A systematic review showing the lack of diagnostic criteria and tools developed for lower-limb cellulitis

BACKGROUND: Cellulitis can be a difficult diagnosis to make. Furthermore, 31% of patients admitted from the emergency department with suspected lower-limb cellulitis have been misdiagnosed, with incorrect treatment potentially resulting in avoidable hospital admission and the prescription of unnecessary antibiotics. OBJECTIVES: We sought to identify diagnostic criteria or tools that have been developed for lower-limb cellulitis. METHODS: We conducted a systematic review using Ovid MEDLINE and Embase databases in May 2018, with the aim of describing diagnostic criteria and tools developed for lower-limb cellulitis, and we assessed the quality of the studies identified using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We included all types of study that described diagnostic criteria or tools. RESULTS: Eight observational studies were included. Five studies examined biochemical markers, two studies assessed imaging and one study developed a diagnostic decision model. All eight studies were considered to have a high risk for bias in at least one domain. The quantity and quality of available data was low and results could not be pooled owing to the heterogeneity of the findings. CONCLUSIONS: There is a lack of high-quality publications describing criteria or tools for diagnosing lower-limb cellulitis. Future studies using prospective designs, validated in both primary and secondary care settings, are needed. What's already known about this topic? Diagnosing lower-limb cellulitis on first presentation is challenging. Approximately one in three patients admitted from the emergency department with suspected lower-limb cellulitis do not have cellulitis and are given another diagnosis on discharge. Consequently, this results in potentially avoidable hospital admissions and the prescription of unnecessary antibiotics. There are no diagnostic criteria available for lower-limb cellulitis in the U.K. What does this study add? This systematic review has identified a key research gap in the diagnosis of lower-limb cellulitis. There is a current lack of robustly developed and validated diagnostic criteria or tools for use in clinical practice

Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges