Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture.

Paramount for the generation of auricular structures of clinically-relevant size is the acquisition of a large number of cells maintaining an elastic cartilage phenotype, which is the key in producing a tissue capable of withstanding forces subjected to the auricle. Current regenerative medicine strategies utilize chondrocytes from various locations or mesenchymal stromal cells (MSCs). However, the quality of neo-tissues resulting from these cell types is inadequate due to inefficient chondrogenic differentiation and endochondral ossification, respectively. Recently, a subpopulation of stem/progenitor cells has been identified within the auricular cartilage tissue, with similarities to MSCs in terms of proliferative capacity and cell surface biomarkers, but their potential for tissue engineering has not yet been explored. This study compared the in vitro cartilage-forming ability of equine auricular cartilage progenitor cells (AuCPCs), bone marrow-derived MSCs and auricular chondrocytes in gelatin methacryloyl (gelMA)-based hydrogels over a period of 56 d, by assessing their ability to undergo chondrogenic differentiation. Neocartilage formation was assessed through gene expression profiling, compression testing, biochemical composition and histology. Similar to MSCs and chondrocytes, AuCPCs displayed a marked ability to generate cartilaginous matrix, although, under the applied culture conditions, MSCs outperformed both cartilage-derived cell types in terms of matrix production and mechanical properties. AuCPCs demonstrated upregulated mRNA expression of elastin, low expression of collagen type X and similar levels of proteoglycan production and mechanical properties as compared to chondrocytes. These results underscored the AuCPCs' tissue-specific differentiation potential, making them an interesting cell source for the next generation of elastic cartilage tissue-engineered constructs.

Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease.

Interstitial lung disease is a common manifestation of rheumatoid arthritis; however, little is known about factors that influence its prognosis. The aim of the present study was to determine whether or not the usual interstitial pneumonia pattern found on high-resolution computed tomography (HRCT) is of prognostic significance in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Patients with RA-ILD were identified retrospectively (n = 82). The relationship of a definite usual interstitial pneumonia pattern on HRCT to survival was determined and compared to that in a cohort of patients with radiologically diagnosed idiopathic pulmonary fibrosis (n = 51). A definite usual interstitial pneumonia pattern was seen in 20 (24%) out of 82 patients with RA-ILD. These patients showed worse survival than those without this pattern (median survival 3.2 versus 6.6 yrs), and a similar survival to those with idiopathic pulmonary fibrosis. On multivariate analysis, a definite usual interstitial pneumonia pattern on HRCT was associated with worse survival (hazard ratio of 2.3). Analysis of specific HRCT features demonstrated that traction bronchiectasis and honeycomb fibrosis were associated with worse survival (hazard ratio of 2.6 and 2.1, respectively). Female sex (hazard ratio of 0.30) and a higher baseline diffusing capacity of the lung for carbon monoxide (hazard ratio of 0.96) were associated with better survival. A definite usual interstitial pneumonia pattern on HRCT has important prognostic implications in RA-ILD.

Neurofibromatosis-associated lung disease: a case series and literature review.

An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis. A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed. A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%). In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.

Acute rejection following lung transplantation: limitations in accuracy of thin-section CT for diagnosis.

PURPOSE: To evaluate the sensitivity, specificity, predictive values, and accuracy of thin-section computed tomography (CT) for the diagnosis of acute rejection following lung transplantation and to determine whether any individual CT abnormalities are associated with histopathologically proved acute rejection. MATERIALS AND METHODS: Thin-section CT studies from 64 lung transplant recipients were retrospectively reviewed. CT studies were temporally correlated with various grades of biopsy-proved acute rejection (n = 34); 30 other CT studies were from a control group with no histopathologic evidence of acute rejection. Acute rejection was diagnosed as present or absent, and the diagnostic was calculated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT for the diagnosis of acute rejection were as follows: 35%, 73%, 60%, 50%, 53%, respectively. No individual CT finding was significantly associated with acute rejection. The sensitivity of CT for the detection of various grades of acute rejection was 17% for grade A1, 50% for grade A2, and 20% for grade A3. The combination of volume loss and septal thickening, with or without pleural effusion, was never seen in the absence of acute rejection. CONCLUSION: Thin-section CT has limited accuracy for the diagnosis of acute rejection following lung transplantation, and no individual CT finding is significantly associated with this diagnosis.

Multidetector-row spiral computed tomography in the diagnosis of thoracic diseases.

