Diagnostic accuracy of bone SPECT and SPECT/CT imaging in the diagnosis of unilateral condylar hyperplasia: A systematic review and meta-analysis.

Imaging with bone scans plays an important role in the diagnostic path of patients with unilateral condylar hyperactivity or unilateral condylar hyperplasia (UCH). The aim of this study is to perform a systematic review of the diagnostic performance of the bone SPECT and SPECT/CT scan for the diagnosis of UCH. PubMed, SCOPUS and EMBASE were searched electronically to identify diagnostic accuracy studies that assessed the diagnostic value of bone SPECT and SPECT/CT for the diagnosis of UCH, Meta-analyses were performed with Metadisc 1.4 and 2.0. A total of 14 studies, with a total number of 887 patients, were included in the qualitative analysis and 11 studies qualified for meta-analyses. The pooled sensitivity and specificity for the SPECT scan were 0.814 (95 % CI: 0.639-0.915) and 0.774 (95 % CI: 0.655-0.861), for the SPECT/CT scan these were 0.818 (95 % CI: 0.749-0.874) and 0.901 (95 % CI: 0.840-0.945). The summary receiver operating characteristics of the SPECT scan showed an area under the curve of 0.847 (95 % CI: 0.722-0.972) and that of the SPECT/CT scan was 0.928 (95 % CI: 0.876-0.980). CONCLUSION: Both bone SPECT scan and SPECT/CT scan provide a high diagnostic accuracy for UCH. The added value of the SPECT/CT scan is questionable and given the potential disadvantages of the SPECT/CT scan, including the increased radiation dose and costs, the diagnostic modality of first choice in patients with UCH should be a SPECT scan.

Diagnostic performance of SPECT-CT imaging in unilateral condylar hyperplasia.

Nuclear imaging plays an important role in the diagnostic path of patients with unilateral condylar hyperplasia (UCH). The purpose of this study was to determine the performance of single-photon emission computed tomography-computed tomography (SPECT-CT) in a large group of patients with suspected UCH. This study prospectively included 156 patients with a clinical presentation of progressive mandibular asymmetry. All patients underwent 99 mTc-HDP SPECT-CT and extensive baseline and follow-up documentation. The relative activity of the ipsilateral condyle in relation to the contralateral condyle was calculated for both the mean and maximum count, and the diagnostic accuracy of different cut-off values was determined. The area under the receiver operating characteristic curve of the SPECT-CT scan was 0.892 for the mean count and 0.873 for the maximum count. The optimal cut-off of> 8% (SPECT-CT mean count) resulted in a sensitivity of 87.0% and a specificity of 88.6%. SPECT-CT showed good diagnostic performance in UCH; however the benefit of the CT scan is questionable and the potential disadvantages have to be weighed against the benefits when compared to standard SPECT scanning. When using SPECT-CT in the diagnostic path in UCH, a mean value cut-off of>8% for the relative activity between the condyles is most accurate.

