AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and a...AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver展开更多
Background: Confronted to the increasing suicide rate in children, clinicians have to better understand and predict suicide-related behaviours (SRBs) in children with and without depressive symptoms. Aims: To investig...Background: Confronted to the increasing suicide rate in children, clinicians have to better understand and predict suicide-related behaviours (SRBs) in children with and without depressive symptoms. Aims: To investigate associations among suicidal tendencies (thoughts and/or attempts), depression and children’s perceptions of subjective quality of life. Methods: This was a cross-sectional study of 157 children of 6 - 13-year-old. Results: Children who attempted or thought of suicide reported goodless subjective quality of life than nonsuicidal children did, and children who thought of or attempted suicide reported higher levels of depressive symptoms than nonsuicidal children. Limitations: A more rigorous approach to investigating suicidal ideation and depressive symptomatology as a diagnostic interview based on the DSM-IV-TR will be valuable to future progress in understanding children’s suicidality. Conclusions: Results may reflect the confirmation of depressive symptoms as risk factors for suicidality and underline the high importance of social and emotional life context among suicidal children. For this reason, more effective recognition and comprehension of the underlying affective and social conditions of children with suicidality have special importance to prevent future suicidal behaviour during adolescence.展开更多
Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retr...Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retrieved during the endovascular thrombectomy procedure.Despite ongoing developments and progress in AIS imaging techniques,it is not yet possible to conclude definitively regarding thrombus characteristics that could advise on the probable efficacy of thrombolysis or thrombectomy in advance of treatment.Intraprocedural devices with dignostic capabilities or new clinical imaging approaches are needed for better treatment of AIS patients.In this review,what is known about the composition of the thrombi that cause strokes and the evidence that thrombus composition has an impact on success of acute stroke treatment has been examined.This review also discusses the evidence that AIS thrombus composition varies with aetiology,questioning if suspected aetiology could be a useful indicator to stroke physicians to help decide the best acute course of treatment.Furthermore,this review discusses the evidence that current widely used radiological imaging tools can predict thrombus composition.Further use of new emerging technologies based on bioimpedance,as imaging modalities for diagnosing AIS and new medical device tools for detecting thrombus composition in situ has been introduced.Whether bioimpedance would be beneficial for gaining new insights into in situ thrombus composition that could guide choice of optimum treatment approach is also reviewed.展开更多
During their life,T cells are constantly circulating throughout the body.Sphingosine-1-phosphate(S1P),a sphingolipid metabolite,triggers T cell egress from the thymus and secondary lymphoid organs(SLO)into the lymph a...During their life,T cells are constantly circulating throughout the body.Sphingosine-1-phosphate(S1P),a sphingolipid metabolite,triggers T cell egress from the thymus and secondary lymphoid organs(SLO)into the lymph and the blood.This phenomenon is dependent on the S1P gradient between lymphoid organs(including thymus and SLO)and the lymphatic and blood vessels,which exhibit low,intermediate and high S1P levels,respectively.T cells follow the S1P gradient via the engagement of the G-protein-coupled receptor S1P receptor 1(S1P1)expressed on T cells.1 S1P production is regulated by various sphingolipid-metabolizing enzymes.The sphingosine kinases 1 and 2(SKs),encoded by Sphk1 and Sphk2,phosphorylate the sphingosine(Sph)into S1P.Conversely,S1P can be dephosphorylated to Sph by S1P phosphatases 1 and 2,encoded by Sgpp1 and Sgpp2.Alternatively,S1P can be irreversibly degraded by the S1P Lyase(SPL),encoded by Sgpl1,into phosphoethanolamine and hexadecenal.展开更多
文摘AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver
文摘Background: Confronted to the increasing suicide rate in children, clinicians have to better understand and predict suicide-related behaviours (SRBs) in children with and without depressive symptoms. Aims: To investigate associations among suicidal tendencies (thoughts and/or attempts), depression and children’s perceptions of subjective quality of life. Methods: This was a cross-sectional study of 157 children of 6 - 13-year-old. Results: Children who attempted or thought of suicide reported goodless subjective quality of life than nonsuicidal children did, and children who thought of or attempted suicide reported higher levels of depressive symptoms than nonsuicidal children. Limitations: A more rigorous approach to investigating suicidal ideation and depressive symptomatology as a diagnostic interview based on the DSM-IV-TR will be valuable to future progress in understanding children’s suicidality. Conclusions: Results may reflect the confirmation of depressive symptoms as risk factors for suicidality and underline the high importance of social and emotional life context among suicidal children. For this reason, more effective recognition and comprehension of the underlying affective and social conditions of children with suicidality have special importance to prevent future suicidal behaviour during adolescence.
基金funded by European Regional Development Fund(13/RC/2073_2)Sensome(No grant number),Science Foundation Ireland(13/RC/2073_2).
文摘Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retrieved during the endovascular thrombectomy procedure.Despite ongoing developments and progress in AIS imaging techniques,it is not yet possible to conclude definitively regarding thrombus characteristics that could advise on the probable efficacy of thrombolysis or thrombectomy in advance of treatment.Intraprocedural devices with dignostic capabilities or new clinical imaging approaches are needed for better treatment of AIS patients.In this review,what is known about the composition of the thrombi that cause strokes and the evidence that thrombus composition has an impact on success of acute stroke treatment has been examined.This review also discusses the evidence that AIS thrombus composition varies with aetiology,questioning if suspected aetiology could be a useful indicator to stroke physicians to help decide the best acute course of treatment.Furthermore,this review discusses the evidence that current widely used radiological imaging tools can predict thrombus composition.Further use of new emerging technologies based on bioimpedance,as imaging modalities for diagnosing AIS and new medical device tools for detecting thrombus composition in situ has been introduced.Whether bioimpedance would be beneficial for gaining new insights into in situ thrombus composition that could guide choice of optimum treatment approach is also reviewed.
文摘During their life,T cells are constantly circulating throughout the body.Sphingosine-1-phosphate(S1P),a sphingolipid metabolite,triggers T cell egress from the thymus and secondary lymphoid organs(SLO)into the lymph and the blood.This phenomenon is dependent on the S1P gradient between lymphoid organs(including thymus and SLO)and the lymphatic and blood vessels,which exhibit low,intermediate and high S1P levels,respectively.T cells follow the S1P gradient via the engagement of the G-protein-coupled receptor S1P receptor 1(S1P1)expressed on T cells.1 S1P production is regulated by various sphingolipid-metabolizing enzymes.The sphingosine kinases 1 and 2(SKs),encoded by Sphk1 and Sphk2,phosphorylate the sphingosine(Sph)into S1P.Conversely,S1P can be dephosphorylated to Sph by S1P phosphatases 1 and 2,encoded by Sgpp1 and Sgpp2.Alternatively,S1P can be irreversibly degraded by the S1P Lyase(SPL),encoded by Sgpl1,into phosphoethanolamine and hexadecenal.
