Biomarkers for Radiation Biodosimetry and Injury Assessment after Mixed-field (Neutron and Gamma) Radiation in the Mouse Total-body Irradiation Model.

The risk of potential radiation exposure scenarios that include detonation of nuclear weapons, terrorist attacks on nuclear reactors, and the use of conventional explosives to disperse radioactive substances has increased in recent years. The majority of radiation biodosimetry and countermeasure studies have been performed using photon radiation even though many exposure scenarios predict mixed-field (neutron and photon) radiation. Hence, there is a need to evaluate biomarkers and accurately determine exposure levels of mixed-field combinations of neutrons and photons for an individual. These biomarkers will be critical for biodosimetry triage, treatment, and follow-up visits with such individuals. We evaluated the utility of multiple blood biomarkers for early response assessment of radiation exposure using a mouse (B6D2F1, males and females) total-body irradiation model exposed to a mixed-field (neutrons and gamma rays) using the Armed Forces Radiobiology Research Institute's Mark F nuclear research reactor. Total-body irradiation was given as a single exposure over a dose range from 1.5 to 6 Gy, dose rates of 0.6 and 1.9 Gy min, and different proportions of neutrons and gammas: either (67% neutrons + 33% gammas) or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total-body irradiation. Radiation-responsive protein biomarkers were measured using the Meso Scale Diagnostics' high-throughput MULTI-ARRAY plate-format platform (QuickPlex 120 Imager) and enzyme-linked immunosorbent assay kits. Results demonstrate (1) dose- and time-dependent changes in fms-related tyrosine kinase 3 ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte and granulocyte-macrophage colony-stimulating factors, thrombopoietin, erythropoietin, acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27, and procalcitonin; (2) dose- and time-dependent changes in blood cell counts (lymphocytes, neutrophils, platelets, red blood cells, and ratio of neutrophils to lymphocytes); (3) levels of IL-18, granulocyte and granulocyte-macrophage colony-stimulating factors, serum amyloid A, and procalcitonin were significantly higher in animals irradiated with 67% neutrons + 33% gammas compared to those irradiated with 30% neutrons + 70% gammas (p < 0.015), while no significant differences (p > 0.114) were observed in hematological biomarker counts; (4) exposure with 3-fold difference in dose rate (0.6 or 1.9 Gy min) revealed no significant differences in hematological and protein biomarker levels (p > 0.154); and (5) no significant differences in hematological and protein biomarker levels were observed in the sex-comparison study for any radiation dose at any time after exposure (p > 0.088). Results show that the dynamic changes in the levels of selected hematopoietic cytokines, organ-specific biomarkers, and acute-phase protein biomarkers reflect the time course and severity of acute radiation syndrome and may function as prognostic indicators of acute radiation syndrome outcome. These studies supplement an ongoing effort to deliver U.S. Federal Drug Administration-approved biodosimetry capabilities, which assess mixed-field radiation exposure.

A model combining age, equivalent uniform dose and IL-8 may predict radiation esophagitis in patients with non-small cell lung cancer.

BACKGROUND AND PURPOSE: To study whether cytokine markers may improve predictive accuracy of radiation esophagitis (RE) in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 129 patients with stage I-III NSCLC treated with radiotherapy (RT) from prospective studies were included. Thirty inflammatory cytokines were measured in platelet-poor plasma samples. Logistic regression was performed to evaluate the risk factors of RE. Stepwise Akaike information criterion (AIC) and likelihood ratio test were used to assess model predictions. RESULTS: Forty-nine of 129 patients (38.0%) developed grade ≥2 RE. Univariate analysis showed that age, stage, concurrent chemotherapy, and eight dosimetric parameters were significantly associated with grade ≥2 RE (p < 0.05). IL-4, IL-5, IL-8, IL-13, IL-15, IL-1α, TGFα and eotaxin were also associated with grade ≥2 RE (p < 0.1). Age, esophagus generalized equivalent uniform dose (EUD), and baseline IL-8 were independently associated grade ≥2 RE. The combination of these three factors had significantly higher predictive power than any single factor alone. Addition of IL-8 to toxicity model significantly improves RE predictive accuracy (p = 0.019). CONCLUSIONS: Combining baseline level of IL-8, age and esophagus EUD may predict RE more accurately. Refinement of this model with larger sample sizes and validation from multicenter database are warranted.

