Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma.

Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-ß-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.

A systematic review of lateral wedge orthotics--how useful are they in the management of medial compartment osteoarthritis?

Studies on the use of lateral wedge orthotics in the conservative management of medial compartment osteoarthritis are widely quoted. This approach, however, does not consider the disruption of the interaction between lower limb and foot and ankle function that lateral wedges would produce. This comprehensive, systematic review was therefore undertaken to evaluate all available literature to determine whether evidence exists to support their use. MEDLINE, EMBASE, CINAHL, Allied and Complimentary Medicine, PubMed, EBSCO HOST and PEDro, Abstracts of Reviews of Effects in the National Electronic Library for Health for Cochrane Reviews and manual searching were used to identify studies. was searched for trials in progress. Data extraction was performed by the three authors using a paper data extraction form which was based on the CONSORT statement and Critical Skills Appraisal Programme (CASP) guidelines. Overall, the results of this review suggest that, based on current evidence there are no major or long-term beneficial effects with the use of lateral wedges.

Efficacy of an accelerated recovery protocol for Oxford unicompartmental knee arthroplasty--a randomised controlled trial.

Unicompartmental knee arthroplasty (UKA) is appropriate for one in four patients with osteoarthritic knees. This study was performed to compare the safety, effectiveness and economic viability of a new accelerated protocol with current standard care in a state healthcare system. A single blind RCT design was used. Eligible patients were screened for NSAID tolerance, social circumstances and geographical location before allocation to an accelerated recovery group (A) or standard care group (S). Primary outcome was the Oxford Knee Assessment at 6 months post operation, compared using independent Mann-Whitney U-tests. A simple difference in costs incurred was calculated. The study power was sufficient to avoid type 2 errors. Forty-one patients were included. The average stay for Group A was 1.5 days. Group S averaged 4.3 days. No significant difference in outcomes was found between groups. The new protocol achieved cost savings of 27% and significantly reduced hospital bed occupancy. In addition, patient satisfaction was assessed as greater with the accelerated discharge than with the routine discharge time. The strict inclusion criteria meant that 75% of eligible patients were excluded. However, a large percentage of these were due to the distances patients lived from the hospital.

Choosing a home infusion provider.

As the demand for home IV therapy increases, home care agencies must be confident in the quality and standards of the home infusion company they rely on. Having basic criteria to look for when selecting a potential home infusion company can make the task less overwhelming.

Use and abuse of blood cultures: program to limit use.

Many health care providers order an unnecessary number of blood cultures. We studied the ordering habits in our medical intensive care unit and recommended a protocol for appropriate ordering. Implementation of the protocol resulted in a significant reduction in the number of episodes of suspected sepsis, from 39% of patient discharges during the baseline period to 16% during the study period (p = 0.008). The mean number of blood cultures decreased significantly from 1.2 per patient discharge to 0.3 (p = 0.003). The number of episodes when more than four blood cultures were ordered decreased from 7 to 0, resulting in an annual cost savings estimated at $8025. The net benefit was reversed, however, when the protocol ceased to be actively implemented. We concluded that the appropriate ordering of blood cultures can be effected by establishing a protocol that is actively and continuously implemented.

Predicting to 9-month performance of premature infants.

This article identifies variables found to be predictive of sensorimotor and psychosocial performance in infants at 9 months adjusted age. The subjects were 102 infants with a birth weight of less than 1,500 g, who were participants in an early intervention project. Multiple regression analyses disclosed that poor 9-month performance was related to a lack of special Neonatal Intensive Care Unit (NICU) intervention, to minority group membership, to birth weight, and to performance on selected tests administered in the NICU. We present implications for the early prediction of handicapping conditions and for further research.