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Supplementary Materials, Methods, Figures and Table legends - PDF file 87K, Supplementary file giving details of supplementary materials and methods, figure legends and table legends

Supplementary Figure S2 - PDF file 84K, Phenotype of DCs following lysate-pulsing (i.e. HOCl-L, UVB-L or FTL), and activation with LPS and IFN-gamma. Unpulsed, mature (mDC) or immature DCs (iDC) served as controls. Data was presented as mean plus-minus SEM

Supplementary Table S1 - PDF file 191K, Cytokine and chemokine productions from DCs of ovarian cancer subjects that were loaded with HOCl-oxidized autologous whole tumor lysate and matured with LPS and IFN-gamma

Purpose: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells.Experimental Design: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo.Results: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate–pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC.Conclusions: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801–15. ©2013 AACR.

T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients' prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8

T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients’ prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.

To assess the radiology department chairs' opinions concerning current status and plans for teaching ultrasound to medical students, the American College Taskforce on Radiology Ultrasound Education, commissioned by the American College of Radiology, distributed a survey to 142 radiology chairs and a medical school dean subgroup.The response rate was 30% (42/142), and 76% indicated ultrasound was currently part of the medical student curriculum. In preclinical years, radiology involvement was only 6.4%. During clinical years, radiology led ultrasound education with 51.7% in general and 82.9% in elective rotations. Regarding actual content, top 4 results were evenly distributed between learning hands-on scanning (81.1%), diagnostic use of ultrasound (75.7%), anatomy/pathology (75.7%), and ultrasound guidance for procedures (54.0%). Educational leaders in preclinical courses were emergency medicine (72.7%) followed by radiology (45.4%) physicians. During clinical years, leaders were radiology (52.6%) and emergency medicine (47.4%) physicians. Most chairs stated that knowledge of diagnostic ultrasound should be mandatory (76.2%), stressing the importance of teaching the diagnostic capabilities and uses of ultrasound as the primary goal (78.8%). Perceived barriers to implementation were evenly distributed between lack of space in the curriculum (55.6%), lack of faculty (48.2%), lack of resources (44.4%), and lack of institutional support (40.7%). The American College Taskforce on Radiology Ultrasound Education survey shows that radiology's role in ultrasound undergraduate education occurs almost exclusively during clinical years, and the chairs voice a desire to improve upon this role. Barriers include both intradepartmental (faculty and resources) and institutional (curricular) factors.

The 2016 RAD-AID Conference analyzed the accelerated global activity in the radiology community that is transforming medical imaging into an effective spearhead of health care capacity building in low- and middle-income countries. Global health efforts historically emphasized disaster response, crisis zones, and infectious disease outbreaks. However, the projected doubling of cancer and cardiovascular deaths in developing countries in the next 15 years and the need for higher technology screening and diagnostic technologies in low-resource regions, as articulated by the United Nations' new Sustainable Development Goals of 2016, is heightening the role of radiology in global health. Academic US-based radiology programs with RAD-AID chapters achieved a threefold increase in global health project offerings for trainees in the past 5 years. RAD-AID's nonprofit radiology volunteer corps continue to grow by more than 40% yearly, with a volunteer base of 5,750 radiology professionals, serving in 23 countries, donating close to 20,000 pro bono hours globally in 2016. As a high-technology specialty interfacing with nearly all medical and surgical disciplines, radiology underpins vital health technology infrastructure, such as digital imaging archives, electronic medical records, and advanced diagnosis and treatment, essential for long-term future health care capacity in underserved areas of the world.

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naive, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.

Purpose The purpose of this work was to determine the costs of computed tomography (CT) procedures in a large academic radiology department, including both professional (PC) and technical (TC) components, by analyzing actual resource consumption using an activity-based costing (ABC) method and comparing them with Medicare payments. Method Over a 12 month period from July 1, 1996, to June 30, 1997, 1,011 CT procedures, representing 16 Physicians' Current Procedural Terminology (CPT) codes and 98.3% of CT studies performed, were carefully observed by a research assistant trained in ABC methodology. Information collected during these time and motion studies included personnel/machine time and direct materials used. Actual resource units used during the different activities in each CT procedure were valued using appropriate cost drivers. Unit values for both direct and overhead costs were calculated: the cost of an individual procedure equaled the sum of component costs. Costs were compared with PC and TC payments according to the 1997 Medicare Fee Schedule. Results Total costs of CPT codes 70450 (CT Head unenhanced), 71260 (CT Chest enhanced), and 74160 (CT Abdomen enhanced), which represented 71.2% of CT studies performed, were $189.19, $273.53, and $343.20, respectively. For all 16 nonmodified CPT codes analyzed, Medicare's professional reimbursement was less than the professional cost, whereas its technical reimbursement exceeded respective cost in 14 of the 16 codes. Conclusion In the setting and time period studied, Medicare underreimbursed professional costs while overreimbursing technical costs.

Hepatic sonography is useful in characterizing many focal liver lesions (Tables 2-6). It is safe, portable, and relatively inexpensive. With the development of color Doppler imaging, power Doppler imaging, and intravenous-ultrasound contrast agents, the ability to detect and precisely diagnose a focal hepatic lesion may be improved.

Background Bow hunter's syndrome refers to symptomatic vertebrobasilar insufficiency provoked by physiologic head rotation. Case Description We report a unique case of bow hunter's syndrome caused by an accessory cervical ossification and the first use of intraoperative Doppler ultrasonography directly upon the vertebral artery during the surgical repair. After a traumatic motor-vehicle collision, the patient developed recurrent syncopal episodes when he turned his head abruptly to the right. Transcranial Doppler studies and vertebral angiography with the patient's neck rotated into the symptomatic position revealed marked reduction of vertebral artery flow, and fine-cut CT of the upper cervical spine demonstrated the compressive accessory ossicle. Intraoperative Doppler ultrasound performed with the head in neutral and rotated positions, before and after surgical decompression, demonstrated restoration of blood flow in the vertebral artery. We discuss the mechanisms of bow hunter's syndrome and the advantages of intraoperative Doppler ultrasonography. Conclusion This case describes the first use of intraoperative Doppler ultrasonography directly upon the vertebral artery to provide an unrestricted real-time assessment of the surgical decompression for bow hunter's syndrome.

A case is reported of congenital cytomegalovirus infection. A baby girl was born at an estimated gestational age of 35 weeks to a 26-year-old Hispanic women. There was maternal cocaine abuse and poor prenatal care, and variable decelerations, abruptio placentae, and meconium-stained fluid occurred in the intrapartum period. Cytomegalovirus was isolated from the urine, with growth occurring in 48 hours, and the neonate had characteristic neurodevelopment handicaps.