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Biomedical subjects

Elkan F Halpern

Publications and source records attributed to Elkan F Halpern.

At least 37 records · Page 2Linked to original sources

Attenuation of acute and chronic pulmonary emboli.

PURPOSE: To compare retrospectively the attenuation coefficients of acute and chronic pulmonary embolism (PE). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. The study was compliant with requirements of the Health Insurance Portability and Accountability Act. All patients with chronic PE, from July 2001 to January 2004, were identified via a radiology report search system; of the 39 identified, 25 were excluded because the thrombi were too small to measure or were obscured by streak artifacts or because there was no corroborative evidence of chronic PE. Of 27 consecutive patients with acute PE who were also identified, two were excluded because of streak artifacts. The final study group included six women and eight men with chronic PE (mean age, 50 years; range, 26-76 years) and 11 women and 14 men with acute PE (mean age, 61 years; range, 33-83 years) (P = .01 for age). Images were acquired with a four-detector row computed tomographic scanner and 1.25-mm collimation. Two readers made independent attenuation measurements of the largest thrombus in each patient at a workstation. Statistical analysis included calculation of means and standard deviations, the t test, and the Bland-Altman test. RESULTS: Reader 1 found mean attenuation of 90 HU +/- 30 (range, 54-155 HU) for chronic PE and 33 HU +/- 15 (range, 6-63 HU) for acute PE (P < .001). Reader 2 found mean attenuation measurements of 83 HU +/- 32 (range, 32-135 HU) for chronic PE and 33 HU +/- 14 (range, 13-65 HU) for acute PE (P < .001). The mean attenuation for both readers was 33 HU for acute PE (95% confidence interval: 26, 41 HU) and 87 HU for chronic PE (95% confidence interval: 66, 107 HU). The Bland-Altman test demonstrated agreement between readers. CONCLUSION: The mean attenuation measurement in chronic PE is significantly higher than in acute PE.

Acute Disease↗

Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy.

Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (>70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy.

Humans↗

Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain.

PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton ((1)H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution (1)H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.

Animals↗

In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography.

BACKGROUND: The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution ( approximately 10 microm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. METHODS AND RESULTS: Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non-ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying > or =2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively (P=0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 microm, respectively (P=0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness < or =65 microm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group (P=0.012). No procedure-related complications occurred. CONCLUSIONS: OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.

Aged↗

Detection of urinary tract stones at low-radiation-dose CT with z-axis automatic tube current modulation: phantom and clinical studies.

PURPOSE: To evaluate depiction of urinary tract calculi at computed tomography (CT) with a z-axis modulation technique at various noise indexes to reduce radiation dose and preserve image quality. MATERIALS AND METHODS: Sixteen radiopaque kidney stones (2.5-19.2 mm in diameter) were embedded in the collecting systems of two bovine kidneys immersed in a water bath. A kidney phantom was made by placing the kidneys in an elliptical Plexiglas phantom (32 x 20 x 20 cm) filled with physiologic saline. The phantom was scanned at 16-detector row CT with a fixed tube current (300 mA) and z-axis modulation at noise indexes of 14, 20, 25, 35, and 50; remaining imaging parameters were held constant. Two abdominal radiologists reviewed images from most to least noisy. Images were evaluated for presence of stones and size, site, and attenuation value of each stone. Readers also graded conspicuity and margins of each stone on a five-point scale. In addition, follow-up studies of 22 patients (mean age, 46 years; range, 26-57 years; male-female ratio, 14:8) with kidney and ureteral stones who underwent CT with z-axis modulation (noise index, 14 and 20) were evaluated in the same manner. Statistical analysis was performed with the Student t test, Wilcoxon signed rank test, and kappa test of interobserver agreement. Institutional review board approval was obtained, and informed consent was not needed. RESULTS: In the phantom study, all 16 stones were identified on images obtained with a fixed tube current and z-axis modulation at noise indexes of 14, 20, and 25 (with a reduction in radiation dose of up to 77% compared with that of fixed tube current scanning). Three stones (<5 mm) were not visualized with z-axis modulation at noise indexes of 35 and 50. No significant difference was shown for conspicuity of kidney stones in 22 patients who underwent CT with z-axis modulation (with a 43%-66% reduction in radiation dose) when compared with results of previous fixed tube current studies (P > .05). CONCLUSION: Kidney stones (< or =2.5 mm) can be adequately depicted with the z-axis modulation technique, with a 56%-77% reduction in radiation dose. In patients with urinary tract stones, the technique results in a 43%-66% reduction in radiation dose at noise indexes of 14 and 20 without compromising stone depiction.

