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Three-dimensional porous scaffolds prepared from regenerated silk fibroin using either an all aqueous process or a process involving an organic solvent, hexafluoroisopropanol (HFIP) have shown promise in cell culture and tissue engineering applications. However, their biocompatibility and in vivo degradation has not been fully established. The present study was conducted to systematically investigate how processing method (aqueous vs. organic solvent) and processing variables (silk fibroin concentration and pore size) affect the short-term (up to 2 months) and longterm (up to 1 year) in vivo behavior of the protein scaffolds in both nude and Lewis rats. The samples were analyzed by histology for scaffold morphological changes and tissue ingrowth, and by real-time RT-PCR and immunohistochemistry for immune responses. Throughout the period of implantation, all scaffolds were well-tolerated by the host animals and immune responses to the implants were mild. Most scaffolds prepared from the all aqueous process degraded to completion between two and six months, while those prepared from organic solvent (hexafluoroisopropanol (HFIP)) process persisted beyond one year. Due to widespread cellular invasion throughout the scaffold, the degradation of aqueous-derived scaffolds appears to be more homogeneous than that of HFIP-derived scaffolds. In general and especially for the HFIP-derived scaffolds, a higher original silk fibroin concentration (e.g. 17%) and smaller pore size (e.g. 100-200 µm) resulted in lower levels of tissue ingrowth and slower degradation. These results demonstrate that the in vivo behavior of the three-dimensional silk fibroin scaffolds is related to the morphological and structural features that resulted from different scaffold preparation processes. The insights gained in this study can serve as a guide for processing scenarios to match desired morphological and structural features and degradation time with tissue-specific applications.

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MR imaging-guided focused ultrasound surgery results in symptomatic improvement, sustained to 12 months after treatment. Treatment with a modified protocol results in greater clinical effectiveness and fewer AEs.

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OBJECTIVES: The aims of this prospective study were to document the incidence of colon immediate postpolypectomy bleeding (IPPB) according to grade, and to identify potential risk factors of IPPB in patients who have received complete colonoscopy and polypectomy because of a colorectal polyp. METHODS:This was a prospective, cross-sectional study of 5,152 patients treated at 11 tertiary medical centers between July 2003 and July 2004. Patient-related, polyp-related, and procedure-related variables were evaluated as potential risk factors for IPPB. IPPB was defined as a bleeding occurring during the procedure and was graded as G1-G4. Risk factors associated with IPPB were analyzed by univariate and multivariate logistic regression analysis. RESULTS:A total of 9,336 colonic polyps were removed in 5,152 patients, and 262 (2.8%) colorectal polyps in 215 patients presented with IPPB. Polyp-based multivariate analysis revealed that old age (≥65 yr), comorbid cardiovascular or chronic renal disease, anticoagulant use, polyp size greater than 1 cm, gross morphology of polyps such as pedunculated polyp or laterally spreading tumor, poorer bowel preparation, cutting mode of the electrosurgical current, and the inadvertent cutting of a polyp before current application were significant risk factors for IPPB.CONCLUSION: Nine factors have been found to be associated with IPPB and polypectomy should be undertaken with caution under these conditions.

BackgroundImmunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.Main bodyThe ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells’ niche as well as impart distant effects on remote cells with a similar molecular profile.ConclusionIt is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.