Assessment of Bioprotect's Biodegradable Balloon System as a Rectal Spacer in Radiotherapy: An Animal Study on Tissue Response and Biocompatibility.

Prostate cancer is a significant health concern for men, emphasizing the need for effective treatment strategies. Dose-escalated external beam radiotherapy shows promise in improving outcomes but presents challenges due to radiation effects on nearby structures, such as the rectum. Innovative techniques, including rectal spacers, have emerged to mitigate these effects. This study comprehensively assessed tissue responses following the implantation of the Bioprotect biodegradable fillable balloon as a rectal spacer in a rat model. Evaluation occurred at multiple time points (4, 26, and 52 weeks) post-implantation. Results revealed localized tissue responses consistent with the expected reaction to biodegradable materials, characterized by mild to moderate fibrotic reactions and encapsulation, underscoring the safety and biocompatibility of the balloon. Importantly, no other adverse events occurred, and the animals remained healthy throughout the study. These findings support its potential clinical utility in radiotherapy treatments to enhance patient outcomes and minimize long-term implant-related complications, serving as a benchmark for future similar studies and offering valuable insights for researchers in the field. In conclusion, the findings from this study highlight the safety, biocompatibility, and potential clinical applicability of the Bioprotect biodegradable fillable balloon as a promising rectal spacer in mitigating radiation-induced complications during prostate cancer radiotherapy.

How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT.

Patients undergoing 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) whole-body oncologic positron emission tomography (PET)/computed tomography (CT) are studied while fasting. Cardiac FDG uptake in fasted patients has been widely reported as variable. It is important to understand the normal patterns of cardiac FDG activity that can be seen in oncologic FDG PET/CT studies. These include focal and regional patterns of increased FDG myocardial activity. Focal activity can be observed in papillary muscles, the atria, the base, and the distal anteroapical region of the left ventricle. Regional increased cardiac FDG activity may be diffuse or localized in the posterolateral wall or the base of the left ventricle. Abnormal patterns of cardiac FDG activity not related to malignancy include those associated with lipomatous hypertrophy of the interatrial septum, epicardial and pericardial fat, increased atrial activity associated with atrial fibrillation or a prominent crista terminalis, cardiac sarcoidosis, endocarditis, myocarditis, and pericarditis. Knowledge of these patterns of cardiac FDG activity is important to be able to recognize malignant disease involving the paracardiac spaces, myocardium, and pericardium. With a better understanding of the range of normal and abnormal patterns of cardiac FDG activity, important benign and malignant diseases involving the heart and pericardium can be recognized and diagnosed.

Post-Acute and Long-Term Care Patients Account for a Disproportionately High Number of Adverse Events in the Emergency Department.

OBJECTIVES: High rates of adverse events (AEs) are reported for post-acute and long-term care settings (PA/LTC: skilled nursing facilities, inpatient rehabilitation centers, long-term acute care facilities, and home health). However, emergency department (ED)-based studies in this area are lacking. We describe all-cause harm among patients from PA/LTC settings seen in the ED. DESIGN: Retrospective observational study using the ED Trigger Tool, with dual independent nurse reviews of 5582 ED records with triggers (findings increasing the likelihood of an AE) and confirmatory physician review of putative AEs. SETTING AND PARTICIPANTS: We captured data for all adult patients at an urban, academic ED over a 13-month period (92,859 visits). PA/LTC patients were identified using a computerized ED Trigger Tool and manual review (κ = 0.85). MEASURES: We characterize the AEs identified by severity and type using the ED Taxonomy of Adverse Events, and whether the AE occurred in the ED or was present on arrival. We estimate population AE rates using inverse probability weighting. RESULTS: Compared with non-PA/LTC patients, PA/LTC patients (4.4% of population; 8.2% of our sample) tended to be older (median age 69 vs 50 years), with comparable sex ratios (54% female overall). PA/LTC patients accounted for 21% of all AEs (26% present on arrival; 13% in ED). Rates of AEs occurring in the ED were comparable after matching on age. Present on arrival AEs from a PA/LTC setting were most commonly related to patient care (39%), medication (34%), and infections (16%). CONCLUSIONS AND IMPLICATIONS: PA/LTC patients account for a small proportion of ED visits but experience a disproportionate number of AEs that are primarily present on arrival and patient-care related, and contribute to an admission rate double that for non-PA/LTC patients. Arguably, this cohort represents PA/LTC patients with the most severe AEs. Understanding these AEs may help identify high-yield targets for quality improvement.