The Accuracy of Imaging Techniques in the Assessment of Periprosthetic Hip Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Various imaging techniques are used for excluding or confirming periprosthetic hip infection, but there is no consensus regarding the most accurate technique. The objective of this study was to determine the accuracy of current imaging modalities in diagnosing periprosthetic hip infection. METHODS: A systematic review and meta-analysis of the literature was conducted with a comprehensive search of MEDLINE and Embase to identify clinical studies in which periprosthetic hip infection was investigated with different imaging modalities. The sensitivity and specificity of each imaging technique were determined and compared with the results of microbiological and histological analysis, intraoperative findings, and clinical follow-up of >6 months. RESULTS: A total of 31 studies, published between 1988 and 2014, were included for meta-analysis, representing 1,753 hip prostheses. Quality assessment of the included studies identified low concerns with regard to external validity but more concerns with regard to internal validity including risk of bias (>50% of studies had insufficient information). No meta-analysis was performed for radiography, ultrasonography, computed tomography, and magnetic resonance imaging because of insufficient available clinical data. The pooled sensitivity and specificity were 88% (95% confidence interval [CI], 81% to 94%) and 92% (95% CI, 88% to 96%), respectively, for leukocyte scintigraphy; 86% (95% CI, 80% to 90%) and 93% (95% CI, 90% to 95%) for fluorodeoxyglucose positron emission tomography (FDG PET); 69% (95% CI, 58% to 79%) and 96% (95% CI, 93% to 98%) for combined leukocyte and bone marrow scintigraphy; 84% (95% CI, 70% to 93%) and 75% (95% CI, 66% to 82%) for antigranulocyte scintigraphy; and 80% (95% CI, 72% to 86%) and 69% (95% CI, 64% to 73%) for bone scintigraphy. CONCLUSIONS: Of the currently used imaging techniques, leukocyte scintigraphy has satisfactory accuracy in confirming or excluding periprosthetic hip infection. Although not significantly different, combined leukocyte and bone marrow scintigraphy was the most specific imaging technique. FDG PET has an appropriate accuracy in confirming or excluding periprosthetic hip infection, but may not yet be the preferred imaging modality because of limited availability and relatively higher cost. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

(18)F-fluoride-PET for dynamic in vivo monitoring of bone formation in multiple myeloma.

BACKGROUND: Bone disease in multiple myeloma is characterized by reduced bone formation. The gold standard of bone formation is the mineral apposition rate (MAR), an invasive technique reflecting bone formation at a single site. We compared (18)F-fluoride-PET with the MAR in myeloma patients. METHODS: Bone formation was measured before and after bortezomib treatment by determination of the MAR in iliac bone marrow biopsies and the measurement of (18)F-uptake. RESULTS: The inter- and intra-individual variations in (18)F-uptake (SUVA50%) were pronounced as 33.50 (range 4.42 to 37.92) and 27.18 (range 4.00 to 31.18), respectively. A significant correlation between the MAR and (18)F-uptake was found (r = 0.80, p = 0.017). There was a heterogeneous response after treatment varying from -2.20 to 4.53. CONCLUSIONS: Iliac (18)F-uptake was associated with the local MAR in myeloma patients. Furthermore, (18)F-fluoride-PET demonstrated the heterogeneity of in vivo bone formation, enabling monitoring during treatment.

The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function.

PURPOSE: Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function. METHODS: A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [(15)O]H2O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow. RESULTS: Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg×ml(-1)×min(-1)×g(-1), p < 0.01) as compared to nonobese patients. Male gender (ß = 40.7, p < 0.001), BMI (ß = 1.61, p < 0.001), smoking (ß = 6.29, p = 0.03) and EAT volume (ß = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR. CONCLUSION: EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors.

Microcomputed tomographic analysis of human condyles in unilateral condylar hyperplasia: increased cortical porosity and trabecular bone volume fraction with reduced mineralisation.

Unilateral condylar hyperplasia or hyperactivity is a disorder of growth that affects the mandible, and our aim was to visualise the 3-dimensional bony microstructure of resected mandibular condyles of affected patients. We prospectively studied 17 patients with a clinical presentation of progressive mandibular asymmetry and an abnormal single-photon emission computed tomographic (SPECT) scan. All patients were treated by condylectomy to arrest progression. The resected condyles were scanned with micro-CT (18 µm resolution). Rectangular volumes of interest were selected in 4 quadrants (lateromedial and superoinferior) of the trabecular bone of each condyle. Variables of bone architecture (volume fraction, trabecular number, thickness, and separation, degree of mineralisation, and degree of structural anisotrophy) were calculated with routine morphometric software. Eight of the 17 resected condyles showed clear destruction of the subchondral layer of cortical bone. There was a significant superoinferior gradient for all trabecular variables. Mean (SD) bone volume fraction (25.1 (6) %), trabecular number (1.69 (0.26) mm(-1)), trabecular thickness (0.17 (0.03) mm), and degree of mineralisation (695.39 (39.83) mg HA/cm(3)) were higher in the superior region. Trabecular separation (0.6 (0.16) mm) and structural anisotropy (1.84 (0.28)) were higher in the inferior region. The micro-CT analysis showed increased cortical porosity in many of the condyles studied. It also showed a higher bone volume fraction, greater trabecular thickness and trabecular separation, greater trabecular number, and less mineralisation in the condyles of the 17 patients compared with the known architecture of unaffected mandibular condyles.

