In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.
In the setting of marker-negative elevated LFT, the most likely histological diagnosis is fatty metamorphosis of the liver with occasional associated fibrosis.
Lung transplantation is the only viable option for many patients with chronic, end-stage lung diseases. However, 60% of patients within 5 years of transplant develop bronchiolitis obliterans syndrome (BOS) (1-4), a disease syndrome defined as a fall in FEV 1 of greater than 20% from baseline determined by the average of two measurements made at least 3 weeks apart (5). Median survival after onset of BOS is 3 to 4 years, with a range of 0 to 9.4 years (6-8). These survival numbers are comparable to other chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF). Similarly, although development of BOS is associated with progressive worsening of lung function, the rate of decline in FEV 1 after onset of BOS is believed to be variable among patients and over time (9). Although significant effort has been
What This Study Adds to the FieldRapid onset of BOS, female gender, pretransplant diagnosis of idiopathic pulmonary fibrosis, and single-lung transplantation are associated with worse pulmonary function after BOS onset.made to understand factors associated with the risk of development of BOS, little information has been published regarding the course of FEV 1 after onset of BOS and the effect of various variables on it. This information is important for patient counseling and management, but is also crucial for designing diagnostic and therapeutic clinical trials in the field of BOS.The objectives of this study were to characterize the course of FEV 1 over time after development of BOS, to describe the natural history of spirometric dysfunction, and to determine the predictors that influence the rate of functional decline of FEV 1 in a large cohort of well-characterized lung transplant recipients.
The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.
Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.
Rationale: Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotent mesenchymal stromal cell population. However, the clinical relevance of this novel cellular component of BAL and its association with bronchiolitis obliterans syndrome (BOS), a disease marked by progressive airflow limitation secondary to fibrotic obliteration of the small airways, remains to be determined. Objectives: In this study we investigate the association of number of mesenchymal stromal cells in BAL with development of BOS in human lung transplant recipients. Methods: Mesenchymal colony-forming units (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung transplant recipients. Poisson generalized estimating equations were used to determine the predictors of BAL mesenchymal CFU count. Measurements and Main Results: Higher CFU counts were noted early post-transplantation; time from transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P 5 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated with a 2.11-fold higher CFU count (P 5 0.02). There were 2.62-and 2.70-fold higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis obliterans (P 5 0.05) and organizing pneumonia (0.0003), respectively. In BAL samples obtained from BOS-free patients greater than 6 months post-transplantation (n 5 173), higher mesenchymal CFU counts (>10) significantly predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P , 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P , 0.0001) Cox regression analysis. Conclusions: Measurement of mesenchymal CFUs in the BAL provides predictive information regarding future BOS onset.
Current trends in the epidemiology, outcome and variables influencing mortality in bacteremic lung transplant recipients have not been fully described. We prospectively studied bacteremias in lung transplant recipients in a multicenter study between 2000-2004. Bacteremia was documented in 56 lung transplant recipients, an average of 172 days after transplantation. Multiple antibiotic resistance was documented in 48% of the isolates; these included 57% of the Gramnegative and 38% of the Gram-positive bacteria. Pulmonary infection was the most common source of resistant gram-negative bacteremias. Mortality rate at 28 days after the onset of bacteremia was 25% (14/56). Mechanical ventilation and abnormal mental status correlated independently with higher mortality (p < 0.05 for both variables). Bacteremia remains a significant complication in lung transplant recipients and is associated with considerable mortality. Recognition of variables portending a high risk for antibiotic resistance and for poor outcome has implications relevant for optimizing antibiotic prescription and for improving outcomes in lung transplant recipients.
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