Pulmonary, circulatory and renal considerations in the early postoperative management of the lung transplant recipient.

Lung transplantation volumes and survival rates continue to increase worldwide. Primary graft dysfunction (PGD) and acute kidney injury (AKI) are common early postoperative complications that significantly affect short-term mortality and long-term outcomes. These conditions share overlapping risk factors and are driven, in part, by circulatory derangements. The prevalence of severe PGD is up to 20% and is the leading cause of early death. Patients with pulmonary hypertension are at a higher risk. Prevention and management are based on principles learned from acute lung injury of other causes. Targeting the lowest effective cardiac filling pressure will reduce alveolar edema formation in the setting of increased pulmonary capillary permeability. AKI is reported in up to one-half of lung transplant recipients and is strongly associated with one-year mortality as well as long-term chronic kidney disease. Optimization of renal perfusion is critical to reduce the incidence and severity of AKI. In this review, we highlight key early post-transplant pulmonary, circulatory, and renal perturbations and our center's management approach.

Utilizing Clinical Pharmacy Specialists to Address Access to Care Barriers in the Veteran Population for the Management of Diabetes.

OBJECTIVE: To show that clinical pharmacy specialists (CPSs) can be utilized in remote facilities to provide appropriate diabetes outcomes along with potential cost savings. METHODS: A retrospective cohort chart review conducted at the Veterans Affairs North Texas Healthcare System (VANTHCS) evaluated outcomes in patients with type 2 diabetes mellitus referred to CPSs at Fort Worth Outpatient Clinic (FWOPC) or the endocrinologist-managed specialty clinic at the Dallas VA Medical Center (DVAMC). The primary outcome was percentage of patients reaching hemoglobin A1c (HbA1c) goal of <8%. Secondary outcomes were percentage of patients reaching HbA1c <7%, time to reach HbA1c goals of <8% and <7%, and cost savings. RESULTS: There was no statistically significant difference in the number of patients reaching HbA1c goal <8% in the FWOPC (65.3%) compared to the DVAMC (55.8%). Secondary end points comparing FWOPC and DVAMC found no difference in patients reaching HbA1c <7% (20.8% vs 19.2%) and time to reach HbA1c goal of <8% (4.5 vs 6 months) and <7% (8.5 vs 7.5 months). Cost-saving analysis demonstrated a composite of US$350 292 could be saved by the VANTHCS facility if patients continued to be referred to CPS. CONCLUSION: CPSs can be utilized in diabetes management to provide similar health outcomes as the endocrinologist-managed clinic and to potentially allow for facility cost savings.

Idiopathic non-specific interstitial pneumonia.

Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that may be idiopathic or secondary to connective tissue disease, toxins or numerous other causes. Idiopathic NSIP is a rare diagnosis and requires exclusion of these other possible causes. Patients typically present in mid-adulthood with dyspnoea, cough and often constitutional symptoms including fever and fatigue. The disease has a female predominance, and more than 50% of patients have never smoked. Physical exam features mild hypoxaemia and inspiratory rales. Pulmonary function tests demonstrate restriction and a low diffusing capacity for carbon monoxide. High-resolution computed tomography abnormalities include predominantly lower lobe subpleural reticular changes, traction bronchiectasis and ground-glass opacities; honeycombing is rarely seen. An evaluation of the underlying pathology is necessary for a firm diagnosis. Histologically, alveolar and interstitial mononuclear cell inflammation and fibrosis are seen in a temporally uniform pattern with preserved underlying alveolar architecture. NSIP must be differentiated from other parenchymal lung diseases including idiopathic pulmonary fibrosis and hypersensitivity pneumonitis. A thorough exposure history and assessment for underlying connective tissue diseases are highly important, as positive findings in these categories would likely denote a case of secondary NSIP. A multi-disciplinary discussion that includes pulmonologist(s), radiologist(s) and pathologist(s) assists in reaching a consensus diagnosis and improves diagnostic accuracy. Treatment of idiopathic NSIP, although not well proven, is generally instituted in the form of immunosuppression. Prognosis is favourable compared with idiopathic pulmonary fibrosis, although the diagnosis still carries an attributable mortality. Herein we will summarize the clinical characteristics and management of idiopathic NSIP.

Critically Ill Patients with Interstitial Lung Disease.

Interstitial lung disease (ILD) is a clinical syndrome of various etiologies and histopathologic categorization that, when clinically significant, impair respiratory function. Patients with ILD may develop critical illness from respiratory failure, nonpulmonary organ failure, or after surgical procedures. Additionally, the intensivist must be adept at recognizing exacerbation syndromes, which can complicate the disease course of some forms of ILD. This article discusses mechanical ventilation, noninvasive mechanical ventilation, exacerbation syndromes, and surgical concerns for patients with ILD who are critically ill.

Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation.

RATIONALE: Extracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a living organ. In the lung, fibroblasts exist in ECM-rich interstitial spaces and are key effectors of lung fibrogenesis. OBJECTIVES: To better address how ECM influences fibroblast phenotype in a disease-specific manner, we developed a culture system using acellular human normal and fibrotic lungs. METHODS: Decellularization was achieved using treatment with detergents, salts, and DNase. The resultant matrices can be sectioned as uniform slices within which cells were cultured. MEASUREMENTS AND MAIN RESULTS: We report that the decellularization process effectively removes cellular and nuclear material while retaining native dimensionality and stiffness of lung tissue. We demonstrate that lung fibroblasts reseeded into acellular lung matrices can be subsequently assayed using conventional protocols; in this manner we show that fibrotic matrices clearly promote transforming growth factor-ß-independent myofibroblast differentiation compared with normal matrices. Furthermore, comprehensive analysis of acellular matrix ECM details significant compositional differences between normal and fibrotic lungs, paving the way for further study of novel hypotheses. CONCLUSIONS: This methodology is expected to allow investigation of important ECM-based hypotheses in human tissues and permits future scientific exploration in an organ- and disease-specific manner.