Comparison of different analytical methods used for analyzing SPECT scans of patients with unilateral condylar hyperactivity.

This study aimed to compare different analytical methods and identify the optimal analysis method to distinguish patients with unilateral condylar hyperactivity (UCH) from those with inactive condyles. Single-photon emission computed tomography (SPECT) scans of patients with progressive and nonprogressive mandibular asymmetry (each group, n=26), were analyzed using the region of interest technique. Sensitivity, specificity and receiver operating characteristic (ROC) curves were calculated for the different analytic methods. The ROC curve illustrates that UCH can be diagnosed significantly better by determining the percentile bone activity in both condyles. The area under the curve (AUC) of the percentile comparison between the affected and contralateral condyles was 0.93+/-0.04, that for the condyle/clivus ratio was 0.75+/-0.07 and for the condyle/cervical spine (CS) ratio 0.57+/-0.08. Sensitivity for the condyle/clivus ratio was 65% and specificity 61%. Sensitivity for the condyle/CS ratio was 85% and specificity 31%. For the percentile difference of the condyles, sensitivity and specificity were 88%. For UCH patients, direct comparison of bone activity between the affected and contralateral condyle in SPECT scans is the analysis method of choice. Comparison of condylar bone activity to reference bone activity does not have additional value in the diagnosis of UCH.

Sentinel node detection in patients with thyroid carcinoma: a meta-analysis.

OBJECTIVE: This study was designed to review the diagnostic performance of sentinel node (SN) detection for assessment of the nodal status in thyroid carcinoma patients and to determine the technique (using blue dye or Technetium-99m colloid (99mTc) that demonstrated the highest success rate with regard to the detection rate and sensitivity. METHODS: A comprehensive computer literature search of studies published in English language through December 2007 and regarding SN procedures in patients with thyroid disorders was performed in MEDLINE. Pooled values regarding the SN detection rate and the pooled sensitivity values of the SN procedure were presented with a 95% confidence interval (CI) for the different SN detection techniques. RESULTS: Ultimately, we identified 14 studies comprising a total of 457 patients. Of these, ten studies (n = 329 patients) used the blue dye technique with a pooled SN detection of 83% (95% CI, 79-87%). The remaining four studies (n = 128) used 99mTc-colloid with a pooled SN detection of 96% (95% CI, 91-99%; p < 0.05 vs. blue dye technique). CONCLUSION: In patients with suspected thyroid carcinoma, SN biopsy demonstrated a higher SN detection rate when 99mTc was used (96%) instead of the blue dye technique (83%).

Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery.

BACKGROUND: The optimal type of fluid for treating hypovolaemia without evoking pulmonary oedema is still unclear, particularly in the presence of pulmonary vascular injury, as may occur after cardiac and major vascular surgery. METHODS: In a single-centre, prospective, single-blinded clinical trial 67 mechanically ventilated patients were randomly assigned to receive saline, gelatin 4%, HES 6% or albumin 5%, according to a 90 min fluid loading protocol with target central venous pressure of 13 and pulmonary capillary wedge pressure of 15 mm Hg, within 3 h after cardiac or major vascular surgery. Before and after the protocol, we recorded haemodynamics and ventilatory variables and took chest radiographs. The pulmonary vascular injury was evaluated using the 67Ga-transferrin pulmonary leak index (PLI) and extravascular lung water (EVLW). Plasma colloid osmotic pressure (COP) was determined and the lung injury score (LIS) was calculated. RESULTS: More saline was infused than colloid solutions (P<0.005). The COP increased in the colloid groups and decreased in patients receiving saline. Cardiac output increased more in the colloid groups. At baseline, PLI and EVLW were above normal in 60 and 30% of the patients, with no changes after fluid loading, except for a greater PLI decrease in HES than in gelatin-loaded patients. The oxygenation ratio improved in all groups. In the colloid groups, the LIS increased, because of a decrease in total respiratory compliance, probably associated with an increase in intrathoracic plasma volume. CONCLUSIONS: Provided that fluid overloading is prevented, the type of fluid used for volume loading does not affect pulmonary permeability and oedema, in patients with acute lung injury after cardiac or major vascular surgery, except for HES that may ameliorate increased permeability. During fluid loading, changes in LIS (and respiratory compliance) do not represent changes in pulmonary permeability or oedema.

