COVID-19 Vaccine Policy Implementation and Differential Vaccine Uptake Trajectories in Chicago Communities.

BACKGROUND: Since the onset of the COVID-19 pandemic, multiple public health interventions have been implemented to respond to the rapidly evolving pandemic and community needs. This article describes the scope, timing, and impact of coordinated strategies for COVID-19 vaccine uptake in Chicago for the first year of vaccine distribution. METHODS: Using a series of interviews with public health officials and leaders of community-based organizations (CBOs) who participated in the implementation of the citywide COVID-19 vaccine outreach initiatives, we constructed a timeline of vaccine outreach initiatives. The timeline was matched to the vaccine uptake rates to explore the impact of the vaccine outreach initiatives by community area. Finally, we discussed the nature of policy initiatives and the level of vaccine uptake in relation to community characteristics. RESULTS: The Chicago Department of Public Health (CDPH) implemented myriad vaccine outreach strategies, including mass vaccination sites, improved access, and community-level vaccine campaigns. Protect Chicago+ was the primary vaccine outreach effort initiated by the CDPH, which identified 15 highly vulnerable community areas. More than 2.7 million (67%) Chicagoans completed the vaccine regimen by December 2021. Black (51.3%) Chicagoans were considerably less likely to be vaccinated than Asian (77.6%), White (69.8%), and Hispanic (63.6%) Chicago residents. In addition, there were significant spatial differences in the rate of COVID-19 vaccine completion: predominantly White and Hispanic communities, compared with Black communities, had higher rates of vaccine completion. CONCLUSIONS: The community outreach efforts to improve COVID-19 vaccine uptake in Chicago have shown the importance of community-engaged approaches in pandemic responses. Despite citywide efforts to build community infrastructure, Black communities had relatively lower levels of vaccine uptake than other communities. Broader social restructuring to mitigate disinvestment and residential segregation and to ameliorate medical mistrust will be needed to prepare for future pandemics and disasters.

Bayesian functional data analysis over dependent regions and its application for identification of differentially methylated regions.

We consider a Bayesian functional data analysis for observations measured as extremely long sequences. Splitting the sequence into several small windows with manageable lengths, the windows may not be independent especially when they are neighboring each other. We propose to utilize Bayesian smoothing splines to estimate individual functional patterns within each window and to establish transition models for parameters involved in each window to address the dependence structure between windows. The functional difference of groups of individuals at each window can be evaluated by the Bayes factor based on Markov Chain Monte Carlo samples in the analysis. In this paper, we examine the proposed method through simulation studies and apply it to identify differentially methylated genetic regions in TCGA lung adenocarcinoma data.

Lipidomics, Acute Ischemic Stroke, Symptoms, and Outcomes: Observational Study Protocol.

BACKGROUND: Acute ischemic stroke is one of the leading causes of death and disability globally. Recent advances in omics methodology enable lipidomic profiling, which may provide knowledge of the underlying pathology of acute ischemic stroke and its associated outcomes. OBJECTIVE: This study aims to examine the longer-term relationships between symptoms and outcomes following acute ischemic stroke and the underlying lipidomic signatures over 6 months during recovery between acute ischemic stroke patients who received reperfusion therapies and those who did not. METHODS: This prospective cohort study will enroll 104 participants post-acute ischemic stroke in two groups based on their receipt of reperfusion therapy (Group 1) or not (Group 2; n = 52/group). Peripheral plasma samples will be collected from both groups for lipidomic analysis over 6 months. Arterial blood samples will be collected during the procedure for those receiving reperfusion. Self-reported symptoms and outcome data will be collected from both groups. DISCUSSION: We will compare and examine the associations among plasma lipidomic biomarkers and symptoms and cognitive, functional, and health-related quality of life outcomes over 6 months between acute ischemic stroke patients who did and did not receive reperfusion intervention.

Pragmatic Clinical Trial to Improve Patient Experience Among Adults During Transitions from Hospital to Home: the PArTNER study.

