Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption,increases bone mass,and reduces fracture risk.Denosumab discontinuation causes an extensive wave of rebound resorption,but the cellular mecha...Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption,increases bone mass,and reduces fracture risk.Denosumab discontinuation causes an extensive wave of rebound resorption,but the cellular mechanisms remain poorly characterized.We utilized in situ hybridization(ISH)as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway.ISH was performed across species,skeletal sites,and following recombinant OPG(OPG:Fc)and parathyroid hormone 1–34(PTH)treatment of mice.展开更多
In a recent study published in Cell,Xu et al.have uncovered a critical role for the endoplasmic reticulum(ER)stress sensor inositol-requiring enzyme 1 alpha(IRE1α)in modulating the immunogenic effects of taxane chemo...In a recent study published in Cell,Xu et al.have uncovered a critical role for the endoplasmic reticulum(ER)stress sensor inositol-requiring enzyme 1 alpha(IRE1α)in modulating the immunogenic effects of taxane chemotherapy in triple-negative breast cancer(TNBC).They reveal how IRE1αacts as a defense mechanism in cancer cells,preventing the accumulation of danger signals and subsequent immunogenic cell death(ICD).展开更多
BACKGROUND There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD)events.AIM To determine if there is an ...BACKGROUND There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD)events.AIM To determine if there is an independent association between NAFLD and CVD events.METHODS In the present study,valid outcome data of 4808 subjects were available for phase 2 of our cohort study.These subjects had been followed up for seven years from phase 1,beginning in 2009-2010 to phase 2 during 2016-2017.Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up.RESULTS The incidence of non-fatal CVD events in males with NAFLD was significantly higher(P=0.004)than in males without NAFLD.A positive association was demonstrated between NAFLD and non-fatal CVD events in males(Hazard ratio=1.606;95%CI:1.166-2.212;P=0.004)by the simple Cox proportional hazard model,but no independent association was detected between these in the multiple Cox models.CONCLUSION No independent association was detected between NAFLD and CVD.It is likely that diabetes mellitus and age may be the principle mediators in this regard.展开更多
Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive che...Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive chemoradiotherapy.Methods:Sixty consecutive women diagnosed with uterine cervical cancer FIGO 2009 stage IB1-IVA during 2011-2012 treated with definitive chemoradiotherapy/radiotherapy with curative intent at the Department of Gynaecological Oncology at Karolinska University Hospital were retrospectively included.A review of MRI reports and medical records with focus on follow-up interventions associated to imaging was performed.Results:On follow-up MRI three months post treatment,29/60 women had complete remission(mrCR),24/60 women had partial remission(mrPR)and 7/60 had progressive disease(mrPD).In patients with mrCR,no additional procedures were performed.The group with mrPR had 27 additional MRIs,3 PET/CT examinations and 9 biopsy procedures,none leading to diagnosis of residual tumour.Locoregional control rate was 96%after 6.5 months(median).No patient had cervical relapse only;2/53 had cervical relapse in combination with non-regional lymph nodes and distant relapse.There was no statistically significant difference in overall survival between patients with mrCR and mrPR(HR=2.2,P=0.21).Conclusion:Patients with residual changes on MRI at three months post treatment have a low risk for locoregional recurrence.If this is not recognised,follow-up MRI results in unnecessary additional procedures with low impact on treatment outcome.Further studies are needed regarding the most appropriate imaging modality and timing of post-treatment evaluation.展开更多
基金supported by Odense University Hospital’s Fund for Free Research (A5111)the Region of Southern Denmark’s Fund for Free Research (A955)+1 种基金the VELUX Foundations (VELUX25723)supported by the Novo Nordisk Foundation。
文摘Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption,increases bone mass,and reduces fracture risk.Denosumab discontinuation causes an extensive wave of rebound resorption,but the cellular mechanisms remain poorly characterized.We utilized in situ hybridization(ISH)as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway.ISH was performed across species,skeletal sites,and following recombinant OPG(OPG:Fc)and parathyroid hormone 1–34(PTH)treatment of mice.
基金supported by grants from the National Health and Medical Research Council of Australia(NHMRC2030541)+2 种基金funds from the Neurosurgical Research Foundation(NRF)supported by a Commonwealth Serum Laboratories Centenary Fellowship,Australian Medical Research Future Fund,National Health and Medical Research Council,Snowdome Foundation and the Leukemia Foundation grants 6619-21 and 6650-23The Leukemia&Lymphoma CMML Special Initiative Award.
文摘In a recent study published in Cell,Xu et al.have uncovered a critical role for the endoplasmic reticulum(ER)stress sensor inositol-requiring enzyme 1 alpha(IRE1α)in modulating the immunogenic effects of taxane chemotherapy in triple-negative breast cancer(TNBC).They reveal how IRE1αacts as a defense mechanism in cancer cells,preventing the accumulation of danger signals and subsequent immunogenic cell death(ICD).
文摘BACKGROUND There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease(NAFLD)and cardiovascular disease(CVD)events.AIM To determine if there is an independent association between NAFLD and CVD events.METHODS In the present study,valid outcome data of 4808 subjects were available for phase 2 of our cohort study.These subjects had been followed up for seven years from phase 1,beginning in 2009-2010 to phase 2 during 2016-2017.Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up.RESULTS The incidence of non-fatal CVD events in males with NAFLD was significantly higher(P=0.004)than in males without NAFLD.A positive association was demonstrated between NAFLD and non-fatal CVD events in males(Hazard ratio=1.606;95%CI:1.166-2.212;P=0.004)by the simple Cox proportional hazard model,but no independent association was detected between these in the multiple Cox models.CONCLUSION No independent association was detected between NAFLD and CVD.It is likely that diabetes mellitus and age may be the principle mediators in this regard.
文摘Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive chemoradiotherapy.Methods:Sixty consecutive women diagnosed with uterine cervical cancer FIGO 2009 stage IB1-IVA during 2011-2012 treated with definitive chemoradiotherapy/radiotherapy with curative intent at the Department of Gynaecological Oncology at Karolinska University Hospital were retrospectively included.A review of MRI reports and medical records with focus on follow-up interventions associated to imaging was performed.Results:On follow-up MRI three months post treatment,29/60 women had complete remission(mrCR),24/60 women had partial remission(mrPR)and 7/60 had progressive disease(mrPD).In patients with mrCR,no additional procedures were performed.The group with mrPR had 27 additional MRIs,3 PET/CT examinations and 9 biopsy procedures,none leading to diagnosis of residual tumour.Locoregional control rate was 96%after 6.5 months(median).No patient had cervical relapse only;2/53 had cervical relapse in combination with non-regional lymph nodes and distant relapse.There was no statistically significant difference in overall survival between patients with mrCR and mrPR(HR=2.2,P=0.21).Conclusion:Patients with residual changes on MRI at three months post treatment have a low risk for locoregional recurrence.If this is not recognised,follow-up MRI results in unnecessary additional procedures with low impact on treatment outcome.Further studies are needed regarding the most appropriate imaging modality and timing of post-treatment evaluation.