The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis.

BACKGROUND: A variety of diagnostic imaging techniques is available for excluding or confirming chronic osteomyelitis. Until now, an evidence-based algorithmic model for choosing the most suitable imaging technique has been lacking. The objective of this study was to determine the accuracy of current imaging modalities in the diagnosis of chronic osteomyelitis. METHODS: A systematic review and meta-analysis of the literature was conducted with a comprehensive search of the MEDLINE, EMBASE, and Current Contents databases to identify clinical studies on chronic osteomyelitis that evaluated diagnostic imaging modalities. The value of each imaging technique was studied by determining its sensitivity and specificity compared with the results of histological analysis, findings on culture, and clinical follow-up of more than six months. RESULTS: A total of twenty-three clinical studies in which the accuracy was described for radiography (two studies), magnetic resonance imaging (five), computed tomography (one), bone scintigraphy (seven), leukocyte scintigraphy (thirteen), gallium scintigraphy (one), combined bone and leukocyte scintigraphy (six), combined bone and gallium scintigraphy (three), and fluorodeoxyglucose positron emission tomography (four) were included in the review. No meta-analysis was performed with respect to computed tomography, gallium scintigraphy, and radiography. Pooled sensitivity demonstrated that fluorodeoxyglucose positron emission tomography was the most sensitive technique, with a sensitivity of 96% (95% confidence interval, 88% to 99%) compared with 82% (95% confidence interval, 70% to 89%) for bone scintigraphy, 61% (95% confidence interval, 43% to 76%) for leukocyte scintigraphy, 78% (95% confidence interval, 72% to 83%) for combined bone and leukocyte scintigraphy, and 84% (95% confidence interval, 69% to 92%) for magnetic resonance imaging. Pooled specificity demonstrated that bone scintigraphy had the lowest specificity, with a specificity of 25% (95% confidence interval, 16% to 36%) compared with 60% (95% confidence interval, 38% to 78%) for magnetic resonance imaging, 77% (95% confidence interval, 63% to 87%) for leukocyte scintigraphy, 84% (95% confidence interval, 75% to 90%) for combined bone and leukocyte scintigraphy, and 91% (95% confidence interval, 81% to 95%) for fluorodeoxyglucose positron emission tomography. The sensitivity of leukocyte scintigraphy in detecting chronic osteomyelitis in the peripheral skeleton was 84% (95% confidence interval, 72% to 91%) compared with 21% (95% confidence interval, 11% to 38%) for its detection of chronic osteomyelitis in the axial skeleton. The specificity of leukocyte scintigraphy in the axial skeleton was 60% (95% confidence interval, 39% to 78%) compared with 80% (95% confidence interval, 61% to 91%) for the peripheral skeleton. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography has the highest diagnostic accuracy for confirming or excluding the diagnosis of chronic osteomyelitis. Leukocyte scintigraphy has an appropriate diagnostic accuracy in the peripheral skeleton, but fluorodeoxyglucose positron emission tomography is superior for detecting chronic osteomyelitis in the axial skeleton.

Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema.

BACKGROUND: Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate. METHODS: A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer. RESULTS: The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without. CONCLUSIONS: After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one-half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis.