INTRODUCTION: Minority-serving hospitals (MSHs) need evidence-based strategies tailored to the populations they serve to improve patient-centered outcomes after hospitalization. METHODS: We conducted a pragmatic randomized clinical trial (RCT) from October 2014 to January 2017 at a MSH comparing the effectiveness of a stakeholder-supported Navigator intervention vs. Usual care on post-hospital patient experience, outcomes, and healthcare utilization. Community health workers and peer coaches delivered the intervention which included (1) in-hospital visits to assess barriers to health/healthcare and to develop a personalized Discharge Patient Education Tool (DPET); (2) a home visit to review the DPET; and (3) telephone-based peer coaching. The co-primary outcomes were between-group comparisons of 30-day changes in Patient-Reported Outcomes Measurement Information System (PROMIS) measures of anxiety and informational support (minimum important difference is 2 to 5 units change); a p-value <0.025 was considered significant using intention-to-treat analysis. Secondary outcomes included death, ED visits, or readmissions and measures of emotional, social, and physical health at 30 and 60 days. RESULTS: We enrolled 1029 adults hospitalized with heart failure (28%), pneumonia (22%), MI (10%), COPD (11%), or sickle cell disease (29%). Over 80% were non-Hispanic Black. Overall, there were no significant between-group differences in the 30-day change in anxiety (adjusted difference: -1.6, 97.5% CI -3.3 to 0.1, p=0.03), informational support (adjusted difference: -0.01, 97.5% CI -2.0 to 1.9, p=0.99), or any secondary outcomes. Exploratory analyses suggested the Navigator intervention improved anxiety among participants with COPD, a primary care provider, a hospitalization in the past 12 months, or higher baseline anxiety; among participants without health insurance, the intervention improved informational support (all p-values <0.05). CONCLUSIONS: In this pragmatic RCT at a MSH, the Navigator intervention did not improve post-hospital anxiety, informational support, or other outcomes compared to Usual care. Benefits observed in participant subgroups should be confirmed in future studies. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02114515.

Redefining the Risk of Surgery for Clinical Stage IIIA (N2) Non-Small Cell Lung Cancer: A Pooled Analysis of the STS GTSD and ESTS Registry.

BACKGROUND: Management of clinical stage IIIA-N2 (cIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. We evaluated treatment strategies and outcomes in cIIIA-N2 NSCLC patients who underwent pulmonary resection in The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) and the European Society of Thoracic Surgeons (ESTS) Registry. METHODS: The STS GTSD and ESTS Registry were queried for patients who underwent pulmonary resection for cIIIA-N2 NSCLC between 2012 and 2016. Demographic variables, treatment strategies, and outcome measures were collected and analyzed. Significance of differences was determined using the χ2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. RESULTS: Pulmonary resection was performed in 4279 cIIIA-N2 NSCLC patients (2928 STS GTSD; 1351 ESTS). Induction therapy was administered to 49%. Lobectomy was performed in 67.1% and pneumonectomy in 13%. Lobectomy was associated with 19.2% major morbidity and 1.6% operative mortality, while pneumonectomy was associated with 34.1% and 5%, respectively. Induction therapy was associated with a higher rate of major morbidity or mortality than upfront surgery (23.2% vs 19.5%, p = 0.004), driven by pneumonectomy (40.7% vs 30.3%, p = 0.012) rather than lobectomy (20.3% vs 18.8%, p = 0.31). CONCLUSIONS: Pulmonary resection for cIIIA-N2 NSCLC is associated with low rates of operative morbidity and mortality, with lobectomy having lower morbidity and mortality than pneumonectomy. Induction therapy, particularly chemoradiotherapy, is associated with a higher rate of composite morbidity or mortality than upfront surgery in pneumonectomy patients but not lobectomy patients.

Evaluation of the impact of cachexia on clinical outcomes in aggressive lymphoma.