Adult↗

Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model.

PURPOSE: To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model. MATERIALS AND METHODS: With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation]) was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42 tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C for 5 minutes) alone, (b) RF ablation followed by radiation therapy with a total dose of 20 Gy, (c) 20-Gy radiation alone, and (d) no treatment. Another 19 tumors were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed by 5-Gy radiation, (f) 5-Gy radiation alone, or (g) no treatment. Animals were followed up until survival end point (either until tumor growth to 30 mm in diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall). Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was performed in 15 additional tumors at survival end point and 18 other representative tumors at other specified end points. RESULTS: Combined RF ablation and 20-Gy radiation resulted in complete local control in nine (82%) of 11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local control was achieved in rats with radiation therapy alone or in controls. Median end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end-point survival was 13 days +/- 5 (standard deviation) for the control group, 34 days +/- 31 with RF ablation alone, and 43 days +/- 16 with 20-Gy radiation alone. Mean survival was significantly greater with 20-Gy radiation and RF ablation combined: 94 days +/- 34 (P < .001 compared with all other groups). Mean survival for rats that received 5-Gy radiation with RF ablation versus without was 46 days +/- 37 versus 24 days +/- 11, respectively. CONCLUSION: Combined RF ablation and external-beam radiation therapy increased animal survival compared with that with either of the treatments alone or with no treatment.

Animals↗

The effect of prior colonic imaging on endoscopic productivity: potential impact of computed tomographic colonography.

BACKGROUND & AIMS: If computed tomographic colonography (CTC) is used for primary colorectal cancer (CRC) screening with a small polyp size threshold to define a CTC study as positive, a substantial portion of all colonoscopies performed annually will be to follow up positive CTC examinations. Moreover, the majority of positive CTC examinations would be false positives (FP). This case-control study was undertaken to test the hypothesis that colonoscopy examinations resulting from FP CTC studies would take longer to complete than negative screening colonoscopies. METHODS: Endoscopic records of a large, urban hospital were reviewed to identify all patients who had either a positive barium enema (BE) study or flexible sigmoidoscopy (FS) and a negative follow-up colonoscopy examination (these patients were used as surrogates for CTC FP cases). For each of the 28 FP patients or cases identified, 2 screening colonoscopies performed by the same endoscopist within the same time period were identified and used as matched controls. A two-way analysis of variance test was performed to assess for differences in time to complete colonoscopies between these 2 groups, controlling for the individual endoscopist. RESULTS: FP colonoscopies took an average of 24.0 minutes to complete, whereas negative screening colonoscopies took 14.9 minutes; FP colonoscopies required 61% more active time to complete. This highly statistically significant difference (P < .0001) persisted with subset analyses that only included BE or FS cases and when fellow or surgeon cases were excluded. CONCLUSIONS: FP colonoscopies take longer to perform than negative screening colonoscopies. If CTC is implemented as the primary modality for CRC screening, these FP examinations could comprise a substantial percentage of the colonoscopies performed, potentially leading to a significant decrease in endoscopic productivity.

Adult↗

Small incidental pulmonary nodules: how useful is short-term interval CT follow-up?