Multicenter Test of an Emergency Department Trigger Tool for Detecting Adverse Events.

OBJECTIVES: Traditional approaches to safety and quality screening in the emergency department (ED) are porous and low yield for identifying adverse events (AEs). A better approach may be in the use of trigger tool methodology. We recently developed a novel ED trigger tool using a multidisciplinary, multicenter approach. We conducted a multicenter test of this tool and assess its performance. METHODS: In design and participants, we studied the ED trigger tool for a 13-month period at four EDs. All patients 18 years and older with Emergency Severity Index acuity levels of 1 to 3 seen by a provider were eligible. Reviewers completed standardized training modules. Each site reviewed 50 randomly selected visits per month. A first-level reviewer screened for presence of predefined triggers (findings that increase the probability of an AE). If no trigger is present, the review is deemed complete. When present, a trigger prompts an in-depth review for an AE. Any event identified is assigned a level of harm using the Medication Event Reporting and Prevention (MERP) Index, ranging from a near miss (A) to patient death (I). Events are noted as present on arrival or in the ED, an act of commission or omission, and are assigned one of four event categories. A second-level physician performs a confirmatory review of all AEs and independently reviews 10% of cases to estimate the false-negative rate. All AEs or potential AEs were reviewed in monthly group calls for consensus on findings. The primary outcome is the proportion of visits in which an AE is identified, overall and by site. Secondary outcomes include categories of events, distribution of harm ratings, and association of AEs with sociodemographic and clinical factors and triggers. We present sociodemographic data and details about AEs and results of logistic regression for associations of AEs with of triggers, sociodemographics, and clinical variables. RESULTS: We captured 2594 visits that are representative, within site, of their patient population. Overall, the sample is 64% white, 54% female, and with a mean age of 51. Variability is observed between sites for age, race, and insurance, but not sex. A total of 240 events were identified in 228 visits (8.8%) of which 53.3% were present on arrival, 19.7% were acts of omission, and 44.6% were medication-related, with some variability across sites. A MERP F score (contributing to need for admission, higher level of care, or prolonged hospitalization) was the most common severity level (35.4% of events). Overall, 185 (77.1%) of 240 events involved patient harm (MERP level ≥ E), affecting 175 visits (6.7%). Triggers were present in 951 visits (36.6%). Presence of any trigger was strongly associated with an AE (adjusted odds ratio = 4.6, 95% confidence interval = 3.2-6.6). Ten triggers were individually associated with AEs (adjusted odds ratio = 2.1-7.7). Variability was observed across sites in individual trigger associations, event rates, and categories, but not in severity ratings of events. The overall false-negative rate was 6.1%. CONCLUSIONS: The trigger tool approach was successful in identifying meaningful events. The ED trigger tool seems to be a promising approach for identifying all-cause harm in the ED.

Does teamwork improve performance in the operating room? A multilevel evaluation.

BACKGROUND: Medical care is a team effort, especially as patient cases are more complex. Communication, cooperation, and coordination are vital to effective care, especially in complex service lines such as the operating room (OR). Team training, specifically the TeamSTEPPS training program, has been touted as one methodology for optimizing teamwork among providers and increasing patient safety. Although such team-training programs have transformed the culture and outcomes of other dynamic, high-risk industries such as aviation and nuclear power, evidence of team training effectiveness in health care is still evolving. Although providers tend to react positively to many training programs, evidence that training contributes to important behavioral and patient safety outcomes is lacking. METHOD: A multilevel evaluation of the TeamSTEPPS training program was conducted within the OR service line with a control location. The evaluation was a mixed-model design with one between-groups factor (TeamSTEPPS training versus no training) and two within-groups factors (time period, team). The groups were located at separate campuses to minimize treatment diffusion. Trainee reactions, learning, behaviors in the OR, and proxy outcome measures such as the Hospital Survey on Patient Safety Culture (HSOPS) and Operating Room Management Attitudes Questionnaire (ORMAQ) were collected. RESULTS: All levels of evaluation demonstrated positive results. The trained group demonstrated significant increases in the quantity and quality of presurgical procedure briefings and the use of quality teamwork behaviors during cases. Increases were also found in perceptions of patient safety culture and teamwork attitudes. DISCUSSION: The hospital system has integrated elements of TeamSTEPPS into orientation training provided to all incoming hospital employees, including nonclinical staff.

Description and Yield of Current Quality and Safety Review in Selected US Academic Emergency Departments.

OBJECTIVES: Quality and safety review for performance improvement is important for systems of care and is required for US academic emergency departments (EDs). Assessment of the impact of patient safety initiatives in the context of increasing burdens of quality measurement compels standardized, meaningful, high-yield approaches for performance review. Limited data describe how quality and safety reviews are currently conducted and how well they perform in detecting patient harm and areas for improvement. We hypothesized that decades-old approaches used in many academic EDs are inefficient and low yield for identifying patient harm. METHODS: We conducted a prospective observational study to evaluate the efficiency and yield of current quality review processes at five academic EDs for a 12-month period. Sites provided descriptions of their current practice and collected summary data on the number and severity of events identified in their reviews and the referral sources that led to their capture. Categories of common referral sources were established at the beginning of the study. Sites used the Institute for Healthcare Improvement's definition in defining an adverse event and a modified National Coordinating Council for Medication Error Reporting and Prevention (MERP) Index for grading severity of events. RESULTS: Participating sites had similar processes for quality review, including a two-level review process, monthly reviews and conferences, similar screening criteria, and a grading system for evaluating cases. In 60 months of data collection, we reviewed a total of 4735 cases and identified 381 events. This included 287 near-misses, errors/events (MERP A-I) and 94 adverse events (AEs) (MERP E-I). The overall AE rate (event rate with harm) was 1.99 (95% confidence interval = 1.62%-2.43%), ranging from 1.24% to 3.47% across sites. The overall rate of quality concerns (events without harm) was 6.06% (5.42%-6.78%), ranging from 2.96% to 10.95% across sites. Seventy-two-hour returns were the most frequent referral source used, accounting for 47% of the cases reviewed but with a yield of only 0.81% in identifying harm. Other referral sources similarly had very low yields. External referrals were the highest yield referral source, with 14.34% (10.64%-19.03%) identifying AEs. As a percentage of the 94 AEs identified, external referrals also accounted for 41.49% of cases. CONCLUSIONS: With an overall adverse event rate of 1.99%, commonly used referral sources seem to be low yield and inefficient for detecting patient harm. Approximately 6% of the cases identified by these criteria yielded a near miss or quality concern. New approaches to quality and safety review in the ED are needed to optimize their yield and efficiency for identifying harm and areas for improvement.

Development of an Emergency Department Trigger Tool Using a Systematic Search and Modified Delphi Process.

