audible wheeze, and you prescribe 10 puffs of salbutamol as initial management.

The British Thoracic Society (BTS) guidelines recommend early use of steroids to decrease admission rate and length of stay,1 and you feel steroids would be of value for this child. However the mother of your patient explains her daughter hates taking any medications. You have read an article about dexamethasone being a shorter treatment course with better compliance and wonder if it has similar efficacy to prednisolone. Question In children who have an acute exacerbation of asthma requiring steroids (population), does ...

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