Outcomes and Prognosis of Neurological Decompression and Stabilization for Spinal Metastasis: Is Assessment with the Spinal Instability Neoplastic Score Useful for Predicting Surgical Results?

Study Design Retrospective study. Purpose To evaluate the efficacy of the Spinal Instability Neoplastic Score (SINS) in predicting surgical outcomes and survival. Patients were categorized into two groups according to the SINS, and their surgical outcomes and survival following decompression and stabilization were assessed. Overview of Literature Palliative surgery in patients with a life expectancy ≥3 months may effectively improve their overall condition in the long term. Currently, the effectiveness of the SINS for predicting surgical results and survival remains controversial. Methods This study included 44 patients who underwent decompression and stabilization for spinal metastases at Yokosuka Kyosai Hospital between 2008 and 2017. The patients were divided into two groups: stable (SINS ≤12) and unstable (SINS ≥13). Changes in the Frankel score and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were compared between the two groups, and patient survival was evaluated according to the SINS, Tokuhashi score, and Katagiri score. Results The stable group (SINS range, 7–12) included 24 patients while the unstable group (SINS range, 13–16) included 20 patients. The Frankel score significantly improved from 2.8 to 3.6 in the stable group (p <0.001) and from 2.7 to 3.9 in the unstable group (p <0.001). The ECOG-PS significantly improved from 3.2 to 2.1 in the stable group (p <0.001) and from 3.0 to 1.8 in the unstable group (p <0.001). There was a statistically significant difference in median survival between the two groups. Conclusions All patients treated with palliative surgery showed favorable outcomes, as indicated by improved the Frankel score and ECOG-PS following surgery. However, median survival was significantly better in the stable group. The results of this study indicate that the SINS is appropriate for surgical decision making and may be used to predict survival

Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease

Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and wound healing in the skin after SCT. Topical corticosteroids, a standard of care for a wide range of skin disorders including GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti-inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+ HFSCs and that topical ruxolitinib represents a novel strategy to protect skin stem cells and maintain skin homeostasis in GVHD

R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease

The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota cross talk toward therapeutic benefits