Cancer cachexia is a state of involuntary weight loss and altered body composition triggered by an underlying malignancy. We sought to correlate measures of cachexia with clinical outcomes in aggressive lymphomas and to identify biological pathways involved in the cachexia phenotype for possible druggable targets. Radiographic measures of cachexia were collected in a retrospective cohort of 109 patients with aggressive B-cell lymphoma and followed for clinical outcome. We found males with sarcopenia had reduced progression-free survival (5·4 vs. 72·3 months, P < 0·0005) and overall survival (OS; 30·2 months vs. not reached, NR, P = 0·02); males with adipopenia also had decreased OS (21·6 months vs. NR, P = 0·04). A trend for increased OS was observed in female sarcopenics only (32·8 months vs. NR, P = 0·08). Additionally, we analysed a prospective cohort of 14 patients for differences in circulating molecular targets involved in various biological pathways. There was a significant correlation with cachexia for reduced serum levels of mediators within the glucose utilization [insulin -like growth factor (IGF)-binding protein 6, P = 0·04; IGF-1, P = 0·02], inflammation (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells; LIGHT, P = 0·005), and energy intake/expenditure (leptin, P = 0·004). We conclude that cachexia in patients with aggressive lymphomas has sex-specific prognostic utility and correlates with measurable changes in metabolism and immune function.

Description and analysis of patients and outcomes following third-time heart transplantation: An analysis of the United Network for Organ Sharing database from 1985 to 2017.

BACKGROUND: Following second heart transplantation (HTx), some patients experience graft failure and require third-time heart transplantation. Little data exist to guide decision-making with regard to repeat retransplantation in older patients. METHODS: We performed a retrospective cohort analysis of patients receiving a third HTx, as identified in the United Network for Organ Sharing (UNOS) database from 1985 to 2017. RESULTS: The study cohort consisted of N = 60 patients, with an average age of 29 with a standard deviation of ±18 years. Overall survival for the cohort at 1, 5, and 10 years is 83%, 64%, and 44%, respectively. The rate of third-time HTxs has steadily increased in all age groups. Patients older than 50 years now account for 18.3% of all third-time HTxs. Although this group demonstrated longer average previous graft survival, after third HTx they demonstrate significantly poorer survival outcomes compared to third-time HTx recipients younger than 21 (P = 0.05). Age over 50, BMI over 30, and diabetes were all found to be independent risk factors for decreased survival following third HTx. CONCLUSIONS: We describe trends in patients undergoing third HTx. We highlight subsets of such recipients who exhibit decreased survival.

EXTERNAL VALIDATION OF A PREDICTIVE MODEL FOR ACUTE PANCREATITIS RISK IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA.

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model. Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride [TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC). Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age. Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options. Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level.

The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients.

BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes. METHODS: Serum samples were prospectively collected from 57 patients receiving salvage chemotherapy and 70 non-EGFR mutated patients receiving erlotinib. Patients were classified as either VeriStrat good or poor based on the VeriStrat test. Luminex immunoassays were used to measure circulating levels of 102 distinct biomarkers implicated in tumor aggressiveness and treatment resistance. A Cox PH model was used to evaluate associations between biomarker levels and clinical outcome, whereas the association of VeriStrat classifications with biomarker levels was assessed via the Mann-Whitney Rank Sum test. RESULTS: VeriStrat was prognostic for outcome within the erlotinib treated patients (HR = 0.29, p < 0.0001) and predictive of differential treatment benefit between erlotinib and chemotherapy ((interaction HR = 0.25; interaction p = 0.0035). A total of 27 biomarkers out of 102 unique analytes were found to be significantly associated with OS (Cox PH p ≤ 0.05), whereas 16 biomarkers were found to be associated with PFS. Thrombospondin-2, C-reactive protein, TNF-receptor I, and placental growth factor were the analytes most highly associated with OS, all with Cox PH p-values ≤0.0001. VeriStrat status was found to be significantly associated with 23 circulating biomarkers (Mann-Whitney Rank Sum p ≤ 0.05), 6 of which had p < 0.001, including C-reactive protein, IL-6, serum amyloid A, CYFRA 21.1, IGF-II, osteopontin, and ferritin. CONCLUSIONS: Strong associations were observed between survival and VeriStrat classifications as well as select circulating biomarkers associated with fibrosis, inflammation, and acute phase reactants as part of this study. The associations between these biomarkers and VeriStrat classification might have therapeutic implications for poor prognosis NSCLC patients, particularly with new immunotherapeutic treatment options.