OBJECTIVE: This study aimed to develop an emergency department (ED) trigger tool to improve the identification of adverse events in the ED and that can be used to direct patient safety and quality improvement. This work describes the first step toward the development of an ED all-cause harm measurement tool by experts in the field. METHODS: We identified a multidisciplinary group of emergency medicine safety experts from whom we solicited candidate triggers. We then conducted a modified Delphi process consisting of 4 stages as follows: (1) a systematic literature search and review, including an independent oversampling of review for inclusion, (2) solicitation of empiric triggers from participants, (3) a Web-based survey ranking triggers on specific performance constructs, and (4) a final in-person meeting to arrive at consensus triggers for testing. Results of each step were shared with participants between each stage. RESULTS: Among an initial 804 unique articles found using our search criteria, we identified 94 that were suitable for further review. Interrater reliability was high (κ = 0.80). Review of these articles yielded 56 candidate triggers. These were supplemented by 58 participant-submitted triggers yielding a total of 114 candidate triggers that were shared with team members electronically along with their definitions. Team members then voted on each measure via a Web-based survey, ranking triggers on their face validity, utility for quality improvement, and fidelity (sensitivity/specificity). Participants were also provided the ability to flag any trigger about which they had questions or they felt merited further discussion at the in-person meeting. Triggers were ranked by combining the first 2 categories (face validity and utility), and information on fidelity was reviewed for decision making at the in-person meeting. Seven redundant triggers were eliminated. At an in-person meeting including representatives from all facilities, we presented the 50 top-ranked triggers as well as those that were flagged on the survey by 2 or more participants. We reviewed each trigger individually, identifying 41 triggers about which there was a clear agreement for inclusion. Of the seven additional triggers that required subsequent voting via e-mail, 5 were adopted, arriving at a total of 46 consensus-derived triggers. CONCLUSIONS: Our modified Delphi process resulted in the identification of 46 final triggers for the detection of adverse events among ED patients. These triggers should be pilot field tested to quantify their individual and collective performance in detecting all-cause harm to ED patients.

Critical Review, Development, and Testing of a Taxonomy for Adverse Events and Near Misses in the Emergency Department.

OBJECTIVES: An adverse event (AE) is a physical harm experienced by a patient due to health care, requiring intervention. Describing and categorizing AEs is important for quality and safety assessment and identifying areas for improvement. Safety science suggests that improvement efforts should focus on preventing and mitigating harm rather than on error, which is commonplace but infrequently leads to AEs. Most taxonomies fail to describe harm experienced by patients (e.g., hypoxia, hemorrhage, anaphylaxis), focusing instead on errors, and use categorizations that are too broad to be useful (e.g., "communication error"). We set out to create a patient-centered, emergency department (ED)-specific framework for describing AEs and near misses to advance quality and safety in the acute care setting. METHODS: We performed a critical review of existing taxonomies of harm, evaluating their applicability to the ED. We identified and adopted a classification framework and developed a taxonomy using an iterative process categorizing approximately 600 previously identified AEs and near misses. We reviewed this taxonomy with collaborators at four medical centers, receiving feedback and providing clarification. We then disseminated a set of representative scenarios for these safety experts to categorize independently using the taxonomy. We calculated interrater reliability and performance compared to our criterion standard. RESULTS: Our search identified candidate taxonomies for detailed review. We selected the Adventist Health Systems AE taxonomy and modified this for use in the ED, adopting a framework of categories, subcategories, and up to three modifiers to further describe events. On testing, overall reviewer agreement with the criterion standard was 92% at the category level and 88% at the subcategory level. Three of the four raters concurred in 55 of 59 scenarios (93%) and all four concurred in 46 of 59 scenarios (78%). At the subcategory level, there was complete agreement in 40 of 59 (68%) scenarios and majority agreement in 55 of 59 instances (93%). Performance of individual raters ranged from very good (88%, 52/59) to near perfect (98%, 58/59) at the main category level. CONCLUSIONS: We developed a taxonomy of AEs and near misses for the ED, modified from an existing framework. Testing of the tool with minimal training yielded high performance and good inter-rater reliability. This taxonomy can be adapted and modified by EDs seeking to enhance their quality and safety reviews and characterize harm occurring in their EDs for quality improvement purposes.

Impact of Inpatient Harms on Hospital Finances and Patient Clinical Outcomes.