Comparison of Biodosimetry Biomarkers for Radiation Dose and Injury Assessment After Mixed-Field (Neutron and Gamma) and Pure Gamma Radiation in the Mouse Total-Body Irradiation Model.

The detonation of a nuclear weapon and the occurrence of a nuclear accident represent possible mass-casualty events with significant exposure to mixed neutron and gamma radiation fields in the first few minutes after the event with the ensuing fallout, extending for miles from the epicenter, that would result primarily in photon (gamma- and/or x-ray) exposure. Circulating biomarkers represent a crucial source of information in a mass-casualty radiation exposure triage scenario. We evaluated multiple blood biodosimetry and organ-specific biomarkers for early-response assessment of radiation exposure using a mouse (B6D2F1, males and females) total-body irradiation model exposed to Co gamma rays over a broad dose range (3-12 Gy) and dose rates of either 0.6 or 1.9 Gy min and compared the results with those obtained after exposure of mice to a mixed field (neutrons and gamma rays) using the Armed Forces Radiobiology Research Institute Co gamma-ray source and TRIGA Mark F nuclear research reactor. The mixed-field studies were performed previously over a broad dose range (1.5-6 Gy), with dose rates of either 0.6 or 1.9 Gy min, and using different proportions of neutrons and gammas: either (67% neutrons + 33% gammas) or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total-body irradiation. Results from Co gamma-ray studies demonstrate: (1) significant dose- and time-dependent reductions in circulating mature hematopoietic cells; (2) dose- and time-dependent changes in fms-related tyrosine kinase 3 ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte colony-stimulating factors, thrombopoietin, erythropoietin, acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27, procalcitonin but not in intestinal fatty acid binding protein; (3) no significant differences were observed between dose-rate groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-5, IL-12, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, CD27, CD45, and ratio of CD45 to CD27) for any radiation dose at any time after exposure (p > 0.148); (4) no significant differences were observed between sex groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, serum amyloid A, CD45) for any radiation dose at any time after exposure (p > 0.114); and (5) PCT level significantly increased (p < 0.008) in mice irradiated with 12 Gy on day 7 post-total-body irradiation without significant differences between groups irradiated at dose rates of either 0.6 or 1.9 Gy min (p > 0.287). Radiation-quality comparison results demonstrate that: (1) equivalent doses of pure gamma rays and mixed-field radiation do not produce equivalent biological effects, and hematopoietic syndrome occurs at lower doses of mixed-field radiation; (2) ratios of hematological and protein biomarker means in the Co study compared to mixed-field studies using 2× Co doses vs. 1× TRIGA radiation doses (i.e., 3 Gy Co vs. 1.5 Gy TRIGA) ranged from roughly 0.2 to as high as 26.5 but 57% of all ratios fell within 0.7 and 1.3; and (3) in general, biomarker results are in agreement with the relative biological effectiveness = 1.95 (Dn/Dt = 0.67) reported earlier by Armed Forces Radiobiology Research Institute scientists in mouse survival countermeasure studies.

Prediction of Radiation Esophagitis in Non-Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels.

Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non-small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy.

BACKGROUND/PURPOSE: Radiation treatment (RT) stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA) to analyze cytokines in non-small cell lung cancer (NSCLC) patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT) and conventionally fractionated RT (CFRT) without or with chemotherapy. METHODS: The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16), CFRT (n = 18), or CFRT (n = 107) with concurrent chemotherapy (ChRT). Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point. RESULTS: Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l. CONCLUSIONS: PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.

Radiation-induced lung toxicity in non-small-cell lung cancer: Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship.

BACKGROUND AND PURPOSE: Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. MATERIALS AND METHODS: Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. RESULTS: In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were -28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to -27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. CONCLUSIONS: Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.

Plasma Levels of IL-8 and TGF-ß1 Predict Radiation-Induced Lung Toxicity in Non-Small Cell Lung Cancer: A Validation Study.