Metastasectomy following incomplete response to high-dose interleukin-2.

OBJECTIVE: To evaluate our experience with metastasectomy following partial response or stable disease after treatment with high-dose interleukin-2 (HD IL-2). METHODS: A total of 305 patients with metastatic renal cell carcinoma or melanoma treated with HD IL-2 over a 12-year period were reviewed. Age, objective response, and overall survival data were evaluated using standard RECIST criteria and Kaplan-Meier estimates. RESULTS: The average age was 55.3 years (range, 15-85) and 245 (80.3%) patients had melanoma and 60 (19.7%) had renal cell carcinoma. The objective response rate to IL-2 for all patients was 13.6% and median survival was 16.8 months. Complete follow-up data were available for 236 patients with 147 (62.3%) progressing after treatment and 8 (3.3%) with a complete response. Incomplete responses were seen in 81 (34.3%) patients, including 57 (24.2%) patients with stable disease and 24 (10.1%) with partial responses. Of these 81 incomplete responders, 15 (18.5%) underwent subsequent metastasectomy. Patients without surgery had overall survival of 38.2 months and median survival has not yet been reached in those who underwent metastasectomy (P = 0.026). CONCLUSION: The data support prospective evaluation of metastasectomy following incomplete therapeutic responses to immunotherapy and defines a new role for surgical resection following IL-2 and perhaps other immunotherapy regimens.

ACUTE PANCREATITIS IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA IN A MULTI-ETHNIC MINORITY POPULATION.

OBJECTIVE: To investigate the prevalence and predictors of hypertriglyceridemic acute pancreatitis (HTG-AP) in a multi-ethnic minority population. METHODS: A retrospective, cross-sectional study from 2003 to 2013 of 1,157 adults with a serum triglyceride (TG) level ≥1,000 mg/dL comparing baseline characteristics and risk factors between those with and without HTG-AP. RESULTS: Mean study population age was 49.2 ± 11.5 years; 75.6% were male, 31.6% African American, 38.4% Hispanic, 22.7% Caucasian, 5.7% Asian, and 1.6% Pacific Islander. Prevalence of HTG-AP was 9.2%. Patients with HTG-AP were significantly younger (41.3 years vs. 50.0 years; P<.001) than those without HTG-AP. Excessive alcohol intake (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.5 to 6.0; P<.001), gallstone disease (OR, 3.9; 95% CI, 1.4 to 10.8; P = .008), and TG >2,000 mg/dL (OR, 4.8; 95% CI, 3.1 to 7.4; P<.001) remained significant independent risk factors. TG levels for patients with HTG-AP were higher (median TG, 2,394 mg/dL; interquartile range [IQR], 1,152 to 4,339 mg/dL vs. median TG, 1,406 mg/dL; IQR, 1,180.7 to 1,876.5 mg/dL). TG levels >2,000 mg/dL were associated with higher incidence of AP (22% vs. 5%). Patients with TG levels <2,000 mg/dL and no risk factors had prevalence of 2% compared to 33.6% with one risk factor and TG >2,000 mg/dL. Patients with HTG-AP had higher incidence of diabetic ketoacidosis at admission (7.5% vs. 2.5%; P = .004). CONCLUSION: TG level ≥2,000 mg/dL is associated with higher HTG-AP prevalence in ethnic minorities. Presence of excessive alcohol intake and/or gallstones further accentuates risk. ABBREVIATIONS: AP = acute pancreatitis; CT = computed tomography; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; HTG = hyper-triglyceridemia; HTG-AP = hypertriglyceridemic acute pancreatitis; ROC = receiver operating characteristic; TG = triglyceride.

