Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.

Percutaneous Image-Guided Cryoablation of Musculoskeletal Metastases: Pain Palliation and Local Tumor Control.

PURPOSE: To evaluate the safety and effectiveness of cryoablation of musculoskeletal metastases in terms of achieving pain palliation and local tumor control. MATERIALS AND METHODS: A retrospective review was performed of 92 musculoskeletal metastases in 56 patients treated with percutaneous image-guided cryoablation. Mean age of the cohort was 53.9 y ± 15.1, and cohort included 48% (27/56) men. Median tumor volume was 13.0 cm3 (range, 0.5-577.2 cm3). Indications for treatment included pain palliation (41%; 38/92), local tumor control (15%; 14/92), or both (43%; 40/92). Concurrent cementoplasty was performed after 28% (26/92) of treatments. RESULTS: In 78 tumors treated for pain palliation, median pain score before treatment was 8.0. Decreased median pain scores were reported 1 day (6.0; P < .001, n = 62), 1 week (5.0; P < .001, n = 70), 1 month (5.0; P < .001, n = 63), and 3 months (4.5; P = .01, n = 28) after treatment. The median pain score at 6-month follow-up was 7.5 (P = .33, n = 11). Radiographic local tumor control rates were 90% (37/41) at 3 months, 86% (32/37) at 6 months, and 79% (26/33) at 12 months after treatment. The procedural complication rate was 4.3% (4/92). The 3 major complications included 2 cases of hemothorax and 1 transient foot drop. CONCLUSIONS: Cryoablation is an effective treatment for palliating painful musculoskeletal metastases and achieving local tumor control.

Primary vascularization of allografts governs their immunogenicity and susceptibility to tolerogenesis.

We investigated the influence of allograft primary vascularization on alloimmunity, rejection, and tolerance in mice. First, we showed that fully allogeneic primarily vascularized and conventional skin transplants were rejected at the same pace. Remarkably, however, short-term treatment of mice with anti-CD40L Abs achieved long-term survival of vascularized skin and cardiac transplants but not conventional skin grafts. Nonvascularized skin transplants triggered vigorous direct and indirect proinflammatory type 1 T cell responses (IL-2 and IFN-γ), whereas primarily vascularized skin allografts failed to trigger a significant indirect alloresponse. A similar lack of indirect alloreactivity was also observed after placement of different vascularized organ transplants, including hearts and kidneys, whereas hearts placed under the skin (nonvascularized) triggered potent indirect alloresponses. Altogether, these results suggest that primary vascularization of allografts is associated with a lack of indirect T cell alloreactivity. Finally, we show that long-term survival of vascularized skin allografts induced by anti-CD40L Abs was associated with a combined lack of indirect alloresponse and a shift of the direct alloresponse toward a type 2 cytokine (IL-4, IL-10)-secretion pattern but no activation/expansion of Foxp3(+) regulatory T cells. Therefore, primary vascularization of allografts governs their immunogenicity and tolerogenicity.

Evaluation of medical student experience using medical student created StudentPACS flash based PACS simulator tutorials for learning radiological topics.

RATIONALE AND OBJECTIVES: With studies regularly containing hundreds of images, the authors believe that the ability to efficiently review numerous images and identify findings is an important skill to teach medical students. Using the StudentPACS Adobe Flash extension, created within their department, the authors created StudentPACS modules that provide users with a virtual picture archiving and communication system environment, in which findings can be selected by mouse, triggering questions with referenced answers. The aim was to assess medical students' impressions of how learning from these modules compared to their personal experiences learning radiology from textbooks or static images. MATERIALS AND METHODS: StudentPACS modules were created by medical students on elective under the supervision of resident and attending radiologists. MS I to IV students were then asked to complete StudentPACS modules that tied in with their current coursework, followed by an anonymous survey. Approximately 293 students participated. RESULTS: The majority of students reported that StudentPACS modules were either equivalent to or better than learning from static images or textbooks (90 +/- 3% [257 of 285], P < .00002), were not difficult to use (85 +/- 4% [248 of 293], P < .00002), presented them with clinical content that tied in well with the depicted imaging (90 +/- 3% [263 of 293], P < .00002), and taught them new information (69 +/- 5% [202 of 293], P < .00002). Most respondents felt the StudentPACS modules presented information they would find useful in clinical practice (91 +/- 3% [266 of 293], P < .00002), reported satisfactory experiences using StudentPACS modules as a source of self-directed learning material (79 +/- 5% [232 of 293], P < .00002), and stated that they would use StudentPACS modules for learning different topics in the future (85.6 +/- 4% [244 of 285], P < .00002). CONCLUSION: Medical students found using StudentPACS modules at least equivalent to, if not better than, using static books or annotated images.