In this meta-analysis we included 32 English-language articles published between January 1975 and June 2004 on the diagnostic performance of plain radiography, subtraction arthrography, nuclear arthrography and bone scintigraphy in detecting aseptic loosening of the femoral component, using criteria based on the Cochrane systematic review of screening and diagnostic tests. The mean sensitivity and specificity were, respectively, 82% (95% confidence interval (CI) 76 to 87) and 81% (95% CI 73 to 87) for plain radiography and 85% (95% CI 75 to 91) and 83% (95% CI 75 to 89) for nuclear arthrography. Pooled sensitivity and specificity were, respectively, 86% (95% CI 74 to 93) and 85% (95% CI 77 to 91) for subtraction arthrography and 85% (95% CI 79 to 89) and 72% (95% CI 64 to 79) for bone scintigraphy. Although the diagnostic performance of the imaging techniques was not significantly different, plain radiography and bone scintigraphy are preferred for the assessment of a femoral component because of their efficacy and lower risk of patient morbidity.

Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission tomography in recurrent melanoma.

The purpose of this study was to assess the reproducibility and clinical impact of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with (suspected) recurrent melanoma. The clinical value of PET was prospectively measured in 58 consecutive patients referred for PET because of unresolved clinical questions after conventional work-up. Diagnostic understanding and therapy choice by referring physicians were evaluated before, directly after, and 6 months after PET. Observer agreement of PET readings was measured with respect to various parameters (interpretation, number and localization of lesions, 'clinically decisive' metastases), using intra-class correlation coefficients. FDG PET improved diagnostic understanding in 33 cases (57%). In six patients (10%), diagnostic understanding was solely based on PET information. According to the attending clinicians, PET contributed to a positive change of planned treatment in 23 patients (40%) and increased confidence in the chosen treatment in 23 (40%). Observer agreement of PET readings was very high (intra-class correlation coefficients were between 0.87 and 0.94). The diagnostic value related especially to the whole-body scan technique and the superior specificity, compared to conventional work-up. It is concluded that, in problematical cases with (suspected) recurrent melanoma, 18F-FDG PET had considerable impact on diagnostic understanding and management. Together with the excellent observer reliability, these results justify further studies to determine the optimal place of PET in routine diagnostic algorithms in recurrent melanoma.

The 67gallium-transferrin pulmonary leak index in patients at risk for the acute respiratory distress syndrome.

OBJECTIVE: To determine the occurrence and clinical importance of increased pulmonary microvascular permeability in patients at risk for acute respiratory distress syndrome (ARDS). DESIGN: Prospective, cohort study. SETTING: Medical and surgical intensive care unit (ICU) and department of nuclear medicine of a university hospital. PATIENTS: Thirteen consecutive patients at risk for ARDS with sepsis (n = 4), multiple trauma (n = 3), hemorrhagic pancreatitis (n = 5), and near-drowning (n = 1), admitted into the ICU. All patients were intubated and mechanically ventilated in the course of the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 67gallium-transferrin pulmonary leak index (PLI) (upper limit of normal in patients scheduled for major surgery 14.7 x 10(-3)/min) was measured within 24 hrs of admission. In addition, radiographic, gas exchange, and ventilatory variables allowing calculation of the Lung Injury Score, were obtained on the day of the PLI (day 0) and from days 1 to 7. Patients were followed until discharge or death in the ICU. No patient developed ARDS (Lung Injury Score of >2.5 in the absence of congestive heart failure) and all but four patients survived. The PLI (median [range]) was 18.5 (7.0 to 81.9) x 10(-3)/min and was supranormal in 8 of 13 patients (p < .001 vs. normal). The PLI correlated with the Simplified Acute Physiology Score (SAPS) II (r[s] = .79, p < .01) and was higher in nonsurvivors than in survivors (p < .05), with a tendency for a higher SAPS II in the nonsurvivors. On day 0, the chest radiographic score of alveolar abnormalities was 0 (0 to 4), indicating absence of radiographic abnormalities in most patients. Also, on day 0, the median PaO2/FIO2 ratio was 257 (range 119 to 460). The Lung Injury Score on day 0 was 1.0 (0 to 2.0), which is consistent with mild acute lung injury in all but one patient. In the course of time, the oxygenation ratio was lower and the Lung Injury Score was higher in nonsurvivors than in survivors, particularly for the Lung Injury Score on days 1 and 2. The PLI correlated directly with the Lung Injury Score on days 0 and 1. On day 0, the PLI correlated inversely with the oxygenation ratio. On the last evaluable day of the first ICU week, the PLI correlated directly with the Lung Injury Score and the positive end-expiratory pressure level. The duration of mechanical ventilation tended to be longer in patients with a supranormal PLI. CONCLUSIONS: In this small population, 61% of patients at risk for ARDS and with only mild respiratory changes exhibited increased microvascular permeability in the lungs at ICU admission. Increased permeability may be an early marker of acute lung injury and its clinical features, and may be associated with a relatively complicated respiratory course during the first week after admission, even in the absence of progression to ARDS. Finally, increased pulmonary microvascular permeability may be associated with severe underlying disease and ultimate mortality in the ICU.

