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Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
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Abstract – Traumatic dental injuries often occur to the teeth and their supporting tissues and they are the main reasons for emergency visit to a dental clinic. Management of a fracture depends on its position and the extent of root involvement. Horizontal root fractures are not seen frequently and the treatment consists of reduction and long‐term rigid fixation of the coronal segment. The present case demonstrates the successful management of two horizontally fractured maxillary central incisors with a follow‐up period of 9 months. 相似文献
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Autotransplantation of splenic tissue 总被引:4,自引:0,他引:4
Autotransplantation of splenic fragments has already been carried out in humans. The optimal size of the particles and amount of tissue required for this procedure has yet to be found. In normal young pigs and miniature piglets, autologous splenic tissue was transplanted into the greater omentum. The regenerated splenic mass, splenic blood flow, and histology were studied six months later. Implanting small splenic particles produced comparable results to implanting thin slices of splenic tissue. The mass of regenerated splenic tissue was only 3.1 g after implanting the whole spleen and 4.5 g after transplanting half of the spleen, which means 5.3% and 7.8% respectively of the weight of control spleens. The blood flow per gram in the regenerated splenic tissue was much lower than in the normal spleen. The blood flow in the whole of the splenic tissue is important for the clearance function of the spleen. Six months after transplanting the whole or half of the spleen, the blood flow to the regenerated splenic tissue was only 1% of that in the control minipigs. When half of the spleen was left in situ, as a model for a partial splenectomy, and the other half transplanted, the regenerated mass was only 3.4% of all splenic tissue and the blood flow 1.5% of the total splenic blood flow. In this model the regenerated splenic mass was independent of the size of the implants and the mass of implanted tissue. The extremely low blood flow indicates an inadequate clearance function and thus the protective function would probably be negligible. 相似文献
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Kamran Ahmed Ashok Kelshiker Christopher Jenner 《Primary care respiratory journal》2007,16(4):249-251
AIMS AND OBJECTIVES: To screen for, and to treat, depression in COPD patients in a general practice surgery, and to test the feasibility of the screening method. METHODS: We sent The Beck Depression Inventory (BDI) Short-Form Questionnaire to all patients on the COPD register (n=69) by post, excluding those already diagnosed with depression (n=3). We sent appointments to all responders with moderate to severe depression and offered them treatment including antidepressants and pulmonary rehabilitation if the diagnosis was confirmed. RESULTS: Of the 66 patients to whom we sent questionnaires, 43 were returned completed and 13 of these had significant depression (30%). 10 of these patients were contactable and attended for review. The diagnosis of depression was confirmed in all 10 cases. Treatment options were discussed; five chose antidepressant medication, three chose pulmonary rehabilitation and two declined treatment. CONCLUSION: We identified and treated a significant number of depressed COPD patients in a general practice setting using this screening method. This method could have wider applications for screening, although further trials are needed. 相似文献
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Kamran Sardari Ehsan Galedar Kakhki Mehrdad Mohri 《Comparative clinical pathology》2007,16(3):197-200
Ten bulls (age 7 months, weight 302 ± 15 kg) were used in this study. After sterile preparation of skin, a full thickness
wound (20 × 20 mm) was created in each bull. The bulls were randomly assigned into two groups: group 1 received 6 ml Theranekron
subcutaneously and group 2 penicillin banzatine 10,000 IU/kg IM. These doses were repeated 6 days after initial wounding.
At days 0, 3, 6, 10 and 14, digital photographs were taken from the wounds to calculate wound contraction and epithelialization
using geometry. Chi-square test was performed for statistical analysis using SPSS 9 for Windows. There was no significant
differences in wound contraction between trial groups (P > 0.05) but a statistical difference was seen in epithelialization between groups (P < 0.05). Epithelialization is one of the most important factors in wound healing. According to the results of the present
study, Theranekron can significantly stimulate epithelialization in full thickness wounds in cows during the first 14 days
of healing. 相似文献
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