PURPOSE AND OBJECTIVES: We previously reported that the combination of mean lung dose (MLD) and inflammatory cytokines interleukin-8 (IL-8) and transforming growth factor-ß1 (TGF-ß1) may provide a more accurate model for radiation-induced lung toxicity (RILT) prediction in 58 patients with non-small cell lung cancer (NSCLC). This study is to validate the previous findings with new patients and to explore new models with more cytokines. METHODS AND MATERIALS: One hundred forty-two patients with stage I-III NSCLC treated with definitive radiation therapy (RT) from prospective studies were included. Sixty-five new patients were used to validate previous findings, and all 142 patients were used to explore new models. Thirty inflammatory cytokines were measured in plasma samples before RT and 2 weeks and 4 weeks during RT (pre, 2w, 4w). Grade ≥2 RILT was defined as grade 2, and higher radiation pneumonitis or symptomatic pulmonary fibrosis was the primary endpoint. Logistic regression was performed to evaluate the risk factors of RILT. The area under the curve (AUC) for the receiver operating characteristic curves was used for model assessment. RESULTS: Sixteen of 65 patients (24.6%) experienced RILT2. Lower pre IL-8 and higher TGF-ß1 2w/pre ratio were associated with higher risk of RILT2. The AUC increased to 0.73 by combining MLD, pre IL-8, and TGF-ß1 2w/pre ratio compared with 0.61 by MLD alone to predict RILT. In all 142 patients, 29 patients (20.4%) experienced grade ≥2 RILT. Among the 30 cytokines measured, only IL-8 and TGF-ß1 were significantly associated with the risk of RILT2. MLD, pre IL-8 level, and TGF-ß1 2w/pre ratio were included in the final predictive model. The AUC increased to 0.76 by combining MLD, pre IL-8, and TGF-ß1 2w/pre ratio compared with 0.62 by MLD alone. CONCLUSIONS: We validated that a combination of mean lung dose, pre IL-8 level, and TGF-ß1 2w/pre ratio provided a more accurate model to predict the risk of RILT2 compared with MLD alone.

Metabolic response assessment with 18F-FDG PET/CT: inter-method comparison and prognostic significance for patients with non-small cell lung cancer.

OBJECTIVE: This study aimed to (1) compare the agreement of two evaluation methods of metabolic response in patients with non-small cell lung cancer (NSCLC) and determine their prognostic value and (2) explore an optimal cutoff of metabolic reduction to distinguish a more favorable subset of responders. METHODS: This is a secondary analysis of prospective studies. Enrolled patients underwent 18F-PET/CT within 2 weeks before, during, and months after radiotherapy (post-RT). Metabolic response was assessed using both Peter MacCallum (PM) method of qualitative visual assessment and University of Michigan (UM) method of semiquantitative measurement. The agreement between two methods determined response, and their prediction of outcome was analyzed. RESULTS: Forty-four patients with median follow-up of 25.2 months were analyzed. A moderate agreement was observed between PM- and UM-based response assessment (Kappa coefficient = 0.434), unveiling a significant difference in CMR rate (p = 0.001). Categorical responses derived from either method were significantly predictive of overall survival (OS) and progression-free survival (PFS) (p < 0.0001). Numerical percentage decrease of FDG uptake also showed significant correlations with survival, presenting a hazard ratio of 0.97 for both OS and PFS. A 75 % of SUV decrease was found to be the optimal cutoff to predict OS and 2-year progression. CONCLUSIONS: There was a modest discrepancy in metabolic response rates between PM and UM criteria, though both could offer predictive classification for survival. The percentage decrease provides an ordinal value that correlates with prolonged survival, recommending 75 % as the optimal threshold at identifying better responders.

Timing and intensity of changes in FDG uptake with symptomatic esophagitis during radiotherapy or chemo-radiotherapy.