Acute lung injury after aortic surgery: the relation between lung and leg microvascular permeability to 111indium-labelled transferrin and circulating mediators.

BACKGROUND: Aortic surgery is a risk factor for acute lung injury and this may relate to ischaemia/reperfusion (I/R) of the lower body and release of inflammatory mediators. The aim of this study was to define the changes in microvascular protein permeability and circulating inflammatory mediators after aortic surgery. METHODS: In 11 consecutive patients who underwent elective aortic surgery microvascular permeability in lung and leg was measured before and a median of 2.8 hours after completion of surgery using 111indium (In)-labelled transferrin and 99mtechnetium (Tc)-labelled red blood cells, yielding a protein leak index (PLI) that is specific for protein permeability. Circulating leucocyte counts and levels of inflammatory mediators were determined. RESULTS: In the lung the PLI rose from a median of 0.6 (range -0.5 to 2.2) x 10(-3)/min before surgery to 5.4 (-2.3 to 33.5) x 10(-3)/min after surgery, and in the leg from 0.3 (-1.6 to 1.7) x 10(-3)/min to 5.0 (1.0 to 27.8) x 10(-3)/min. The increase in PLI in the lung was related to that in the leg. Levels of activated complement C3a and tumour necrosis factor-alpha did not change, but levels of interleukin (IL)-6, IL-8 and elastase-alpha 1-antitrypsin increased. After surgery there was slight neutrophilia and the leucocyte counts were inversely related to the IL-8 level. The rise in lung but not in leg PLI was greatest in patients with the highest IL-8 levels and the lowest leucocyte counts. CONCLUSIONS: Early after aortic surgery microvascular protein permeability increases in the leg and lung. Leg I/R injury may result in neutrophil activation and release of IL-8, which may induce neutrophil sequestration and subsequently increased pulmonary microvascular permeability. These findings may help to explain the occurrence of acute lung injury after I/R in man.

The inflammatory response to vascular surgery-associated ischaemia and reperfusion in man: effect on postoperative pulmonary function.