PURPOSE: To determine whether short-term (<6 month) follow-up imaging by thoracic CT is necessary to evaluate small (< or =4 mm) noncalcified nodules (NCN) in patients with no history of malignancy or acute lung disease. MATERIALS AND METHODS: We reviewed serial thoracic helical CT scans between 1999-2000 obtained for the evaluation or follow-up imaging of small NCNs. CT scans were performed at 5-mm collimation. Patients were excluded if they had a history of neoplasm, infection, pulmonary fibrosis, or immune deficiency; also excluded if nodule(s) > or =5 mm at intake, or no follow-up scan within 1 year. NCNs were evaluated for number, size, configuration, and change in size over time. Exact 95% Confidence Intervals were used to estimate chances of nodule growth in 3-, 6-, and 12- month intervals. RESULTS: A total of 1826 patients received a CT for NCNs. Four hundred fourteen patients met inclusion criteria (221 women, 193 men; mean age, 65.6 years). Eighty-five patients had a single NCN, 329 had multiple NCNs. One hundred seventy-three patients had additional > or =5 mm nodules. One hundred twenty-seven patients were lost to follow up within the 1-year period. Eight nodules cleared. None of the < or =4 mm NCNs grew on follow-up imaging within 12 months. Three patients developed lung cancer in other nodules > or =5 mm (5-10 mm). These nodules grew on follow up intervals of 3-13 months. One patient had a 19 mm benign hamartoma that grew in 9 months. The calculated chance that a NCN < or =4 mm will grow within 3, 6, and 12 months (95% CI) is < or =0.89%, 1.01%, and 1.28%, respectively. CONCLUSION: The chance of growth in < or =4 mm NCNs in a 3- to 6-month period in patients with no previous history of malignancy or immune disorder is small; therefore, short-term follow-up imaging (<12 month) for nodules < or =4 mm is not necessary.

Adult↗

Hormone replacement therapy in postmenopausal women: breast tissue perfusion determined with MR imaging--initial observations.

PURPOSE: To use magnetic resonance (MR) imaging to evaluate tissue perfusion in the normal breast parenchyma of postmenopausal women with current or recent hormone replacement therapy (HRT). MATERIALS AND METHODS: The study was approved by the institutional subcommittee on human studies, and informed consent was obtained from all patients prior to MR imaging. Sixty postmenopausal women (age range, 44-77 years) were grouped according to HRT received: estrogen replacement therapy (ERT) (n = 13), combined (estrogen and progesterone) replacement therapy (CRT) (n = 16), selective estrogen receptor modulator (SERM) therapy (n = 8), and no (hormone replacement) therapy (NT) (n = 23). MR imaging with a 1.5-T magnet was performed by using gradient-echo and dynamic contrast material-enhanced echo-planar pulse sequences before and after gadopentetate dimeglumine injection. Precontrast T1 relaxation times were measured, after which extraction-flow product (EFP) maps were calculated with a multicompartmental model. Analysis of variance was performed. RESULTS: Age did not significantly differ between the groups (P > .3). Women receiving ERT or CRT at the time of MR imaging had higher EFP values (7.3 mL . 100 g(-1) . min(-1)+/- 2.6 and 7.1 mL . 100 g(-1) . min(-1)+/- 3.8, respectively) than did women receiving NT (4.4 mL . 100 g(-1) . min(-1)+/- 2.1) (P = .012 and P = .008, respectively) or SERM therapy (3.9 mL . 100 g(-1) . min(-1)+/- 1.1) (P = .015 and P = .013, respectively). Women who ended ERT or CRT 1-47 months before MR examination had lower EFP values than did women with current ERT or CRT and had higher EFP values than did women receiving NT or SERM therapy (6.2 mL . 100 g(-1) . min(-1)+/- 2.4 and 5.9 mL . 100 g(-1) . min(-1)+/- 3.8, respectively), but the observed differences were not significant (P > .1). Differences in T1 between all groups were not significant (P > .5). CONCLUSION: Higher breast tissue perfusion is observed in postmenopausal women receiving HRT.