Impact of treatment variability on survival in immuno-competent and immuno-compromised patients with primary central nervous lymphoma.

Patients with primary central nervous system lymphoma (PCNSL) treated in the 'real-world' setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/- rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/- systemic therapy). Fifty-eight of 108 patients received rituximab. Twenty-nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow-up of 18·7 months, median overall survival (OS) was 65·2 months. In univariate analysis, HD-MTX (median OS 72·7 vs. 2·7 months, P < 0·001) and rituximab (median not reached versus 28·4 months, P = 0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P = 0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno-competent/compromised patients and similar to those achieved in recent clinical trials.

Impact of cachexia on outcomes in aggressive lymphomas.

Cancer cachexia is defined as a state of involuntary weight loss, attributed to altered body composition with muscle mass loss and/or loss of adiposity. Identifying the association between cancer cachexia and outcomes may pave the way for novel agents that target the cancer cachexia process. Clinical parameters for measurement of cancer cachexia are needed. We conducted a single-institution retrospective analysis that included 86 NHL patients with the aim of identifying an association between cancer cachexia and outcomes in aggressive lymphomas using the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87-93, 15). Impact of cachexia factors on progression-free survival (PFS) and overall survival (OS) were assessed using log-rank test and Cox proportional hazards regression. Patients were dichotomized around the median CXI into "non-cachectic" (CXI ≥49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups. Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR = 4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is prognostic in aggressive lymphomas and implies that novel therapeutic strategies directed at reversing cachexia may improve survival in this population.

Enhancement of Ovarian Tumor Detection by DR6-Targeted Ultrasound Imaging Agents in Laying Hen Model of Spontaneous Ovarian Cancer.

OBJECTIVE: The lack of an effective early detection test leads to high case to death ratio of women with ovarian cancer (OVCA). To improve early detection, tumor-associated imaging targets need to be established and imaging agents to image these targets need to be developed. Targeted imaging agents offer potential for improvement of signal intensities from their targets. Expression of death receptor 6 (DR6) by ovarian malignant cells and tumor-associated microvessels increases during OVCA development and represents a novel target for ultrasound imaging. The goal of this study was to examine the feasibility of newly developed DR6-targeted ultrasound imaging agents in enhancing early detection of ovarian tumors in laying hen model of spontaneous OVCA. MATERIALS AND METHODS: The study was conducted in an exploratory cross-sectional design using 4-year-old laying hens (n = 130). DR6-targeted imaging agents were developed by conjugating microbubbles with rabbit anti-chicken DR6 antibodies. Changes in signal intensity of ultrasound imaging were determined before and after injection of targeted imaging agents in hens with or without spontaneous OVCA. Following targeted imaging, normal or tumor ovaries were processed for histopathological and immunohistochemical studies. RESULTS: DR6-targeted imaging agents bound with their targets expressed by malignant cells and tumor-associated microvessels in the ovary. Compared with pretargeted imaging, targeted imaging is enhanced by approximately 40% ultrasound echo signal intensity (P < 0.001) from early- and late-stage OVCA. Differences in signal enhancement were not observed among different histological subtypes of OVCA at early or late stages. Higher imaging signal intensities were associated with enhancement in DR6 expression by ovarian malignant cells and increase in the frequency of DR6-expressing microvessels during OVCA development. CONCLUSIONS: The results of this study suggest that DR6-targeted imaging agents enhance the visualization of ovarian tumors and tumor-associated microvessels in hens with early-stage OVCA and will form a foundation for clinical studies.

Number of Ribs Resected is Associated with Respiratory Complications Following Lobectomy with en bloc Chest Wall Resection.