OBJECTIVE: The aim of this study was to determine the impact of all-cause inpatient harms on hospital finances and patient clinical outcomes. RESEARCH DESIGN: A retrospective analysis of inpatient harm from 24 hospitals in a large multistate health system was conducted during 2009 to 2012 using the Institute of Healthcare Improvement Global Trigger Tool for Measuring Adverse Events. Inpatient harms were detected and categorized into harm (F-I), temporary harm (E), and no harm. RESULTS: Of the 21,007 inpatients in this study, 15,610 (74.3%) experienced no harm, 2818 (13.4%) experienced temporary harm, and 2579 (12.3%) experienced harm. A patient with harm was estimated to have higher total cost ($4617 [95% confidence interval (CI), $4364 to 4871]), higher variable cost ($1774 [95% CI, $1648 to $1900]), lower contribution margin (-$1112 [95% CI, -$1378 to -$847]), longer length of stay (2.6 d [95% CI, 2.5 to 2.8]), higher mortality probability (59%; odds ratio, 1.4 [95% CI, 1.0 to 2.0]), and higher 30-day readmission probability (74.4%; odds ratio, 2.9 [95% CI, 2.6 to 3.2]). A patient with temporary harm was estimated to have higher total cost ($2187 [95% CI, $2008 to $2366]), higher variable cost ($800 [95% CI, $709 to $892]), lower contribution margin (-$669 [95% CI, -$891 to -$446]), longer length of stay (1.3 d [95% CI, 1.2 to 1.4]), mortality probability not statistically different, and higher 30-day readmission probability (54.6%; odds ratio, 1.2 [95% CI, 1.1 to 1.4]). Total health system reduction of harm was associated with a decrease of $108 million in total cost, $48 million in variable cost, an increase of contribution margin by $18 million, and savings of 60,000 inpatient care days. CONCLUSIONS: This all-cause harm safety study indicates that inpatient harm has negative financial outcomes for hospitals and negative clinical outcomes for patients.

F-18 fluorodeoxyglucose-positron emission tomography imaging for primary breast cancer and loco-regional staging.

Breast cancer is the most common female malignancy in Western countries. The limitations of mammography, ultrasound and MRI do not allow reliable identification of primary breast cancer at early stages. Functional breast imaging with positron emission tomography (PET) and F-18 fluorodeoxyglucose (FDG) enables the visualization of increased glucose metabolism of breast cancer. However, despite the successful identification of primary breast cancer, FDG-PET provides a low sensitivity to detect small tumors. Therefore, FDG-PET does not allow screening of asymptomatic women and cannot be used to exclude breast cancer in patients with suspicious breast masses or abnormal mammography. FDG-PET is a powerful tool for staging of breast cancer patients, but does not detect micrometastases and small tumor infiltrated lymph nodes. Nevertheless, in patients with locally advanced breast cancer, PET accurately determines the extent of disease, particularly the loco-regional lymph node status. Advances in technology, for example the development of dedicated breast imaging devices such as positron emission mammography, hold promise to improve the detection of primary tumors in the future.

Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody.

Positron emission tomography (PET) provides an effective means of both diagnosing/staging several types of cancer and evaluating efficacy of treatment. To date, the only U.S. Food and Drug Administration-approved radiotracer for oncologic PET is (18)F-fluoro-deoxyglucose, which measures glucose accumulation as a surrogate for malignant activity. Engineered antibody fragments have been developed with the appropriate targeting specificity and systemic elimination properties predicted to allow for effective imaging of cancer based on expression of tumor associated antigens. We evaluated a small engineered antibody fragment specific for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotracer when labeled with iodine-124. Our studies revealed HER2-dependent imaging of mouse tumor xenografts with a time-dependent increase in tumor-to-background signal over the course of the experiments. Radioiodination via an indirect method attenuated uptake of radioiodine in tissues that express the Na/I symporter without affecting the ability to image the tumor xenografts. In addition, we validated a method for using a clinical PET/computed tomography scanner to quantify tumor uptake in small-animal model systems; quantitation of the tumor targeting by PET correlated with traditional necropsy-based analysis at all time points analyzed. Thus, diabodies may represent an effective molecular structure for development of novel PET radiotracers.

The integration of 18-fluoro-deoxy-glucose positron emission tomography and endoscopic ultrasound in the treatment-planning process for esophageal carcinoma.

