BackgroundInflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers.MethodsNineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data.ResultsCompared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (−0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells.ConclusionWe present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.

The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cellApproximately 70% of individuals in developed societies suffer from low back pain (LBP) and neck pain at some point 1, 2 . The socioeconomic impact of LBP amounts to over £12 billion in the UK alone 3 , and whilst the underlying pathologies of these are multifactorial, degeneration of the lumbar and cervical intervertebral discs (IVDs) have been directly correlated to the development of these conditions 4,5 . Degeneration of the IVD is a progressive age-related disorder. Symptomatic relief may be achieved utilising current therapeutic strategies; however such strategies fail to address the underlying pathogenesis and aberrant cell biology and thus are ineffective for long-term treatment of this disease. The research community therefore continues to strive to improve understanding of the cellular and molecular biology of the healthy and degenerate disc in order to inform development of novel regenerative strategies.In order for effective regenerative strategies to be developed, it is essential that the phenotype of cells intended for recapitulation is fully elucidated. Cells of the adult human NP have routinely been likened to articular chondrocyte (AC) cells, with regards to both phenotype and morphology 6 . However, clear distinctions in the ECM produced by AC and NP cells have been demonstrated 7 , which has implications for the hydration state and

BackgroundSurgical site infections (SSIs) are wound infections that occur after an operative procedure. A preventable complication, they are costly and associated with poorer patient outcomes, increased mortality, morbidity and reoperation rates. Surgical wound irrigation is an intraoperative technique, which may reduce the rate of SSIs through removal of dead or damaged tissue, metabolic waste, and wound exudate. Irrigation can be undertaken prior to wound closure or postoperatively. Intracavity lavage is a similar technique used in operations that expose a bodily cavity; such as procedures on the abdominal cavity and during joint replacement surgery.ObjectivesTo assess the effects of wound irrigation and intracavity lavage on the prevention of surgical site infection (SSI).Search methodsIn February 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched three clinical trials registries and references of included studies and relevant systematic reviews. There were no restrictions on language, date of publication or study setting.Selection criteriaWe included all randomised controlled trials (RCTs) of participants undergoing surgical procedures in which the use of a particular type of intraoperative washout (irrigation or lavage) was the only systematic difference between groups, and in which wounds underwent primary closure. The primary outcomes were SSI and wound dehiscence. Secondary outcomes were mortality, use of systemic antibiotics, antibiotic resistance, adverse events, re-intervention, length of hospital stay, and readmissions.Data collection and analysisTwo review authors independently assessed studies for inclusion at each stage. Two review authors also undertook data extraction, assessment of risk of bias and GRADE assessment. We calculated risk ratios or differences in means with 95% confidence intervals where possible.Main resultsWe included 59 RCTs with 14,738 participants. Studies assessed comparisons between irrigation and no irrigation, between antibacterial and non-antibacterial irrigation, between different antibiotics, different antiseptics or different non-antibacterial agents, or between different methods of irrigation delivery. No studies compared antiseptic with antibiotic irrigation.Surgical site infectionIrrigation compared with no irrigation (20 studies; 7192 participants): there is no clear difference in risk of SSI between irrigation and no irrigation (RR 0.87, 95% CI 0.68 to 1.11; I2 = 28%; 14 studies, 6106 participants). This would represent an absolute difference of 13 fewer SSIs per 1000 people treated with irrigation compared with no irrigation; the 95% CI spanned from 31 fewer to 10 more SSIs. This was low-certainty evidence downgraded for risk of bias and imprecision.Antibacterial irrigation compared with non-antibacterial irrigation (36 studies, 6163 participants): there may be a lower incidence of SSI in participants treated with antibacterial ir...