Reginald Greene

Treatment of Invasive Aspergillosis with Posaconazole in Patients Who Are Refractory to or Intolerant of Conventional Therapy: An Externally Controlled Trial

BACKGROUND Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. METHODS We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. RESULTS Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. CONCLUSIONS Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.

Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign.

BACKGROUND Computed tomography (CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which is an early sign of invasive pulmonary aspergillosis (IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life-threatening infection. METHODS Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. RESULTS At presentation, most patients (94%) had > or =1 macronodules, and many (61%) also had halo signs. Other imaging findings at presentation, including consolidations (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent signs (10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment (52% vs. 29%; P<.001) and greater survival to 84 days (71% vs. 53%; P<.01) than did patients who presented with other imaging findings. CONCLUSIONS Most patients presented with a halo sign and/or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival.

The radiological spectrum of pulmonary aspergillosis

Imaging findings in the pulmonary aspergilloses can answer important clinical questions. Steroid-responsive chronic asthma due to allergic bronchopulmonary aspergillosis can be differentiated from simple asthma by computed tomography (CT) evidence of extensive and severe central bronchiectasis, mucoid impaction, or small airways lesions. The simple aspergilloma can be differentiated from the complex aspergilloma by the absence of: constitutional symptoms, para-cystic lung opacities, cyst expansion, or progressive pleural thickening. The CT halo sign is a transient finding that can provide a probable diagnosis of early invasive pulmonary aspergillosis in patients who are at extraordinarily high risk of the infection. Patients with a halo sign at baseline are more likely to have a satisfactory treatment response than those without this indicator.

Benign Blood Vascular Tumors of the Mediastinum

The authors present 4 new cases and review 77 previously reported cases of benign blood vascular tumors of the mediastinum. The vast majority are hemangiomas (90%), occur in the first four decades of life (75 %), and arise in the anterior mediastinum (68 %). Compression and/or invasion of adjacent structures is not uncommon. Concomitant extrathoracic extension (2%) and multiple sites of involvement (2%) are rare. The tumors are smoothly outlined, occasionally tabulated and can be accurately identified when phleboliths are present (10%).

A comparison of digitized storage phosphors and conventional mammography in the detection of malignant microcalcifications.

The detectability of malignant tumor-derived microcalcifications with conventional mammography was compared to that with digital images (2000 X 2510 pixels by 10 bits) derived from a storage phosphor-based digital radiography system capable of 5 line pair/mm resolution at identical exposure factors (30 kVp, 250 mAs, 65 cm film-focus distance). Microcalcifications (50-800 microns in diameter) were randomly superimposed on a preserved human breast specimen. ROC analysis based on 480 observations made by four readers indicated that the ability to detect the calcifications with digital images (ROC area = 0.871 +/- 0.066) was equivalent to conventional mammography (ROC area = 0.866 +/- 0.075) despite lower spatial resolution. With digital mammography, 62% of all clusters were correctly localized, but only 23.6% of the individual calcifications were counted. With conventional mammography 61% of all clusters were correctly localized, but significantly more of the individual calcifications (31.5%) were counted.

Spatial Heterogeneity of Lung Perfusion Assessed with 13N PET as a Vascular Biomarker in Chronic Obstructive Pulmonary Disease

Although it is known that structural and functional changes in the pulmonary vasculature and parenchyma occur in the progress of chronic obstructive pulmonary disease (COPD), information is limited on early regional perfusion (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r) alterations. Methods: We studied 6 patients with mild or moderate COPD and 9 healthy subjects (6 young and 3 age-matched). The PET 13NN-labeled saline injection method was used to compute images of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r and regional ventilation (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{V}}}\) \end{document}r). Transmission scans were used to assess regional density. We used the squared coefficient of variation to quantify \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r heterogeneity and length-scale analysis to quantify the contribution to total perfusion heterogeneity of regions ranging from less than 12 to more than 108 mm. Results: Perfusion distribution in COPD subjects showed larger \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r heterogeneity, higher contribution from large length scales and lower contribution from small length scales, and larger heterogeneity of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r normalized by tissue density than did healthy subjects. Dorsoventral gradients of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{V}}}\) \end{document}r were present in healthy subjects, with larger ventilation in dependent regions, whereas no gradient was present in COPD. Heterogeneity of ventilation–perfusion ratios was larger in COPD. Conclusion: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r is significantly redistributed in COPD. \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{Q}}}\) \end{document}r heterogeneity in COPD patients is greater than in healthy subjects, mainly because of the contribution of large lung regions and not because of changes in tissue density or \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\dot{V}}}\) \end{document}r. The assessment of spatial heterogeneity of lung perfusion with 13NN-saline PET may serve as a vascular biomarker in COPD.

High frequency edge enhancement in the detection of fine pulmonary lines. Parity between storage phosphor digital images and conventional chest radiography.

Fine linear structures represent a severe test of the minimum spatial resolution that is needed for digital chest imaging. We studied the comparative observer performance of storage phosphor digital imaging (1760 X 2140 pixel matrix, 10 bits deep), and conventional radiography (Lanex medium screen, Ortho C film) in the detection of simulated fine pulmonary lines superimposed on the normal chest when exposure factors were identical (20mR skin entrance dose at 141 kVp). Receiver operating characteristics analysis of 2160 observations by six readers found that high frequency edge-enhanced digital images (ROC area: 0.78 +/- 0.06) performed better than unenhanced digital images (ROC area: 0.70 +/- 0.07) (P less than 0.01 for paired t-test), and that edge enhanced digital images performed on a par with conventional radiography (ROC area: 0.78 +/- 0.09). We conclude that for the detection of fine linear structures, storage phosphor digital images can perform on a par with higher resolution conventional chest radiographs when a high frequency edge-enhancement algorithm is employed.

Imaging Pulmonary Infection: Classic Signs and Patterns

OBJECTIVE The purposes of this article are to describe common and uncommon imaging signs and patterns of pulmonary infections and to discuss their underlying anatomic and pathophysiologic basis. CONCLUSION Imaging plays an integral role in the diagnosis and management of suspected pulmonary infections and may reveal useful signs on chest radiographs and CT scans. Detected early, these signs can often be used to predict the causative agent and pathophysiologic mechanism and possibly to optimize patient care.

Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behçet disease

Abstract. Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.

Etiology and Management of the Compromised Patient with Fever and Pulmonary Infiltrates

The immunocompromised patient in whom fever and pneumonitis develop presents a formidable challenge to the clinician. A legion of microbial invaders ranging from common viral and bacterial pathogens to exotic fungal and protozoan agents have been reported to cause pulmonary infection in these patients. Given the array of infectious etiologies, it is little wonder that pneumonia is the most frequent cause of fatal infection in the compromised host.1–8 For example, in one large series of 227 renal transplant patients, inflammatory disease of the lung occurred in 20% of patients and was associated with 50% of fatalities.6 Patients with acute leukemia in relapse develop an episode of pneumonia approximately once every 60 days at risk.9 In patients with hematologic malignancy who developed fever and pulmonary infiltrates, the mortality rate (45%) was five times that for such patients with fever alone.10