Since its introduction in 1992, spiral computed tomography (CT) scanners constructed with a single row of detectors have revolutionized imaging of thoracic diseases. Current state-of-the-art models use up to 16 detectors and are capable of acquiring 4 contiguous slices of data with each gantry rotation; systems with 8 data acquisition units (and more) are currently in development. The principal advantages offered by these systems are increased scanning speed and the ability to obtain volumetric data in high resolution. These features enable imaging with enhanced contrast concentration, decreased contrast load, decreased respiratory and cardiac motion artifact, and multiplanar and 3-dimensional reconstruction capabilities. Herein we first review the technical aspects of multidetector spiral CT scanning. The arrangement and various combinations of the detector rows are discussed. Key scanning variables, including collimation (slice thickness), pitch (the rate of table travel per gantry rotation divided by the beam collimation), and gantry speed, are briefly addressed in the context of their interrelationships. Comparison is made with single-detector-row systems to emphasize the superior scanning speed and resolution. We then discuss the various clinical applications of multidetector spiral CT, including CT pulmonary angiography, CT aortography, virtual bronchoscopy, and multiplanar and 3-dimensional reconstructions.

Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series.

Fourteen of 400 consecutive patients having high-resolution computed tomography (HRCT) with expiratory images showed findings of infiltrative lung disease on inspiratory HRCT and air trapping on expiratory CT. Diagnoses included hypersensitivity pneumonitis, sarcoidosis, atypical infection, and pulmonary edema. The extent of infiltrative abnormalities and air trapping were correlated with pulmonary function tests (PFT) in 11 patients. PFT indicated a mixed pattern in five, an obstructive pattern in three, and a restrictive pattern in three. Forced expiratory volume (FEV) in 1 second/forced vital capacity (FVC) correlated significantly with the extent of air-trapping (r = 0.60; p = 0.05). The extent of infiltrative abnormalities correlated significantly and negatively with forced vital capacity (r = -0.82, p = 0.002), FEV1 (r = -0.59, p = 0.05), total lung capacity (TLC) (r = -0.67, p = 0.05), and DLCO (r = -0.75, p = 0.02). Findings of lung infiltration on inspiratory HRCT scans and air trapping on expiratory CT correlated respectively with PFT measures of restrictive and obstructive lung disease.

Minute pulmonary meningothelial-like nodules: thin-section CT appearance.

Minute pulmonary meningothelial-like nodules are often incidentally discovered during pathologic evaluation of pulmonary parenchymal specimens. These lesions were once thought to represent pulmonary chemodectomas, but pathological studies have shown that they are not of neuroendocrine origin. Minute pulmonary meningothelial-like nodules are benign, perhaps reactive in nature, but are occasionally found in association with lung carcinoma. They may appear as randomly distributed well-defined micronodules on thin-section chest CT, and thus may simulate metastatic disease when associated with lung carcinoma.

Comparison between MR imaging and 99mTc MIBI scintigraphy in the evaluation of recurrent of persistent hyperparathyroidism.

PURPOSE: To compare the sensitivity and positive predictive value of magnetic resonance (MR) imaging and technetium 99m 2-methoxyisobutyl-isonitrile (MIBI) scintigraphy for the detection of hyperfunctioning parathyroid tissue when used alone and in combination in a large patient population with recurrent or persistent hyperparathyroidism (HPT). MATERIALS AND METHODS: In 98 consecutive patients with biochemically proved recurrent or persistent HPT after surgery, MR imaging and 99mTc MIBI study findings were retrospectively reviewed and compared with surgical and histopathologic findings. The sensitivity and positive predictive value of MR imaging and 99mTc MIBI scintigraphy were compared with each other and in combination. RESULTS: In these patients, 130 abnormal parathyroid glands were identified at surgery. The sensitivity and positive predictive value of MR imaging were 82% (95% CI: 75%, 89%) and 89%, respectively; those for (99m)Tc MIBI scintigraphy were 85% (95% CI: 79%, 91%) and 89%. No significant difference was found between MR imaging and 99mTc MIBI scintigraphy for sensitivity (P =.7). The sensitivity and positive predictive value for the detection of abnormal parathyroid tissue on a per-gland basis increased to 94% (95% CI: 90%, 98%) and 98%, respectively, when only one of the two tests was required to be positive. CONCLUSION: MR imaging and 99mTc MIBI scintigraphy have similarly good sensitivity and positive predictive value for the detection of hyperfunctioning parathyroid tissue in patients after surgery. The combination of the two tests provided a substantial increase in sensitivity and positive predictive value.

Hypersensitivity pneumonitis: patterns on high-resolution CT.

Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, is caused by inhalation of specific environmental organic antigens. This disease may have typical high-resolution CT findings that, in the appropriate clinical setting, can be sufficiently characteristic to allow a confident diagnosis without the need for a lung biopsy. In this pictorial essay, the high-resolution CT patterns of hypersensitivity pneumonitis are illustrated. The authors emphasize the correlation among the radiologic presentation, functional abnormalities, and pathologic findings.

Early bronchiolitis obliterans following lung transplantation: accuracy of expiratory thin-section CT for diagnosis.