PURPOSE: Pulmonary lobectomy with en bloc chest wall resection is a common strategy for treating lung cancers invading the chest wall. We hypothesized a direct relationship exists between number of ribs resected and postoperative respiratory complications. METHODS: An institutional database was queried for patients with non-small cell lung cancer that underwent lobectomy with en bloc chest wall resection between 2003 and 2014. Propensity matching was used to identify a cohort of patients who underwent lobectomy via thoracotomy without chest wall resection. Patients were propensity matched on age, gender, smoking history, FEV1, and DLCO. The relationship between number of ribs resected and postoperative respiratory complications (bronchoscopy, re-intubation, pneumonia, or tracheostomy) was examined. RESULTS: Sixty-eight patients (34 chest wall resections; 34 without chest wall resection) were divided into 3 cohorts: cohort A = 0 ribs resected (n = 34), cohort B = 1-3 ribs resected (n = 24), and cohort C = 4-6 ribs resected (n = 10). Patient demographics were similar between cohorts. The 90-day mortality rate was 2.9 % (2/68) and did not vary between cohorts. On multivariate analysis, having 1-3 ribs resected (OR 19.29, 95 % CI (1.33, 280.72); p = 0.03), 4-6 ribs resected [OR 26.66, (1.48, 481.86); p = 0.03), and a lower DLCO (OR 0.91, (0.84, 0.99); p = 0.02) were associated with postoperative respiratory complications. CONCLUSIONS: In patients undergoing lobectomy with en bloc chest wall resection for non-small cell lung cancer, the number of ribs resected is directly associated with incidence of postoperative respiratory complications.

The prognostic significance of stable disease following high-dose interleukin-2 (IL-2) treatment in patients with metastatic melanoma and renal cell carcinoma.

High-dose interleukin-2 (HD IL-2) is an approved immunotherapy agent for metastatic melanoma and renal cell carcinoma resulting in objective responses in 15-20 % of patients. An additional subset of patients achieves stable disease, and the natural history of these patients has not been well documented. We hypothesized that stable disease following HD IL-2 is associated with a survival advantage. To explore this hypothesis, a retrospective chart review of 305 patients diagnosed with metastatic melanoma or renal cell carcinoma treated with HD IL-2 was conducted. Patient characteristics, response based on standard RECIST criteria and overall survival were analyzed using the Kaplan-Meier method and associations with clinical response were compared using a log-rank test. Two hundred and forty-five patients had melanoma and 60 had renal cell carcinoma. Of these, 217 had complete data available for analysis. Fifty-nine percentage had progressive disease (PD), 26 % had stable disease (SD) and 15 % had an objective complete (CR) or partial response (PR). Median overall survival was 16.8 months for all patients with available survival data; patients with PD had a median survival of 7.9 months compared to 38.2 months for stable disease, while the median has not been reached for those with objective responses. This retrospective data support an association between overall survival and stable disease, suggesting that clinical benefit may be underestimated for patients treated with HD IL-2. The data further support the use of disease control rate (CR + PR + SD) as a more meaningful endpoint for future clinical studies of tumor immunotherapy, including future studies of HD IL-2.

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics.

Interleukin 16 expression changes in association with ovarian malignant transformation.

OBJECTIVE: Long-term unresolved inflammation has been suggested as a risk factor for the development of various malignancies. The goal of this study was to examine whether the expression of interleukin (IL)-16, a proinflammatory cytokine, changes in association with ovarian cancer (OVCA) development. STUDY DESIGN: In an exploratory study, changes in IL-16 expression in association with OVCA development and progression were determined using ovarian tissues and serum samples from healthy subjects (n = 10) and patients with benign (n = 10) and malignant ovarian tumors at early (n = 8) and late (n = 20) stages. In the prospective study, laying hens, a preclinical model of spontaneous OVCA, were monitored (n = 200) for 45 weeks with serum samples collected at 15-week interval. Changes in serum levels of IL-16 relative to OVCA development were examined. RESULTS: The frequency of IL-16-expressing cells increased significantly in patients with OVCA (P < .001) compared to healthy subjects and patients with benign ovarian tumors. The concentration of serum IL-16 was higher in patients with benign tumors (P < .05) than in healthy subjects and increased further in patients with early-stage (P < .05) and late-stage (P < .03) OVCA. Increase in tissue expression and serum levels of IL-16 in patients with early and late stages of OVCA were positively correlated with the increase in ovarian tumor-associated microvessels. Prospective monitoring showed that serum levels of IL-16 increase significantly (P < .002) even before ovarian tumors become grossly detectable in hens. CONCLUSION: This study showed that tissue expression and serum levels of IL-16 increase in association with malignant ovarian tumor development and progression.