Adult↗

Intramyocellular lipid quantification: repeatability with 1H MR spectroscopy.

PURPOSE: To prospectively determine the repeatability and variability of tibialis anterior intramyocellular lipid (IMCL) quantifications performed by using 1.5-T hydrogen 1 (1H) magnetic resonance (MR) spectroscopy in healthy subjects. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. The authors examined the anterior tibial muscles of 27 healthy subjects aged 19-48 years (12 men, 15 women; mean age, 25 years) by using single-voxel short-echo-time point-resolved 1H MR spectroscopy. During a first visit, the subjects underwent 1H MR spectroscopy before and after being repositioned in the magnet bore, with voxels carefully placed on the basis of osseous landmarks. Measurements were repeated after a mean interval of 12 days. All spectra were fitted by using Java-based MR user interface (jMRUI) and LCModel software, and lipid peaks were scaled to the unsuppressed water peak (at 4.7 ppm) and the total creatine peak (at approximately 3.0 ppm). A one-way random-effects variance components model was used to determine intraday and intervisit coefficients of variation (CVs). A power analysis was performed to determine the detectable percentage change in lipid measurements for two subject sample sizes. RESULTS: Measurements of the IMCL methylene protons peak at a resonance of 1.3 ppm scaled to the unsuppressed water peak (IMCL(W)) that were obtained by using jMRUI software yielded the lowest CVs overall (intraday and intervisit CVs, 13.4% and 14.4%, respectively). The random-effects variance components model revealed that nonbiologic factors (equipment and repositioning) accounted for 50% of the total variability in IMCL quantifications. Power analysis for a sample size of 20 subjects revealed that changes in IMCL(W) of greater than 15% could be confidently detected between 1H MR spectroscopic measurements obtained on different days. CONCLUSION: 1H MR spectroscopy is feasible for repeatable quantification of IMCL concentrations in longitudinal studies of muscle metabolism.

Adult↗

Chest CT performed with z-axis modulation: scanning protocol and radiation dose.

Institutional review board approval of the study protocol and waiver of informed consent were obtained. This study was compliant with the Health Insurance Portability and Accountability Act. The purpose of this study was to retrospectively assess the scanning protocol and radiation dose associated with z-axis automatic tube current modulation in multi-detector row CT scanning of the chest. Fifty-three patients (mean age, 54 years; age range, 26-77 years; 25 men, 28 women) underwent 16-detector row chest CT with z-axis modulation and noise indexes of 10.0, 12.5, and 15.0 HU. Two radiologists independently compared images acquired with z-axis modulation and fixed tube current (180-300 mA) techniques for image noise, diagnostic acceptability, and depiction of peripheral bronchovascular markings. Tube current-time product was calculated for each study. There was good interobserver agreement between the two readers (kappa = 0.72). Compared with the fixed tube current technique, z-axis modulation provides acceptable image noise for chest CT, with an 18% and 26% reduction in tube current-time product at 10.0- and 12.5-HU noise indexes, respectively.

Adult↗

Lipomatous hypertrophy of the interatrial septum: prevalence and features on fusion 18F fluorodeoxyglucose positron emission tomography/CT.

