Negative-pressure wound therapy (NPWT) plays an important role in the treatment of complex wounds. Its effect on limb salvage in the management of the diabetic foot is well described in the literature. However, a successful outcome in this subgroup of diabetic patients requires a multidisciplinary approach with careful patient selection, appropriate surgical debridement, targeted antibiotic therapy, and optimization of healing markers. Evolving NPWT technology including instillation therapy, nanocrystalline adjuncts, and portable systems can further improve results if used with correct indications. This review article summarizes current knowledge about the role of NPWT in the management of the diabetic foot and its mode of action, clinical applications, and recent developments.

Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. These data provide a mechanistic insight into the paratope−epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. This has important implications for our interpretation of serologic binding patterns of anti-HLA antibodies in sensitized individuals and thus, for the biology of human alloresponses.

Objectives The impact of glucocorticoids on neurocognitive performance in patients with SLE is not fully addressed. We aimed to study the effect of daily and cumulative glucocorticoid dose on neurocognitive performance in SLE patients. Methods Consecutive SLE patients and gender- and age-matched healthy controls (HCs) underwent the computer-based Automated Neuropsychological Assessment Matric (ANAM), which evaluates eight neurocognitive domains including learning, recall, visual perception, mental rotation, short-term memory, attention, sustained attention and working memory. The total and individual-domain throughput scores (TPSs) and the presence of cognitive dysfunction (total TPS <1.5 s.d. below the mean TPS of HCs) were compared between SLE patients and HCs. Within the SLE group, univariate and independent associations between prednisolone dose (daily and cumulative) and individual-domain TPS were studied by univariate and multivariable linear regression, respectively. Results A total of 96 SLE patients and 96 HCs were studied. SLE patients scored significantly worse across all the neurocognitive domains and had a significantly lower mean total TPS (P < 0.001) and a higher prevalence of cognitive dysfunction compared with HCs (25.0 vs 7.3%, P = 0.001). In SLE patients, daily prednisolone dose was significantly and negatively correlated with mathematical-processing TPS, which probes working memory (P = 0.018). No significant correlation between cumulative prednisolone dose and any of the individual-domain TPSs was found. In multivariable regression, higher daily prednisolone dose and doses >9 mg daily remained independently associated with lower mathematical-processing TPSs (P = 0.031). Conclusion Daily prednisolone dose ≥9 mg, but not cumulative glucocorticoid dose, had an independent negative impact on mathematical processing in SLE patients.

The current state-of-the-art technology employed to assess anti-human leukocyte antigen antibodies (Anti-HLA Ab) for donor-recipient matching and patient risk stratification in renal transplantation is the single antigen bead (SAB) assay. However, there are limitations to the SAB assay as it is not quantitative and due to variations in techniques and reagents, there is no standardization across laboratories. In this study, a structurally-defined human monoclonal alloantibody was employed to provide a mechanistic explanation for how fundamental alloantibody biology influences the readout from the SAB assay. Performance of the clinical SAB assay was evaluated by altering Anti-HLA Ab concentration, subclass, and detection reagents. Tests were conducted in parallel by two internationally accredited laboratories using standardized protocols and reagents. We show that alloantibody concentration, subclass, laboratory-specific detection devices, subclass-specific detection reagents all contribute to a significant degree of variation in the readout. We report a significant prozone effect affecting HLA alleles that are bound strongly by the test alloantibody as opposed to those bound weakly and this phenomenon is independent of complement. These data highlight the importance for establishing international standards for SAB assay calibration and have significant implications for our understanding of discordance in previous studies that have analyzed its clinical relevance.