Enhancement of ovarian tumor detection with αvß3 integrin-targeted ultrasound molecular imaging agent in laying hens: a preclinical model of spontaneous ovarian cancer.

OBJECTIVE: Because of the lack of an effective early detection test, ovarian cancer (OVCA) in most cases is detected at late stages and remains a fatal gynecological malignancy. Molecular imaging provides information on the changes associated with the development of a disease at molecular levels. Because angiogenesis is an early event in tumor development, increased expression of αvß3 integrins by ovarian tumor-associated angiogenic microvessels provides a target for noninvasive ultrasound imaging to detect early-stage OVCA. The goal of this study was to examine the feasibility of αvß3 integrin-targeted molecular imaging agent in enhancing the detection of spontaneous ovarian tumor in laying hens, a preclinical model of OVCA. METHODS: The study was conducted in 2 phases, including a cross-sectional exploratory followed by a prospective monitoring of hens for 45 weeks with targeted ultrasound imaging. Changes in ultrasound signal intensity were determined before and after the injection of αvß3 integrin-targeted imaging agent in hens with spontaneous OVCA. All images were digitally stored. After scanning, ovarian tissues from all hens were collected and processed for histopathologic and immunohistochemical studies. RESULTS: Ultrasound signal intensity was significantly (P < 0.001) higher in hens with early-stage OVCA than in normal hens and increased further in late-stage OVCA. Compared with that in normal cases, ultrasound signal intensities increased approximately 19-fold in early stage and 26-fold in late-stage OVCA. Differences in signal enhancement were not observed among different histologic subtypes of OVCA. Higher signal intensities from targeted imaging of ovarian tumors were associated with increased number of αvß3 integrin-expressing ovarian microvessels. Prospective monitoring of hens with αvß3 integrin-targeted imaging agent detected OVCA at early stage. CONCLUSIONS: These results suggest that αvß3 integrin-targeted imaging agent enhanced the visualization of ovarian tumor-associated angiogenic microvessels in hens with early-stage OVCA and may form a foundation for clinical studies.

Magnetic resonance imaging evaluation of normal glenoid length and width: an anatomic study.

PURPOSE: The purpose of this study was to evaluate the measured dimensions of the normal glenoid on sagittal magnetic resonance (MR) imaging to determine whether a fixed ratio of glenoid length and width can be determined. METHODS: MR images of 90 glenoids in 84 patients were analyzed. The mean age was 54.8 years, with 44 male and 40 female patients. Glenoid length and width at the widest dimension were measured and recorded by 3 independent examiners. The ratio of length to width and the ratio of the length of the superior pole at the widest point to the total length were calculated. Intraclass correlation coefficients, Spearman and Pearson correlations, regression analysis with cross validation, and coefficients of variation were calculated. RESULTS: The mean glenoid length was 37.5 ± 3.8 mm, whereas the mean width was 24.4 ± 2.9 mm. The mean ratio of length to width was 1.55 ± 0.1, whereas the mean ratio of the distance from the superior pole to the widest point to the total glenoid length was 0.64 ± 0.03. The calculated ratios were less variable than the absolute length and width. Cross validation of length for width showed a 95% prediction band width of 4.48 mm, with an average absolute error of prediction of 1.46 mm, and was equally specific when separated by gender. The width was equal to 0.65 times the length. CONCLUSIONS: Measurement of glenoid length and width using MR imaging results in a consistent ratio of length to width independent of patient age and gender, where the width was equal to 0.65 times the length at a point two-thirds along the inferosuperior axis. LEVEL OF EVIDENCE: Level IV, case series.