OBJECTIVE: To determine the prevalence of lipomatous hypertrophy of the interatrial septum (LHIS) on CT and its metabolic pattern on 18F fluorodeoxyglucose (FDG)-positron emission tomography (PET). METHOD AND MATERIALS: Eight hundred two CT PET scans were reviewed. Patients were included if the interatrial septum was > or = 1 cm and excluded if there was evidence of malignancy in the adjacent lung, hilum, or mediastinum. CT scans were fused with PET scans, and the mean standardized uptake value (SUV) was calculated over the LHIS, chest wall (CW) fat, and mediastinal blood pool. CT scans were reviewed for presence of excessive fat in the mediastinum, pericardial, peridiaphragmatic, peritoneal, and retroperitoneal regions and for the presence of emphysema. Medical records were reviewed for body mass index (BMI) and history of arrhythmia. RESULTS: Twenty-three of 802 patients (2.8%) had LHIS on CT (9 women and 14 men); average age was 75.6 years (range, 58 to 95 years). Average BMI of 17 patients (+/- SD) was 31 +/- 4.9 (range, 22.1 to 39.9). Mean CT values were as follows: thickening of LHIS, 1.47 +/- 0.35 cm (range, 1.07 to 2.25 cm); LHIS, - 79.6 + 24.5 Hounsfield unit (HU) [range, - 11 to - 121 HU]. LHIS was dumbbell shaped in 18 patients. Mean SUVs were as follows: LHIS, 1.84 +/- 0.10 (range, 0.48 to 3.48); CW fat, 0.36 + 0.37 (range, 0.04 to 1.98); blood pool, 1.74 + 0.51 (range, 0.25 to 2.71). The SUV of LHIS was greater than the SUV of CW wall fat in all patients (p < 0.0001). There was significant correlation between SUV and thickness of the LHIS on CT (p < 0.0001, r = 0.883). Those with dumbbell-shaped LHIS (p < 0.003) and presence of emphysema (p < 0.0377) had greater LHIS mean SUV. CONCLUSION: The SUV of LHIS was greater than the SUV of CW fat in all patients. LHIS with greater thickness or dumbbell shape had greater FDG uptake. These findings on CT and PET are important to recognize in order to avoid false-positive FDG-PET interpretations.

Aged↗

Automated computer-assisted categorization of radiology reports.

OBJECTIVE: The objective of our study was to create and validate an automated computerized method for the categorization of narrative text radiograph reports. MATERIALS AND METHODS: Using commercially available software with embedded Boolean logic, we created a text search algorithm to categorize reports of radiography examinations into "fracture,"normal," and "neither normal nor fracture." The algorithm was refined and optimized through repeated testing on 512 consecutive ankle radiography reports from a single clinical imaging center. The final algorithm was applied on a different set of 750 consecutive radiography reports of the spine and extremities produced at three different clinical imaging sites and interpreted by 44 different radiologists. Expert reviewers assessed the accuracy of the final classification. The chi-square test or Fisher's exact test was performed to determine the reproducibility of results across different clinical imaging sites. RESULTS: The computerized classification was highly accurate for the classification of radiography reports into "normal" (specificity, 91.6%; sensitivity, 91.3%), "neither normal nor fracture"(sensitivity, 87.8%; specificity, 94.9%), and "fracture"(sensitivity, 94.1%; specificity, 98.1%) categories. This performance showed no significant difference across the three sites (p >0.05). CONCLUSION: Computerized categorization of narrative-text radiography reports is highly sensitive and specific and can be used to classify reports from different imaging sites generated by different radiologists. This method can be an extremely powerful tool in future cost-effectiveness studies, health care policy studies, operations assessments, and quality control.

Algorithms↗

The status of appendiceal CT in an urban medical center 5 years after its introduction: experience with 753 patients.

