Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Improved speech and language development after unilateral cochlear implantation in children with a potentially useable contralateral ear.

OBJECTIVES: Increasingly, children are considered for a unilateral cochlear implant (CI), even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. Here we present the outcomes of CI in children with potentially useable hearing in the contralateral ear. METHODS: A retrospective case note review was performed for a total of 57 patients. Primary outcome was speech and language (SaL) development, as measured by the Manchester Speech and Language Development Scale (MSLDS) and SaL age equivalent. Secondary outcomes were auditory perception, perceived parental benefit and compliance; respectively measured by Categories of Auditory Performance (CAP), Brief Assessment of Parental Perception (BAPP) and reported use. RESULTS: SaL development improved after CI with a mean pre-operative MSLDS score of 5.8 to a postoperative score of 8.0 (n = 57) and a mean SaL age equivalent of 14 months in a one-year period (n = 14). Furthermore, CAP scores improved from 4.9 to 7.0 (n = 57). Analysis of BAPP scores showed improved quality of life in 18/19 patients (94.7%). With regards to compliance, 50/57 (87.7%) are fulltime users of both their CI and their HA. CONCLUSION: The present study indicates that despite one ear having potentially useable hearing outside national audiological criteria, the majority of participants received benefit from a CI in the poorer hearing ear. We suggest that assessment of each ear separately and treatment with the most appropriate amplification device, has given these children a benefit they may not otherwise have acquired if they only had bilateral HA.

IFN-γ synergistically enhances LPS signalling in alveolar macrophages from COPD patients and controls by corticosteroid-resistant STAT1 activation.

BACKGROUND AND PURPOSE: IFN-γ levels are increased in chronic obstructive airway disease (COPD) patients compared with healthy subjects and are further elevated during viral exacerbations. IFN-γ can 'prime' macrophages to enhance the response to toll-like receptor (TLR) ligands, such as LPS. The aim of this study was to examine the effect IFN-γ on corticosteroid sensitivity in alveolar macrophages (AM). EXPERIMENTAL APPROACH: AM from non-smokers, smokers and COPD patients were stimulated with IFN-γ and/or LPS with or without dexamethasone. IL-6, TNF-α and IFN-γ-induced protein 10 kDa (IP-10) levels were measured by elisa, and Western blots were used to investigate the IFN-γ-stimulated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway. Real-time PCR and flow cytometry were used to investigate TLR levels following IFN-γ treatment. KEY RESULTS: In all three subject groups, IFN-γ alone had no effect on IL-6 and TNF-α production but enhanced the effects of LPS on these cytokines. In contrast, IFN-γ alone increased the production of IP-10. IFN-γ increased TLR2 and TLR4 expression in AM. Cytokine induction and STAT1 activation by IFN-γ were insensitive to dexamethasone for all groups. The inhibition of JAK and STAT1 repressed all these IFN-γ effects. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that IFN-γ-induced STAT-1 signalling is corticosteroid resistant in AMs, and that targeting IFN-γ signalling by JAK inhibitors is a potentially novel anti-inflammatory strategy in COPD.