OBJECTIVES: To characterise the inflammatory response to vascular surgery and ischaemia/reperfusion (I/R) in man, regarding release of inflammatory mediators, recruitment and activation of neutrophils, and their relation to postoperative pulmonary function. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Circulating neutrophil counts and plasma levels of elastase-alpha 1-antitrypsin (AT), a neutrophil degranulation product, were measured before and approx. 2.5 h (group 1, n = 19) after elective abdominal aortic surgery, and approx. 2.9 h after elective peripheral vascular surgery (group 2, n = 6), together with concentrations of neutrophil agonists, including activated complement (C3a), secretory phospholipase A2 (sPLA2), tumor necrosis factor (TNF-alpha), interleukin (IL)-6, IL-8 and granulocyte colony-stimulating factor (G-CSF). At the time of blood sampling, respiratory variables allowing computation of the lung injury score (LIS) were obtained in patients admitted after surgery in the intensive care unit (ICU), i.e. all group 1 patients and one group 2 patient. RESULTS: Median (range) neutrophil counts rose by 80% (-28-208) and 90% (10-147) in groups 1 and 2, respectively (n.s. between groups). The increase (p < 0.05) in elastase-alpha 1-AT level was 121% (-5-439) in group 1 and 82% (18-792) in group 2 (n.s. between groups). There was a rise (p < 0.05) in C3a level by 93% (-42-751) and of sPLA2 level by 68% (-40-1400) after surgery for the groups together (n.s. between groups), and the rise of the elastase-alpha 1-AT related to that of the C3a levels. IL-6 and G-CSF concentrations increased more in group 1 than 2. The IL-8 concentration increased in group 1 only, and TNF-alpha was unchanged in all groups. In ICU patients, the LIS related to the postoperative rise in IL-6 level only, even though the rise in plasma concentrations of cytokines interrelated. No patient developed ARDS and all survived. CONCLUSIONS: Vascular surgery and I/R in man activates complement, releases cytokines (except for TNF-alpha), and induces neutrophil recruitment and degranulation, which may primarily depend on complement activation. In contrast to the latter, the release of cytokines may depend on the extent of I/R and may contribute to transient pulmonary dysfunction after extensive I/R.

Systemic coagulation and fibrinolysis in patients with or at risk for the adult respiratory distress syndrome.

The authors sought to evaluate the pathogenetic and prognostic role of a procoagulant and hypofibrinolytic state in the adult respiratory distress syndrome (ARDS). Twenty-two consecutive patients admitted to the intensive care unit (ICU) for respiratory monitoring (n = 2) or mechanical ventilation (n = 20) were studied, of whom 13 had ARDS and 9 were at risk for the syndrome. Plasma levels of thrombin-antithrombin III complexes (TAT), the plasmin-alpha2-antiplasmin complexes (PAP), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were measured within 48 h after admission, together with respiratory variables allowing computation of the lung injury score (LIS), and pulmonary microvascular permeability [67Gallium-transferrin pulmonary leak index (PLI)], as measures of pulmonary dysfunction. Blood was also sampled 6-hourly until 2 days after admission. The LIS and PLI were higher in ARDS than at risk patients, in the presence of similar systemic morbidity and mortality. TAT complexes were elevated in a minority of patients of both groups, whereas the PAP, tPA and PAI levels were elevated above normal in the majority of ARDS and at risk patients, but groups did not differ. Neither circulating coagulation nor fibrinolysis variables correlated to either LIS or PLI. Furthermore, the course of haemostatic variables did not relate to outcome. These data indicate that systemic activation of coagulation and impaired fibrinolysis do not play a major role in ARDS development and outcome in patients with acute lung injury.

Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery.

STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial study. SETTING: Department of nuclear medicine and intensive care units of a university hospital. PATIENTS: Twelve consecutive patients were studied, before and immediately after elective cardiac surgery using CPB (group 1), and 4 consecutive, artificially ventilated patients with acute cardiogenic pulmonary edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both lungs were measured, using two mobile probes at the bedside, of intravenously injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc-labeled red blood cells to account for pulmonary blood volume. From data recorded in time (1 h), a pulmonary leak index (PLI), the time constant of transport of 67Ga from the intravascular to the extravascular space of the lung, was calculated and values for both lungs were averaged. In group 1, the PLI (.10(-3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery (p < 0.01) and changes directly related to the duration of CPB. In four patients with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded 2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to changes in arterial WBC, which, in turn, inversely related to CPB duration. The PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No patient developed alveolar pulmonary edema on chest radiograph. In group 2, the PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI). CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as assessed by 67Ga kinetics using a bedside detection technique, in some cardiac surgery patients with prolonged CPB. This leak may reflect pulmonary vascular injury and increased permeability, following activation of leukocytes by CPB and subsequent pulmonary sequestration, rather than increased filtration through pressure factors. It may contribute to impaired gas exchange, even in the absence of manifest alveolar edema of the lungs, after surgery.