PURPOSE: To evaluate the accuracy of thin-section computed tomography (CT) with expiratory scans in diagnosing early bronchiolitis obliterans after lung transplantation. MATERIALS AND METHODS: Thin-section CT scans were reviewed by two observers blinded to the diagnoses in seven consecutive lung transplant recipients with histopathologically proved bronchiolitis obliterans (group A) and 21 with normal biopsy findings (group B). All patients had normal biopsy and stable pulmonary function test (PFT) results 2-36 weeks prior to CT. Patients with normal biopsy results were placed into subgroups based on abnormal (group B1) or stable (group B2) PFT results. Air-trapping extent on expiratory scans was scored on a 24-point scale. RESULTS: The mean air-trapping score in group A (6.6) was not significantly different from that in group B (4.5, P =. 17). The air-trapping score was significantly higher in groups A and B1 than in group B2 (6.2 and 2.6, respectively; P =.03). The frequency of an air-trapping score of 3 or more in groups A and B1 was significantly higher than that in group B2 (P =.03). By using a score of 3 or more to indicate air trapping, the sensitivity of expiratory CT was 74%, specificity was 67%, and accuracy was 71%. CONCLUSION: Thin-section CT, including expiratory scans, is of limited accuracy in diagnosing early bronchiolitis obliterans after lung transplantation.

Low-dose, dynamic, expiratory thin-section CT of the lungs using a spiral CT scanner.

Seventeen patients with lung transplants were evaluated with inspiratory, postexpiratory, and low-dose, dynamic expiratory thin-section computed tomography (CT). Region of interest measurements were performed on inspiration and expiration images with both techniques, and mean lung attenuation changes between inspiration and expiration images were calculated and compared. Dynamic expiratory thin-section CT resulted in a significantly greater increase in lung attenuation than postexpiratory thin-section CT. Dynamic expiratory thin-section CT may prove useful in the evaluation of patients with lung diseases characterized by air flow obstruction with little increase in patient radiation dose.

Incidental detection of thoracic sarcoidosis on whole-body 18fluorine-2- fluoro-2-deoxy-D-glucose positron emission tomography.

18 Fluorine-2- Fluoro-2-Deoxy-D-Glucose positron emission tomography (18FDG PET) allows imaging of sites with increased metabolic activity. Increased metabolic activity in mediastinal nodes in sarcoidosis has been described. We report the prospective diagnosis of thoracic sarcoidosis on 18FDG PET based on extensive, peripheral, upper lobe parenchymal, and mediastinal nodal tracer uptake.

Clinical and radiographic predictors of the etiology of pulmonary nodules in HIV-infected patients.

STUDY OBJECTIVES: To determine the etiology and the clinical and radiographic predictors of the etiology of pulmonary nodules in a group of HIV-infected patients. DESIGN: Retrospective analysis. SETTING: A large urban hospital in San Francisco, CA. PATIENTS: HIV-infected patients evaluated at San Francisco General Hospital from June 1, 1993, through December 31, 1997, having one or more pulmonary nodules on chest CT. MAIN OUTCOME MEASURES: Three physicians reviewed medical records for clinical data and final diagnoses. Three chest radiologists blinded to clinical data reviewed chest CTs. Univariate and multivariate analyses were performed to determine clinical and radiographic predictors of having an opportunistic infection and the specific diagnoses of bacterial pneumonia and tuberculosis. RESULTS: Eighty seven of 242 patients (36%) had one or more pulmonary nodules on chest CT. Among these 87 patients, opportunistic infections were the underlying etiology in 57 patients; bacterial pneumonia (30 patients) and tuberculosis (14 patients) were the most common infections identified. Multivariate analysis identified fever, cough, and size of nodules < 1 cm on chest CT as independent predictors of having an opportunistic infection. Furthermore, a history of bacterial pneumonia, symptoms for 1 to 7 days, and size of nodules < 1 cm on CT independently predicted a diagnosis of bacterial pneumonia; a history of homelessness, weight loss, and lymphadenopathy on CT independently predicted a diagnosis of tuberculosis. CONCLUSIONS: In HIV-infected patients having one or more pulmonary nodules on chest CT scan, opportunistic infections are the most common cause. Specific clinical and radiographic features can suggest particular opportunistic infections.

Helical CT for the evaluation of suspected acute pulmonary embolism: diagnostic pitfalls.

Helical CT is being increasingly utilized for the evaluation of suspected pulmonary embolism (PE). Proper scan interpretation depends on the awareness of several diagnostic pitfalls that may simulate PE, including normal bronchovascular structures such as pulmonary veins, bronchi, and lymph nodes, technical considerations such as improper bolus timing and streak artifacts, and patient-related factors such as motion artifacts, pulmonary arterial catheters, and vascular shunts. An understanding of these pitfalls facilitates accurate diagnosis.