PURPOSE: Accurate delineation of the gross tumor volume (GTV) is important in radiation therapy treatment planning. We evaluated the impact of PET and endoscopic ultrasound (EUS) compared with CT simulation in the planning of radiation fields for patients with esophageal carcinoma. MATERIAL AND METHODS: Twenty-five patients presenting with esophageal carcinoma for radiation therapy underwent PET scans in the treatment position after conventional CT simulation. Patients underwent PET/CT scanning after being injected with 10 to 20 mCi of [F-18]-2-deoxy-2-fluro-D-glucose. The length of the abnormality seen on the CT portion of the PET/CT scan vs. the PET scan alone was determined independently by 2 separate investigators. The length of the GTV and detection of regional adenopathy by PET was also correlated with EUS in 18 patients. Of the 18 patients who had EUS, 2 had T2 tumors and 16 had T3 tumors. Eighteen patients had adenocarcinoma and 7 had squamous cell carcinoma. Nine tumors were located at the gastroesophageal junction, 8 at the lower esophagus, 7 in the middle esophagus, and 1 in the cervical esophagus. The PET scans were reviewed to determine the length of the abnormality by use of a standard uptake value (SUV) of 2.5 to delineate the tumor extent. RESULTS: The mean length of the cancer was 5.4 cm (95% CI 4.4-6.4 cm) as determined by PET scan, 6.77 cm (95% CI, 5.6-7.9 cm) as determined by CT scan, and 5.1 cm (95% CI, 4.0-6.1 cm) for the 22 patients who had endoscopy. The length of the tumors was significantly longer as measured by CT scans compared with PET scans (p = 0.0063). EUS detected significantly more patients with periesophageal and celiac lymphadenopathy compared to PET and CT. The SUV of the esophageal tumors was higher in patients with peri-esophageal lymphadenopathy identified on PET scans. CONCLUSION: Endoscopic ultrasound and PET scans can add additional information to aid the radiation oncologist's ability to precisely identify the GTV in patients with esophageal carcinoma.

Positron emission mammography: high-resolution biochemical breast imaging.

Positron emission mammography (PEM) provides images of biochemical activity in the breast with spatial resolution matching individual ducts (1.5 mm full-width at half-maximum). This spatial resolution, supported by count efficiency that results in high signal-to-noise ratio, allows confident visualization of intraductal as well as invasive breast cancers. Clinical trials with a full-breast PEM device have shown high clinical accuracy in characterizing lesions identified as suspicious on the basis of conventional imaging or physical examination (sensitivity 93%, specificity 83%, area under the ROC curve of 0.93), with high sensitivity preserved (91%) for intraductal cancers. Increased sensitivity did not come at a cost of reduced specificity. Considering that intraductal cancer represents more than 30% of reported cancers, and is the form of cancer with the highest probability of achieving surgical cure, it is likely that the use of PEM will complement anatomic imaging modalities in the areas of surgical planning, high-risk monitoring, and minimally invasive therapy. The quantitative nature of PET promises to assist researchers interested studying the response of putative cancer precursors (e.g., atypical ductal hyperplasia) to candidate prevention agents.

Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer.

BACKGROUND: High-resolution positron-emission mammography (PEM) is a new device, which allows the imaging of breast tissue. A prospective study was performed to assess the accuracy of PEM in newly diagnosed breast cancer patients. METHODS: In a prospective multicenter study, 44 women with confirmed breast cancers were imaged with a high-resolution PEM scanner (Naviscan PET Systems, Rockville, MD) with 18F-fluorodeoxyglucose. The images were blindly evaluated and were compared with final pathology. RESULTS: The majority of the index lesions were seen on PEM (89%, 39/44). PEM detected 4 of 5 incidental breast cancers, 3 of which were not seen by any other imaging modalities. Of 19 patients undergoing breast-conserving surgery, PEM correctly predicted 6 of 8 (75%) patients with positive margins and 100% (11/11) with negative margins. CONCLUSION: The current PEM device shows promise in detecting breast malignancies and may assist in the planning of adequate partial mastectomy procedures to better ensure negative margins.

Characterization of the normal adrenal gland with 18F-FDG PET/CT.