PURPOSE: To study whether esophageal FDG activity changes by time of mid-course of fractionated radiotherapy (RT), and whether these changes are associated with radiation esophagitis in patients with non-small cell lung cancer (NSCLC). METHODS: Fifty patients with stage I-III NSCLC were enrolled prospectively and, all received ≥60 Gy RT. FDG-PET/CT scans were acquired prior to, and during-RT after delivery of 45 Gy. Normalized standardized uptake values (NSUV), defined by the esophageal maximum SUV relative to intravascular background level in the aortic arch, were sampled in the esophagus at the level of the primary tumor, sternal notch, aortic arch, carina, and gastro-esophageal junction. Symptomatic radiation esophagitis was defined as an event. RESULTS: Compared to baseline, esophageal NSUV increased significantly during-RT at the level of the primary tumor (1.09 ± 0.05 vs.1.28 ± 0.06, p = 0.001), but did not change at other levels in the esophagus. 16 patients had radiation esophagitis events and these patients had significantly higher during-RT to baseline NSUV ratios than those without esophagitis (1.46 ± 0.12, 95% CI 1.20-1.71; vs. 1.11 ± 0.05, 95% CI 1.01-1.21, p = 0.002). Maximum esophageal dose (p = 0.029), concurrent chemotherapy (p = 0.022) and esophageal FDG PET NSUV ratio (during-RT to baseline, p = 0.007), were independent factors associated with esophagitis and area under curves (AUC) were 0.76, 0.70 and 0.78, respectively. Combining esophageal maximum dose and FDG PET NSUV Ratio at the tumor level increased AUC to 0.85 (p = 0.016). CONCLUSION: FDG uptake increased in esophagus during-RT and this increase may predict radiation esphagitis during later course of treatment.

Impact of pedicle screw fixation on loss of deformity correction in patients with adolescent idiopathic scoliosis.

BACKGROUND: Loss of coronal correction has been reported in the presence of a solid posterior fusion mass in patients who are skeletally immature. Significant increases in postoperative coronal curvature are typically attributed to the presence of pseudarthrosis, loss of instrumentation fixation, or adding-on. We evaluated the clinical and radiographic factors associated with a loss of correction that was not attributed to these etiologies as well as the impact of pedicle screw fixation on loss of correction. METHODS: A prospective, longitudinal study database was retrospectively queried for patients with at least 2 years of follow-up who underwent surgery for adolescent idiopathic scoliosis. Loss of correction was defined (1) clinically, as a >5 degree increase in the inclinometer reading at any time interval after surgery, excluding preoperative values; or (2) radiographically, as an increase of ≥ 10 degrees in the coronal Cobb angle of an instrumented curve. Patients with pseudarthrosis, adding-on, or loss of fixation were excluded. RESULTS: Ninety-three of 800 patients (11.6%) had loss of deformity correction. Twenty-one patients (2.5%) had >5 degrees of inclinometer change and 76 patients (9.5%) had ≥10 degrees of Cobb change, with a mean loss of 10.85±4.2 degrees. When comparing pedicle screw constructs only, 10% of patients developed loss of correction as opposed to 20% of the patients with hybrid constructs (P=0.036). Factors associated with loss of correction were: age, hybrid construct, magnitude of thoracic curve, thoracic apical translation, and T1 tilt angle. CONCLUSION: This study reports a high percentage of loss of coronal correction (12%) after 2 years of follow-up that was not associated with infection, adding-on, or apparent pseudarthrosis. Larger magnitude thoracic curves with apical deviation and hybrid constructs were associated with an increased likelihood of loss of curve correction where use of pedicle screw fixation seems to decrease its incidence. LEVEL OF EVIDENCE: III.

Poor baseline pulmonary function may not increase the risk of radiation-induced lung toxicity.

PURPOSE: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). METHODS AND MATERIALS: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. RESULTS: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). CONCLUSIONS: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.

Impact of direct vertebral body derotation on rib prominence: are preoperative factors predictive of changes in rib prominence?

