The Neutrophil-Lymphocyte Ratio and Locoregional Melanoma: A Multicentre Cohort Study

Objectives The neutrophil–lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. Methods This multicentre cohort study describes patients treated for Stage I–III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. Results Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p < 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)]. Conclusion The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma

A multicentre, randomized, double-blind trial of the safety and efficacy of mannose-6-phosphate in patients having Zone II flexor tendon repairs.

The safety, tolerability and preliminary efficacy of mannose 6-phosphate in enhancing the outcome in Zone II flexor tendon repair was studied in a multicentre parallel double-blinded randomized controlled trial. Eight UK teaching hospitals were involved in treating repaired flexor tendons with a single intraoperative intrathecal dose of 600 mM mannose 6-phosphate, with follow-up over 26 weeks. A total of 39 patients (mannose 6-phosphate, n = 20; standard care, n = 19) were randomized. Seven were excluded from the safety and tolerability analysis because of intraoperative findings and eight were excluded due to early dropout ( n = 4) or tendon rupture ( n = 4), leaving 24 (mannose 6-phosphate, n = 13; standard care, n = 11) for assessment of total active motion. The safety, tolerability and other side effects were comparable between the groups. There was no significant difference between the two groups in the total active motion at Week 26. We concluded that mannose 6-phosphate, although safe and tolerable, had no beneficial effect on finger range of motion after Zone II tendon division.Level of evidence 1b</jats:p

Genes encoding candidate pheromone receptors in a moth (Heliothis virescens)

The remarkable responsiveness of male moths to female released pheromones is based on the extremely sensitive and selective reaction of highly specialized sensory cells in the male antennae. These cells are supposed to be equipped with male-specific receptors for pheromonal compounds, however, the nature of these receptors is still elusive. By using a combination of genomic sequence analysis and cDNA-library screening, we have cloned various cDNAs of the tobacco budworm Heliothis virescens encoding candidate olfactory receptors. A comparison of all identified receptor types not only highlighted their overall high degree of sequence diversity but also led to the identification of a small group of receptors sharing >40% identity. In RT-PCR analysis it was found that distinct members of this group were expressed exclusively in the antennae of male moths. In situ hybridization experiments revealed that the male-specific expression of these receptor types was confined to antennal cells located beneath sensillar hair structures (sensilla triochoidea), which have been shown to contain pheromone-sensitive neurons. Moreover, two-color double in situ-hybridization approaches uncovered that cells expressing one of these receptor types were surrounded by cells expressing pheromone-binding proteins, as expected for a pheromone-sensitive sensillum. These findings suggest that receptors like Heliothis receptor 14–16 (HR14–HR16) may render antennal cells responsive to pheromones