UNLABELLED: Prior studies have documented increased (18)F-FDG adrenal activity in both benign and malignant pathologic conditions. When whole-body PET imaging is performed without CT anatomic coregistration, however, the normal adrenal gland is difficult to recognize. The purpose of this study was to investigate the normal adrenal appearance and standardized uptake value (SUV) using (18)F-FDG PET/CT imaging. METHODS: Twenty patients with lymphoma with normal-appearing adrenal glands on prior CT examination (less than a 5% pretest likelihood of adrenal involvement) were studied. PET/CT imaging was performed 2 h after intravenous administration of (18)F-FDG. Unenhanced CT scans were acquired for attenuation correction and anatomic coregistration. PET images were reconstructed using an ordered-subsets expectation maximization algorithm and were corrected for body weight, dose, and radioactive decay. Ability to confirm visualization of the adrenal glands was determined for (18)F-FDG PET alone and for (18)F-FDG PET/CT by a consensus of 2 readers, and uptake of (18)F-FDG in the adrenal gland was compared with liver activity and scored visually (0 = no visualization, 1 = activity less than in liver, 2 = activity equal to liver activity, and 3 = activity greater than in liver). RESULTS: The 2 readers agreed on visualization of the adrenal glands with PET alone for 2 of 40 (5%) glands. With PET/CT, the readers agreed on visualization of 27 of 40 (68%) adrenal glands. Visual scores for normal adrenal activity ranged from 0 to 3, and maximum SUVs ranged from 0.95 to 2.46. Visual scoring of adrenal activity correlated well with both mean and maximal SUV (mean SUV vs. visual score: slope = 0.96, r = 0.88; maximum SUV vs. visual score: slope = 0.99, r = 0.87). CONCLUSION: PET/CT permits more reliable visualization of normal adrenal glands than does PET alone. Visual assessment of adrenal uptake correlates well with SUV measurement, and readers of PET/CT need to be aware of the wide range of normal adrenal uptake.

Quantitation of small-animal (124)I activity distributions using a clinical PET/CT scanner.

UNLABELLED: Time-dependent PET imaging can be an important tool in the assessment of radiotracer performance in murine models. We have performed a quantitative analysis of PET images of (124)I, acquired on a clinical PET system using a small-animal phantom. We then compared the recovered activity concentrations with the known activity concentration in the phantom spheres. The recovery coefficients found from the phantom data were applied to in vivo (124)I anti-HER2/neu C6.5 diabody PET data and compared with necropsy biodistribution data from the same tumor-bearing immunodeficient mouse. METHODS: The small-animal phantom consisted of a 4 x 8 cm water-filled acrylic cylinder with hollow spheres filled with water ranging in volume from 0.0625 to 1.0 mL and activity concentration of 27 +/- 2 kBq/mL. The background activity concentrations varied from 0 to 0.05 to 0.10 of the spheres. Data were acquired at 0, 5, and 10 cm from the scanner longitudinal axis. Recovery coefficients were theoretically calculated for spheres of different volume, background-to-target concentrations, and distance from the scanner's longitudinal axis. The theoretic recovery coefficients were applied to the maximum sphere activity concentration measured from the PET images, thus obtaining a recovered activity concentration to be compared with the known activity concentration of the spheres. RESULTS: The mean recovered activity concentration for the phantom spheres was 25 +/- 2 kBq/mL. The (124)I diabody PET image of a mouse with a tumor xenograft was then analyzed using the techniques described. The tumor percentage injected dose per gram estimated from the murine PET image (4.8 +/- 0.4) compared well with those obtained from necropsy studies (5.1). CONCLUSION: This study indicates the feasibility of performing quantitative imaging on murine (124)I antibody fragment PET images using a large-bore clinical scanner, which enables high-throughput studies to evaluate the performance of PET tracers in a timely and cost-effective manner by imaging multiple animals simultaneously. Tracers deemed promising by this screening method can then be further evaluated using traditional necropsy studies. Our group is currently conducting time-dependent (124)I diabody PET and necropsy comparative studies with larger numbers of mice.

Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia.