STUDY DESIGN: Multicenter retrospective review of prospectively collected data. OBJECTIVE: To determine the extent of rib deformity correction that can be expected with direct vertebral body derotation (DVBD) and investigate factors that may correlate with improved rib deformity correction. SUMMARY OF BACKGROUND DATA: DVBD is a powerful tool in the surgical correction of axial rotation in adolescent idiopathic scoliosis. The application of DVBD has decreased the use of thoracoplasty for cosmetic rib deformity correction, but the outcomes of DVBD without adjuvant thoracoplasty have not been well defined. METHODS: A multicenter database was retrospectively queried to identify patients with adolescent idiopathic scoliosis who underwent posterior spinal fusion with at least 2 years of follow-up and Lenke type 1 to 3 curves. All patients had undergone DVBD maneuvers during their surgery, and patients having undergone concurrent thoracoplasty were excluded from the study. The absolute change and percentage change from preoperative inclinometer readings were correlated with preoperative clinical and radiographic data. RESULTS: A total of 148 patients fulfilled the inclusion criteria. The mean age was 14.7 ± 2.1 years with a mean primary thoracic curve of 55.3° ± 9.3°. The mean preoperative inclinometer reading was 14.8° ± 4.5°, which reduced to 7.5° ± 4.0° postoperatively. Patients had a mean improvement of 54% ± 29% in rib prominence using DVBD. We attempted to correlate 23 of the most commonly used preoperative clinical, radiographic, and operative measures with postoperative inclinometer improvement. Interestingly, none correlated with rib deformity correction, including preoperative rib deformity (P = 0.16), thoracic curve flexibility (P = 0.71), presence of osteotomies (P = 0.60), and thoracic curve magnitude (P = 0.78). CONCLUSION: Utilizing DVBD, the surgeon can expect approximately 50% reduction in the rib deformity as assessed by inclinometer. This is irrespective of preoperative inclinometer measures, thoracic curve flexibility, and vertebral body rotation on standing and bending radiographs.

Automated renal stone volume measurement by noncontrast computerized tomography is more reproducible than manual linear size measurement.

PURPOSE: We compared the reproducibility of automated volume and manual linear measurements using same study supine and prone, low dose, noncontrast computerized tomography series. MATERIALS AND METHODS: The patient cohort comprised 50 consecutive adults with a mean age of 56.4 years in whom renal calculi were identified during computerized tomography colonography screening. The largest stone per patient was assessed with the supine and prone computerized tomography series serving as mutual controls. Automated stone volume was derived using a commercially available coronary artery calcium scoring tool. Supine-prone reproducibility for automated volume was compared with intra-observer supine-prone manual linear measurement. Interobserver variability was also assessed for manual linear measurements of the same supine or prone series. RESULTS: Mean ± SD linear size and volume of the 50 index calculi was 4.5 ± 2.7 mm (range 1.8 to 16) and 141.7 ± 456.1 mm(3), respectively. The mean supine-prone error for automated stone volume was 16.3% compared with an average 11.7% 1-dimensional intra-observer error for manual axial measurement. Only 2 of 15 cases with a volume error of greater than 20% were 5 mm or greater in linear size. The average interobserver linear error for the same computerized tomography series was 26.3% but automated volume measurement of the same series did not vary. CONCLUSIONS: Automated noncontrast computerized tomography renal stone volume is more reproducible than manual linear size measurement and it avoids the often large interobserver variability seen with manual assessment. Since small linear differences correspond to much larger volume changes, greater absolute volume errors are acceptable. Automated volume measurement may be an improved clinical parameter to use for following the renal stone burden.

Arthroscopic validation of radiographic grading scales of osteoarthritis of the tibiofemoral joint.

OBJECTIVE: The purpose of this study was to use the Kellgren-Lawrence, Ahlback, and Brandt grading scales to correlate radiographic grade of osteoarthritis with the actual degree of articular cartilage degeneration within the tibiofemoral joint in patients with chronic knee pain. SUBJECTS AND METHODS: The study group consisted of 125 patients with symptomatic osteoarthritis of the tibiofemoral joint. For all patients, standing anteroposterior radiographs of the knee were obtained before arthroscopic knee surgery. Each articular surface of the tibiofemoral joint was graded at arthroscopy. Two radiologists retrospectively reviewed the knee radiographs without knowledge of the arthroscopic findings to determine the presence and severity of osteoarthritis of the tibiofemoral joint using the Kellgren-Lawrence, Ahlback, and Brandt grading scales. Correlation coefficients describing the relation between grade of osteoarthritis and severity of articular cartilage degeneration were calculated for each grading scale. RESULTS: The correlation coefficients for the Kellgren-Lawrence, Ahlback, and Brandt grading scales were 0.49, 0.41, and 0.56, respectively. The differences between the correlation coefficients for the Kellgren-Lawrence and Ahlback grading scales and the correlation coefficients for the Brandt and Ahlback grading scales were statistically significant (p < 0.05). Many patients with no radiographic findings of osteoarthritis had significant articular cartilage degeneration within the tibiofemoral joint. CONCLUSION: The Kellgren-Lawrence and Brandt grading scales were equally effective in defining the presence of and estimating the severity of osteoarthritis of the tibiofemoral joint but had only a moderately strong correlation with the actual degree of articular cartilage degeneration.

