Oncolytic measles viruses encoding interferon β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

Mesothelioma usually leads to death within 8–14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon β (IFNβ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNβ (mIFNβ) viruses, MV-mIFNβ and MV-mIFNβ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNβ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNβ-NIS. MV with mIFNβ expression triggered CD68-positive immune cell infiltration 2–4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNβ or MV-mIFNβ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNβ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNβ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNβ and NIS will be potent and versatile agents for the treatment of human mesothelioma

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Remove, rotate, and reimplant: a novel technique for the management of exposed porous anophthalmic implants in eviscerated patients

PURPOSE: To describe and to evaluate a new and relatively easy technique for porous implant exposure repair. METHODS: Eleven patients with exposed porous orbital implants after evisceration were included in this study. Five patients with large exposures (diameter>7 mm) and six patients with small exposures of orbital implants (diameter<7 mm) that persisted despite posterior vaulting of the prosthesis and usage of antibiotics and steroids for more than 6 weeks, underwent revision surgery with the remove-rotate-reimplant technique (3R technique). Negative microbiological culture taken from the exposed socket surface before surgery was the major inclusion criterion. Five patients with insufficient conjunctival tissue also underwent additional mucosa or hard palate grafting of the defect in addition to the remove-rotate-reimplant procedure. RESULTS: Patients have been followed up for more than 18 months (ranging from 18–30 months). None of them received motility peg insertion after repair. Implant reexposure was detected in one patient during the follow-up period, which was managed by dermis fat grafting with implant removal. CONCLUSION: The remove-rotate-reimplant technique is an effective surgical method for repairing exposed porous anophthalmic implants after evisceration with a 90% success in this study. It avoids the removal of the implant from the sclera, which is a traumatic procedure that may lead to the tearing and loss of scleral tissue covering the implant. Saving the porous implant and scleral cover reduces the surgical time and cost

Orbital Implants and Wrapping Materials

Following globe removal, the surgeon must determine the best orbital implant to place into the anophthalmic socket. A decision on appropriate implant size, whether to place a porous or nonporous implant, and a patient’s total clinical picture must be considered to prevent future complications. Other considerations, including whether to wrap an implant and place a motility peg, must also be made. The modern implant is built on the foundation of anophthalmic socket reconstruction—implant retention, volume replacement, and adequate prosthetic motility. This chapter will review the special considerations the ophthalmic surgeon must weigh when choosing an orbital implant following enucleation and evisceration surgeries