PURPOSE: To examine the impact of a unique evidence-based clinical pathway on six outcomes of care in patients hospitalized for community-acquired pneumonia (CAP). METHODS: A retrospective cohort study of CAP patients discharged between January 1999 and December 2001, from 31 Adventist Health System institutions nationwide. A total of 22,196 records were available for multivariate analyses. Odds ratios (OR) for the outcomes were calculated and stratified by a unique severity score. The severity score ranged from 1 to 5, where 5 indicated the most severe condition. RESULTS: Pathway patients were significantly less likely to die in-hospital compared with non-pathway patients in four of the five severity strata (OR in severity level 1=0.37; 95% confidence interval [CI], 0.20-0.70). In all severity strata, pathway patients were approximately twice as likely as non-pathway patients to receive blood cultures and appropriate antibiotic therapy. Among patients who were classified as severity level 1, pathway patients experienced an 80% reduction in the odds of respiratory failure requiring mechanical ventilation (OR=0.20; 95% CI, 0.12-0.33). CONCLUSIONS: Patients who were placed on pneumonia clinical pathway care were much more likely than non-pathway patients to have favorable outcomes of care.

Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a preliminary study.

[F18]-2-deoxy-2fluoro-D-glucose positron emission tomography (FDG-PET) is increasingly used in the diagnosis and staging of lung cancer. Despite its positive performance characteristics in non-small cell lung cancer (NSCLC), the role of FDG-PET in the staging of small cell lung cancer (SCLC) remains to be determined. We designed a prospective study to address this question. Eighteen patients with SCLC were enrolled prospectively to undergo total body FDG-PET in addition to conventional staging procedures (chest computed tomography (CT), abdominal CT, cranial CT or magnetic resonance imaging (MRI), and bone scan/bone marrow biopsy). The agreement between FDG-PET and conventional staging modalities in identifying the presence or absence of metastatic disease was compared using the Veterans Administration (VA) cooperative staging system for staging. Overall staging by FDG-PET agreed with conventional staging exams in 15/18 (83%) patients (kappa=0.67), which included eight extensive and seven limited cases. FDG-PET showed more extensive disease in two of the three patients for which FDG-PET and conventional staging disagreed. These data suggest that total body FDG-PET may be useful in the staging, treatment planning, and prognostication of SCLC. Whether FDG-PET will replace other more established staging modalities remains to be determined by larger prospective randomized controlled studies.

Radiation dosimetry of florbetapir F 18.

BACKGROUND: Florbetapir is one of several 18F-labeled amyloid plaque imaging tracers for positron emission tomography (PET). As the bio-distribution and radiation dose of PET tracers in human research are important for estimating the relative risks and benefits, a study was conducted to obtain this information on florbetapir. METHODS: Nine cognitively normal subjects (six females and three males, age 58 ± 10 years, weight 81 ± 17 kg) received an intravenous bolus injection of 395 ± 27.9 MBq of florbetapir, and whole-body emission scans were performed over approximately 6 h. Computed tomography scans were acquired for attenuation correction. Volumes of interest (VOIs) for source organs including the brain, liver, lung, heart wall, and vertebrae were defined on the PET images. The VOIs of the gallbladder, urinary bladder, and large and small intestines were also defined. Using reference man organ volumes (ICRP 30), total activity was calculated per organ for each time point. The resultant time-activity curves (TACs) were fitted with constrained exponentials. Kinetic data were entered into OLINDA/EXM software to calculate dose estimates; the dynamic urinary bladder and ICRP 30 GI tract models were employed. The effective dose (ED) for each subject was estimated from the acquired data using the adult model. RESULTS: The mean ED determined for nine healthy volunteers was 18.60 ± 4.26 µSv/MBq or 6.88 mSv for a 370-MBq dose. The organs that received the highest radiation absorbed doses were the gallbladder, upper large intestine, small intestine, liver, and urinary bladder at 143.0 ± 80.20, 74.50 ± 34.20, 65.50 ± 29.60, 64.40 ± 22.10, and 27.10 ± 11.70 µSv/MBq, respectively. CONCLUSIONS: The ED for florbetapir has been calculated for nine healthy volunteers. At a dose of 370 MBq florbetapir, the total average ED is approximately 6.88 mSv.