Correlation between radiographic findings of osteoarthritis and arthroscopic findings of articular cartilage degeneration within the patellofemoral joint.

OBJECTIVES: To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain. SUBJECTS AND METHODS: The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined. RESULTS: The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively. CONCLUSION: Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

Radiographic findings of osteoarthritis versus arthroscopic findings of articular cartilage degeneration in the tibiofemoral joint.

PURPOSE: To retrospectively correlate radiographic findings of osteoarthritis of the tibiofemoral joint with arthroscopic findings of articular cartilage degeneration within the tibiofemoral joint in patients with chronic knee pain. MATERIALS AND METHODS: The study was performed in compliance with HIPAA regulations. Approval from an institutional review board and a waiver of informed consent were obtained. The study group consisted of 125 patients with osteoarthritis of the tibiofemoral joint (66 men, 59 women; age range, 35-77 years; average age, 52 years) and 25 patients of similar age (14 men, 11 women; age range, 36-69 years; average age, 50 years) with no osteoarthritis of the tibiofemoral joint. All patients underwent standing anteroposterior radiography of the knee prior to arthroscopic knee surgery. Each articular surface of the tibiofemoral joint was graded at arthroscopy. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the medial and lateral compartments of the tibiofemoral joint were determined. RESULTS: The sensitivity of marginal osteophytes, joint space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration was 67%, 46%, 16%, and 10%, respectively, for the medial compartment and 49%, 7%, 6%, and 3%, respectively, for the lateral compartment. The specificity of marginal osteophytes, joint space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration was 73%, 95%, 100%, and 100%, respectively, for the medial compartment and 81%, 100%, 100%, and 100%, respectively, for the lateral compartment. CONCLUSION: Marginal osteophytes were the most sensitive radiographic feature for the detection of osteoarthritis of the tibiofemoral joint. Joint space narrowing, subchondral sclerosis, and subchondral cysts were less sensitive radiographic features of osteoarthritis and rarely occurred in the absence of associated osteophyte formation.

Subchondral bone marrow edema in patients with degeneration of the articular cartilage of the knee joint.

PURPOSE: To retrospectively determine at magnetic resonance (MR) imaging the prevalence of subchondral bone marrow edema beneath arthroscopically proved articular cartilage defects. MATERIALS AND METHODS: The study was performed in compliance with HIPAA regulations, and a waiver of informed consent was obtained from the institutional review board before the study was performed. The study consisted of 132 patients (70 men, 62 women; average age, 53 years) with articular cartilage defects of the knee joint who underwent MR imaging of the knee and subsequent arthroscopic knee surgery. At the time of arthroscopy, each articular cartilage lesion was graded by using the Noyes classification system. MR examinations were retrospectively reviewed to determine the size, depth, and location of subchondral bone marrow edema without knowledge of the arthroscopic findings. Pairwise Fisher exact tests and two-sample t tests were used to correlate MR imaging findings of subchondral bone marrow edema with the arthroscopic grade of articular cartilage degeneration. RESULTS: Subchondral bone marrow edema was seen beneath 105 (19%) of 554 articular cartilage defects identified at arthroscopy. It was not observed beneath any of the six grade 1 cartilage defects but was observed beneath eight (4.9%) of 163 grade 2A defects, 40 (14.4%) of 278 grade 2B defects, 54 (55.1%) of 98 grade 3A defects, and three (33.3%) of nine grade 3B defects. Subchondral bone marrow edema was also seen beneath four (1.4%) of 238 articular surfaces that appeared normal at arthroscopy. The mean depth and cross-sectional area of subchondral bone marrow edema increased with increasing grade of the articular cartilage lesion. CONCLUSION: Higher grades of articular cartilage defects are associated with higher prevalence and greater depth and cross-sectional area of subchondral bone marrow edema.

Good management. Make boards work better.

Performance reviews for trust boards are rare, despite their strategic importance. Cohesion between executives and non-executives, and willingness for board members to challenge one another, are critical. Too much challenge and too little trust can suppress innovation.