Measurement of fibroblast proliferative activity in bronchoalveolar lavage fluid in the analysis of obliterative bronchiolitis among lung transplant recipients.

BACKGROUND: Bronchiolitis obliterans occurs in 30% to 80% of lung-transplant recipients and is a direct cause of death in more than 40% of patients with this complication. This study assessed the potential utility of measuring fibroblast-proliferative activity in bronchoalveolar lavage fluid from lung-transplant recipients to better understand the pathogenesis of this process. METHODS: The capacity of bronchoalveolar lavage fluid obtained from transplant recipients, during routine surveillance bronchoscopy, to stimulate the proliferation of human lung fibroblasts in vitro was assessed retrospectively and compared to that of control subjects. For each recipient, a correlation was made between the fibroblast-proliferative activity in serial lavage samples over time and the other modalities employed for detecting post-transplant complications including spirometry, transbronchial lung biopsy, and high-resolution computed tomography. RESULTS: There was a significant difference in fibroblast-proliferative activity between volunteer and transplant recipient groups (p = 0.002). Further, for each transplant recipient, the decline in the forced expired flow rate between 25% and 75% of expired volume (FEF(25%-75%)) was correlated with the mean fibroblast-proliferative activity during the period of this study (r = 0.83; p = 0.04). CONCLUSIONS: A sustained increase in fibroblast-proliferative activity in lavage supernatant precedes both histologic and physiologic evidence of bronchiolitis obliterans. Relative to an increase in fibroblast-proliferative activity or abnormalities in FEF25%-75%, a decrease in forced expiratory volume in 1 second is a late finding.

Imaging evaluation of suspected pulmonary embolism.

Venous thromboembolism (VTE) is a common disorder that is difficult to diagnose clinically but carries significant morbidity and mortality if untreated. Additionally, although demonstrated to be of benefit in cases of proven deep vein thrombosis (DVT) and pulmonary embolism (PE), anticoagulation therapy is not without risk. Because the clinical exam is known to be unreliable for the detection of both DVT and PE, many imaging modalities have been used in the diagnostic imaging algorithm for the detection of VTE, including chest radiography, ventilation/perfusion (V/Q) scintigraphy, pulmonary angiography, and recently, spiral computed tomography (CT) and magnetic resonance imaging (MRI). Chest radiographic findings in acute PE include focal oligemia, vascular enlargement, atelectasis, pleural effusions, and air space opacities representing pulmonary hemorrhage or infarction. The chest radiograph can occasionally be suggestive of PE but is more often nonspecifically abnormal. The main use of the chest radiograph in the evaluation of suspected PE is to exclude entities that may simulate PE and to assist in the interpretation of V/Q scintigraphy. Lower extremity venous compression ultrasonography (CU) is both sensitive and specific for the diagnosis of femoropopliteal DVT, and the value of negative CU results has been established in outcomes studies. However, the reliability of CU for the detection of isolated calf vein thrombosis is not well established, and the clinical significance of such thrombi is debatable. Additional methods such as color and spectral Doppler analysis are also useful in the diagnostic evaluation of DVT but are best considered as adjuncts to the conventional CU examination rather than as primary diagnostic modalities themselves. Compression ultrasonography and Doppler techniques are useful in the evaluation of suspected upper extremity DVT; spectral Doppler waveform analysis is particularly useful to assess for the patency of veins that cannot be directly visualized and compressed with conventional gray-scale sonography. V/Q scintigraphy has been the initial modality obtained in patients suspected of PE for a number of years. Although many studies have investigated the role of V/Q scintigraphy in the evaluation of VTE, the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study has provided the most useful information regarding the utility of V/Q scintigraphy in this setting. A high probability scan interpretation is sufficient justification to institute anticoagulation, and a normal perfusion scan effectively excludes the diagnosis of PE. A normal/near normal scan interpretation also carries a sufficiently low prevalence of angiographically proven PE to withhold anticoagulation. Although the prevalence of PE in the setting of low probability scan interpretations is low and several outcomes studies have demonstrated a benign course in untreated patients with low probability scan results, patients with inadequate cardiopulmonary reserve do not necessarily have good outcomes. Such patients deserve more aggressive evaluation. Patients with intermediate probability scan results have a 20% to 40% prevalence of angiographically proven PE and thus require further investigation. The radionuclide investigation of DVT includes such techniques as radionuclide venography and thrombus-avid scintigraphy. Although these methods have not been as thoroughly evaluated as CU, studies thus far have indicated encouraging results, and further investigations are warranted. Pulmonary angiography has been the gold standard for the diagnosis of PE for decades. Studies have indicated that angiography has probably been underutilized by referring physicians for the evaluation of suspected PE, likely because of the perception of significant morbidity and mortality associated with the procedure. (ABSTRACT TRUNCATED)