OBJECTIVE: Appendiceal CT was introduced at our hospital in 1996 and now is used in most patients. The use of appendiceal CT has generated controversy and mixed results in various investigations. Our purpose was to determine the percentage of patients for whom CT was performed, incidence of appendicitis, accuracy of CT, percentage of equivocal interpretations, and negative appendectomy rates for those patients who did and did not undergo CT. MATERIALS AND METHODS: Patient records from 2001 that included clinical or CT preoperative examination were analyzed, with follow-up through 2003. Patient age and sex, clinical presentation, CT techniques, CT interpretations, operative reports, pathology reports, and patient disposition were determined. Final diagnoses were provided by pathologic criteria, patient follow-up, or patient survey. Statistical analysis included Fisher's exact test and receiver operating characteristic (ROC) curves. RESULTS: Of 753 patients, 663 (88%) were examined on CT for suspected appendicitis and 90 had an appendectomy without undergoing CT. The incidence of appendicitis in the patients who underwent CT was 39.2%. The sensitivity and specificity of CT were 99% and 95%, respectively; the area under the ROC curve was 0.9896; and the percentage of equivocal CT interpretations was 3.3%. The false-negative appendectomy rates were 3.0% and 5.6% for patients with and without CT, respectively (for all patients, p = 0.326; for female pediatric patients, p = 0.030). CONCLUSION: Five years ago, the negative appendectomy rate dropped from 20% to 7%, and it is now 3.0%. The incidence of appendicitis in patients who are examined on CT is stable compared with similar cohorts from prior investigations. Patients who do not undergo CT also have a low negative appendectomy rate, but this relatively small group is selected on the basis of a convincing clinical presentation. Female pediatric patients likely would have a lower negative appendectomy rate with greater use of CT.

Acute Disease↗

Application of recently developed computer algorithm for automatic classification of unstructured radiology reports: validation study.

PURPOSE: To validate the accuracy of Lexicon Mediated Entropy Reduction (LEXIMER), a new information theory-based computer algorithm developed by the authors for independent analysis and classification of unstructured radiology reports based on the presence of clinically important findings (F(T), where (T) represents "true") and recommendations for subsequent action (R(T)). MATERIALS AND METHODS: The study was approved by the Human Research Committee of the institutional review board. Consecutive de-identified radiology reports (n = 1059) comprising results of barium studies (n = 99), computed tomography (n = 107), mammography (n = 90), magnetic resonance imaging (n = 108), nuclear medicine (n = 99), positron emission tomography (n = 106), radiography (n = 212), ultrasonography (n = 131), and vascular procedures (n = 107) were independently analyzed by two radiologists and then with LEXIMER to categorize the reports into F(T) and F(T)0 (containing or not containing clinically important findings) categories and R(T) and R(T)0 (containing or not containing recommendations for subsequent action) categories. Accuracy, sensitivity, specificity, and positive and negative predictive values of LEXIMER for placing reports into F(T) and F(T)0 and R(T) and R(T)0 categories were assessed by using appropriate statistical tests. RESULTS: There was strong interobserver concordance between the two radiologists for placing radiology reports into F(T) and R(T) categories (kappa = 0.9, P < .01). For the LEXIMER program, accuracy, sensitivity, specificity, and positive and negative predictive values, respectively, were 97.5% (95% confidence interval [CI]: 96.6%, 98.5%), 98.9% (95% CI: 97.9%, 99.6%), 94.9% (95% CI: 93.1%, 96.0%), 97.5% (95% CI: 96.6%, 98.0%), and 97.7% (95% CI: 95.8%, 98.8%) for placing radiology reports into F(T) and F(T)0 categories and 99.6% (95% CI: 99.2%, 99.9%), 98.2% (95% CI: 95.0%, 99.6%), 99.9% (95% CI: 99.4%, 99.99%), 99.4% (95% CI: 96.3%, 99.9%), and 99.7% (95% CI: 98.9%, 99.9%) for placing reports into R(T) and R(T)0 categories. CONCLUSION: LEXIMER is an accurate automated engine for evaluating the percentage positivity of clinically important findings and rates of recommendation for subsequent action in unstructured radiology reports.

Algorithms↗

Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials.

