Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athlete...Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.展开更多
Background:While preliminary reports on resection following downstaging using transarterial radioembolization(TARE)for intermediate or advanced hepatocellular carcinomas(HCCs)reported promising oncological outcomes,th...Background:While preliminary reports on resection following downstaging using transarterial radioembolization(TARE)for intermediate or advanced hepatocellular carcinomas(HCCs)reported promising oncological outcomes,there’s a notable gap in the literature concerning post operative morbidity.Contrary to post hepatectomy liver failure(PHLF),damages to the bile ducts and their potential consequences have been poorly evaluated.Thus,our aim was to explore postoperative complications in HCC patients undergoing liver resection after Y90 TARE,focusing particularly on biliary complications.Methods:Conducted from June 2015 to December 2022,this retrospective study involved 30 HCC patients undergoing liver resection post-TARE.Comprehensive data on surgical procedures,complications,and follow-up were collected.Logistic regression analyses were conducted,starting with univariate analysis followed by multivariate analysis,focusing on variables with a significance level below P<0.2.Results:The objective response rate(ORR)in the TARE-treated area was 97%at 3 months.Survival outcomes showed a median overall survival(OS)of 5.1 years and progression-free survival(PFS)of 3.5 years post-liver resection.The study found a 40%(12 out of 30 patients)rate of severe postoperative complications and a 7%(2 out of 30 patients)90-day mortality rate.After liver resection,grade B bile leaks occurred in 20%(6 out of 30)of patients,with a third experiencing recurrence.Biliary-specific mortality was 9%.After multivariate analysis,only the interval between TARE and surgery emerged a significant risk factor for biliary complications,showing increased odds of bile leaks if surgery occurred 3-6 months post-TARE compared to after 6 months.Conclusions:This study highlights the importance of timing between TARE and surgery,suggesting a waiting period of at least 6 months.Such timing not only enhances the radiation effects of TARE but also optimizes both future liver remnant growth and patient selection.展开更多
Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)...Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)on liver explants.In patients with portal vein tumoral thrombus(PVTT),multifocal or large tumors,TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population.Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods:In this retrospective study,we evaluated safety,radiological and pathological response and outcomes in HCC patients with PVTT,multifocal or large tumors,who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results:Between December 2015 and October 2021,18 unresectable patients(14/18 with PVTT)had surgery(16 resections,2 liver transplantations)6.2 months(range,2-14.6 months)after a single Y90 treatment.No 90-day mortality was reported.Objective modified response criteria in solid tumors(mRECIST)response were noted in all but one patient.Complete and extensive(50-99%)necrosis was observed in 36%and 45%of tumors,respectively.The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis(P=0.045).Median overall survival and progression-free survival(PFS)were respectively of 61.8 months[95%CI:31.4 months-not reached(NR)]and 49.3 months(95%CI:14 months-NR).PFS was longer in patients with complete imaging response[median NR(none recurred or died)vs.21.5 months(95%CI:10.1 months-NR),P<0.001]and in those with complete pathological response[median NR vs.22.5 months(95%CI:10.1 months-NR),P<0.001].Conclusions:Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT,large or multifocal HCC.Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.展开更多
Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is kn...Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.展开更多
基金supported by YAKHA Sport,Franceby the Platform 3A,funded by the European Regional Development Fund+3 种基金the French Ministry of Research,Higher Education and Innovationthe Provence-Alpes-Côte-d'Azur regionthe Departmental Council of Vauclusethe Urban Community of Avignon。
文摘Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.
文摘Background:While preliminary reports on resection following downstaging using transarterial radioembolization(TARE)for intermediate or advanced hepatocellular carcinomas(HCCs)reported promising oncological outcomes,there’s a notable gap in the literature concerning post operative morbidity.Contrary to post hepatectomy liver failure(PHLF),damages to the bile ducts and their potential consequences have been poorly evaluated.Thus,our aim was to explore postoperative complications in HCC patients undergoing liver resection after Y90 TARE,focusing particularly on biliary complications.Methods:Conducted from June 2015 to December 2022,this retrospective study involved 30 HCC patients undergoing liver resection post-TARE.Comprehensive data on surgical procedures,complications,and follow-up were collected.Logistic regression analyses were conducted,starting with univariate analysis followed by multivariate analysis,focusing on variables with a significance level below P<0.2.Results:The objective response rate(ORR)in the TARE-treated area was 97%at 3 months.Survival outcomes showed a median overall survival(OS)of 5.1 years and progression-free survival(PFS)of 3.5 years post-liver resection.The study found a 40%(12 out of 30 patients)rate of severe postoperative complications and a 7%(2 out of 30 patients)90-day mortality rate.After liver resection,grade B bile leaks occurred in 20%(6 out of 30)of patients,with a third experiencing recurrence.Biliary-specific mortality was 9%.After multivariate analysis,only the interval between TARE and surgery emerged a significant risk factor for biliary complications,showing increased odds of bile leaks if surgery occurred 3-6 months post-TARE compared to after 6 months.Conclusions:This study highlights the importance of timing between TARE and surgery,suggesting a waiting period of at least 6 months.Such timing not only enhances the radiation effects of TARE but also optimizes both future liver remnant growth and patient selection.
文摘Background:Transarterial radioembolization(TARE)has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas(HCCs)with high rates of complete pathological necrosis(CPN)on liver explants.In patients with portal vein tumoral thrombus(PVTT),multifocal or large tumors,TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population.Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods:In this retrospective study,we evaluated safety,radiological and pathological response and outcomes in HCC patients with PVTT,multifocal or large tumors,who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results:Between December 2015 and October 2021,18 unresectable patients(14/18 with PVTT)had surgery(16 resections,2 liver transplantations)6.2 months(range,2-14.6 months)after a single Y90 treatment.No 90-day mortality was reported.Objective modified response criteria in solid tumors(mRECIST)response were noted in all but one patient.Complete and extensive(50-99%)necrosis was observed in 36%and 45%of tumors,respectively.The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis(P=0.045).Median overall survival and progression-free survival(PFS)were respectively of 61.8 months[95%CI:31.4 months-not reached(NR)]and 49.3 months(95%CI:14 months-NR).PFS was longer in patients with complete imaging response[median NR(none recurred or died)vs.21.5 months(95%CI:10.1 months-NR),P<0.001]and in those with complete pathological response[median NR vs.22.5 months(95%CI:10.1 months-NR),P<0.001].Conclusions:Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT,large or multifocal HCC.Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.
文摘Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.
