Immunometabolic Network Interactions of the Kynurenine Pathway in Cutaneous Malignant Melanoma.

Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In this study, plasma from patients diagnosed with metastatic cutaneous malignant melanoma (CMM) was obtained before (PRE) and during treatment (TRM) with inhibitors of mitogen-activated protein kinase pathway (MAPKIs). Immuno-oncology related protein profile and kynurenine metabolites were analyzed by proximity extension assay (PEA) and LC/MS-MS, respectively. Correlation network analyses of the data derived from PEA and LC/MS-MS identified a set of proteins that modulate the differentiation of Th1 cells, which is linked to 3-hydroxykynurenine levels. Moreover, MAPKIs treatments are associated with alteration of 3-hydroxykynurenine and 3hydroxyanthranilic acid (3HAA) concentrations and led to higher "CXCL11," and "KLRD1" expression that are involved in T and NK cells activation. These findings imply that the kynurenine pathway is pathologically relevant in patients with CMM.

The use of the three-point index in the management of extra-articular distal radius fractures.

Conservative management has been the mainstay of treatment for simple extra-articular distal radius fractures. Several factors, such as quality of definitive casting, have been implicated in the risk of fracture re-displacement during follow-up. Objective assessments of the quality of casting using various indices have been documented in literature, although overall evidence remains scant, and only one study in the literature discusses the use of the three-point index (3-PI) in adults. Currently, no independent study assessing the 3-PI in adults has been documented. This retrospective study aimed to assess the 3-PI in terms of (1) predicting fracture re-displacement and (2) evaluating its practicality in everyday clinical use. We had 54 patients (47 female, 7 female), out of which 35 patients had a 3-PI greater than the suggested cutoff value of 0.8; of these, 22 went on to re-displace. The remaining 19 patients had a 3-PI below the cutoff and 14 went on to re-displace. No statistical significance was found for the 3-PI as a predictor for fracture re-displacement, although inter-observer reliability was high; its impact on clinic times (in calculating the 3-PI) remained low.