CONTEXT: In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown. OBJECTIVE: To determine trends in the rates of treatment-related (toxic) death, objective response, and serious toxicity and to identify factors associated with these outcomes. DATA SOURCES: We searched abstracts and journal articles reporting the results of phase 1 cancer treatment trials originally submitted to annual meetings of the American Society of Clinical Oncology (ASCO) from 1991 through 2002. STUDY SELECTION: We focused on published single-agent trials that enrolled patients with advanced solid tumors and excluded studies testing agents already approved by the US Food and Drug Administration at the time of the ASCO presentation. DATA EXTRACTION: Multiple observers independently extracted information on trial design, location, sponsorship, types of tumors treated, drug class, route of administration, and clinical outcomes. DATA SYNTHESIS: The overall toxic death rate for 213 studies (involving 6474 cancer patients) published in peer-reviewed journals was 0.54%, while the overall objective response rate was 3.8%. Toxic death rates decreased over the study period, from 1.1% over the first 4 years of the study (1991-1994) to 0.06% over the most recent 4-year period (1999-2002) (P<.01). Response rates also decreased but by proportionally much less. After adjusting for characteristics of the experimental trials and the investigational agents, the odds of a patient dying from an experimental treatment while participating in a trial submitted during the most recent 4-year period were less than one tenth those of a patient participating in a trial submitted during the first 4-year period (odds ratio, 0.09; 95% confidence interval, 0.01-0.67; P = .009). In comparison, the adjusted odds of a patient experiencing an objective response over the same time periods decreased by approximately half (odds ratio, 0.46; 95% confidence interval, 0.32-0.66; P<.001). CONCLUSIONS: The level of risk experienced by cancer patients who participate in phase 1 treatment trials appears to have improved over the 12-year period from 1991 through 2002. Because toxic death rates have decreased more quickly than have objective response rates, the ratio of risk to benefit may have also improved. These changes relate in part to the targeted and less-toxic nature of newer cancer drugs and are coincident with the increased attention that has been paid to the safety of clinical research over the time period we analyzed.

Antineoplastic Agents↗

The age at which women begin mammographic screening.

BACKGROUND: The American Cancer Society recommends yearly mammographic screening for women starting at the age of 40 years. The authors examined the age at which women began screening at a large tertiary care center. METHODS: Utilization of mammography was assessed in a population of 72,417 women who received 254,818 screening mammograms at the Massachusetts General Hospital Avon Comprehensive Breast Center from January 1, 1985 to February 19, 2002, of which 940 received their first mammogram between January 16, 2000 and February 19, 2002. RESULTS: The median age at first mammogram for women in the population as a whole was 40.4 years. Sixty percent of women had their first mammogram by the end of their 40th year, and almost 90% had begun screening by age 50 years. However, these reassuring findings were not seen in several specific subpopulations of women. Black women began screening at a median age of 41.0 years, 0.7 years later than white women. Hispanic women began screening at a median age of 41.4 years, 1.1 years later than non-Hispanic women. Obese women began screening at a median age of 41.2 years, 1.6 years later than thin women. Women without a primary care physician began screening at a median age of 42.1 years, 1.8 years later than women with a primary care physician. Women without private health insurance began screening at a median age of 46.6 years, 6.3 years later than women with private health coverage. Women who did not speak English began screening at a median age of 49.3 years, 9.0 years later than women for whom English was the primary language. Women who both lacked private health insurance and spoke a language other than English began screening at a median age of 55.3 years, 15.2 years later than women without these characteristics. CONCLUSIONS: The analysis presented in the current study provided one of the most detailed descriptions of the age at screening initiation to be performed to date. Most women in the study population began screening by the end of their 40th year. This contrasted with the widespread failure of women to return promptly for subsequent annual examinations. However, specific subpopulations of women were at risk for not beginning screening on time, including women without private insurance, women without a primary care physician, and women who did not speak English. These findings suggest that there is little to be gained from populationwide efforts to encourage entry into the screening process, and that public health efforts should be focused on those subpopulations of women at highest risk for not using screening. These results also indicate that public health efforts to encourage women to start screening may be less critical than interventions to improve prompt return once they have entered the screening system.

Adult↗

Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease.

OBJECTIVES: This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome. BACKGROUND: The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo. METHODS: Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectoris, unstable angina pectoris,and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation. RESULTS: A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80). CONCLUSIONS: Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy.

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