T cells are crucial for the control of cytomegalovirus (CMV) in infected individuals. Although CMV-specific T cells can be quantified by various methods, clear correlates of protection from CMV disease have not been defined. However, responses to the pp65 protein are believed to play an important role. Here, the proportions of interferon γ–producing T cells following ex vivo activation with pools of overlapping peptides representing the pp65 and immediate early (IE)-1 proteins were determined at multiple time points and related to the development of CMV disease in 27 heart and lung transplant recipients. Frequencies of IE-1–specific CD8 T cells above 0.2 and 0.4% at day 0 and 2 wk, respectively, or 0.4% at any time during the first months discriminated patients who did not develop CMV disease from patients at risk, 50–60% of whom developed CMV disease. No similar distinction between risk groups was possible based on pp65-specific CD8 or CD4 T cell responses. Remarkably, CMV disease developed exclusively in patients with a dominant pp65-specific CD8 T cell response. In conclusion, high frequencies of IE-1 but not pp65-specific CD8 T cells correlate with protection from CMV disease. These results have important implications for monitoring T cell responses, adoptive cell therapy, and vaccine design.

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Abstract. integrins mediate the interaction of cells with the extracellular matrix and are believed to be involved in tumor cell survival and metastasis, and in tumor angiogenesis. We used immunohistochemistry of fresh-frozen human tumor tissues to analyze the presence of integrins αvβ3, αvβ5 and α5β1, which are believed to be involved in tumor growth and migration, together with integrin ligands, vitronectin, osteopontin, fibronectin and fibrinogen, in human oral squamous cell carcinomas. Samples of squamous cell carcinomas and control tissues from patients without cancer undergoing oral or maxillofacial surgery were frozen in liquid nitrogen within 30 min of removal. Frozen sections were prepared, and the presence of integrins or ligands was visualized using standard immunohistochemistry (apaap) with a blinded evaluation. comparison of samples from the 40 oral cancer patients and the 20 controls revealed increased staining in tumors compared with the controls, and staining was demonstrated for αvβ3 in endothelia. αvβ5 staining was increased in the tumor samples, but this was associated with increased expression in stroma rather than in endothelia. modestly increased expression of α5β1 was observed in the tumor samples, and this was associated with tumor cells, endothelia and stroma. Expression of ligands for the integrins varied between tissue types, with increased fibrinogen and fibronectin expression in tumor endothelia. Confirmation of the presence of these integrins and their association with tumor cells, endothelia or stroma suggests their potential for these integrins in human oral tumors. Overall, the increased expression of integrins within tumors, particularly expression associated with endothelial cells, supports the principle of selective integrin blockade as a novel anticancer strategy. IntroductionWorldwide, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (HNSCC) has not significantly increased for many years (1-5). HNSCC is diagnosed predominantly at the age range of 50-70 years, but is also observed in younger patients (6-8). despite aggressive initial management of the primary tumor, locoregional recurrence occurs in some 60% of cases, and distant metastasis is observed in some 25%. therefore, innovative therapeutic concepts are urgently required.angiogenesis is essential for tumor progression and metastasis. tumor angiogenesis is complex and involves crosstalk between tumor-derived growth factors, the modified extracellular matrix that develops around tumors, and endothelial receptors for extracellular matrix and growth factors (9,10). inhibition of angiogenesis often suppresses the tumor growth of model tumors, and the suppression and eradication of malignant tumors by targeting angiogenetic endothelial cells is a rapidly evolving approach to cancer therapy (10,11

BackgroundWithin the domain of craniomaxillofacial surgery, orthognathic surgery is a special field dedicated to the correction of dentofacial anomalies resulting from skeletal malocclusion. Generally, in such cases, an interdisciplinary orthodontic and surgical treatment approach is required. After initial orthodontic alignment of the dental arches, skeletal discrepancies of the jaws can be corrected by distinct surgical strategies and procedures in order to achieve correct occlusal relations, as well as facial balance and harmony within individualized treatment concepts. To transfer the preoperative surgical planning and reposition the mobilized dental arches with optimal occlusal relations, surgical splints are typically used. For this purpose, different strategies have been described which use one or more splints. Traditionally, these splints are manufactured by a dental technician based on patient-specific dental casts; however, computer-assisted technologies have gained increasing importance with respect to preoperative planning and its subsequent surgical transfer.Methods: In a pilot study of 10 patients undergoing orthognathic corrections by a one-splint strategy, two final occlusal splints were produced for each patient and compared with respect to their clinical usability. One splint was manufactured in the traditional way by a dental technician according to the preoperative surgical planning. After performing a CBCT scan of the patient’s dental casts, a second splint was designed virtually by an engineer and surgeon working together, according to the desired final occlusion. For this purpose, RapidSplint®, a custom-made software platform, was used. After post-processing and conversion of the datasets into .stl files, the splints were fabricated by the PolyJet procedure using photo polymerization. During surgery, both splints were inserted after mobilization of the dental arches then compared with respect to their clinical usability according to the occlusal fitting.ResultsUsing the workflow described above, virtual splints could be designed and manufactured for all patients in this pilot study. Eight of 10 virtual splints could be used clinically to achieve and maintain final occlusion after orthognathic surgery. In two cases virtual splints were not usable due to insufficient occlusal fitting, and even two of the traditional splints were not clinically usable. In five patients where both types of splints were available, their occlusal fitting was assessed as being equivalent, and in one case the virtual splint showed even better occlusal fitting than the traditional splint. In one case where no traditional splint was available, the virtual splint proved to be helpful in achieving the final occlusion.ConclusionsIn this pilot study it was demonstrated that clinically usable splints for orthognathic surgery can be produced by computer-assisted technology. Virtual splint design was realized by RapidSplint®, an in-house software platform which might contribute in future to shorten preoperative workflows fo...