Advanced Cell Mapping Visualizations for Single Cell Functional Proteomics Enabling Patient Stratification.

Highly multiplexed single-cell functional proteomics has emerged as one of the next-generation toolkits for a deeper understanding of functional heterogeneity in cell. Different from the conventional population-based bulk and single-cell RNA-Seq assays, the microchip-based proteomics at the single-cell resolution enables a unique identification of highly polyfunctional cell subsets that co-secrete many proteins from live single cells and most importantly correlate with patient response to a therapy. The 32-plex IsoCode chip technology has defined a polyfunctional strength index (PSI) of pre-infusion anti-CD19 chimeric antigen receptor (CAR)-T products, that is significantly associated with patient response to the CAR-T cell therapy. To complement the clinical relevance of the PSI, a comprehensive visualization toolkit of 3D uniform manifold approximation and projection (UMAP) and t-distributed stochastic neighbor embedding (t-SNE) in a proteomic analysis pipeline is developed, providing more advanced analytical algorithms for more intuitive data visualizations. The UMAP and t-SNE of anti-CD19 CAR-T products reveal distinct cytokine profiles between nonresponders and responders and demonstrate a marked upregulation of antitumor-associated cytokine signatures in CAR-T cells from responding patients. Using this powerful while user-friendly analytical tool, the multi-dimensional single-cell data can be dissected from complex immune responses and uncover underlying mechanisms, which can promote correlative biomarker discovery, improved bioprocessing, and personalized treatment development.

The effect of total knee arthroplasty on lower limb blood flow.

Acute arterial injury at the time of total knee replacement (TKR) is a rare occurrence. We questioned whether TKR could exacerbate preexisting atherosclerotic disease causing chronic limb ischemia. Thirty-three patients undergoing unilateral TKR had the peripheral arterial supply of both legs assessed 2 weeks before and 6 weeks after the operation using various methods. Although a statistically significant reduction in the velocity ratio was measured in the trial leg, 0.92 (0.33) as compared to the control, 1.11 (0.46) (P = .0002) this was not found to be clinically significant when the minimum popliteal artery diameter of the trial limb, 6.23 (1.32), was compared with the control, 6.28 (1.27) (P = .8246). Neither were significant reductions in arterial waveforms or ABPIs measured in the trial legs preoperatively, 0.97 (0.20), and postoperatively, 0.93 (0.27) (P = .2793). TKR does not impair the arterial supply of the limb at 6-week postoperative period.

The use of collagen injections in the treatment of metatarsalgia: a case report.

Metatarsalgia is an increasingly common condition seen in the outpatient setting. A number of conservative and surgical management options are available for this condition. We present an interesting case that was unsuccessfully treated with'dermal filler.' To our knowledge, we have not found any published material in peer-reviewed journals documenting the use of collagen injections in the treatment of metatarsalgia. The authors feel that the lesson learned from this case should be highlighted for other foot and ankle surgeons.