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Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib:Multicenter French clinical experience in real-life after matching

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1510-1527页

作者： Xavier Adhoute Marie De Matharel Laurent Mineur Guillaume Pénaranda Dann Ouizeman Clemence Toullec Albert Tran paul castellani Armelle Rollet Valérie Oules HervéPerrier Si Nafa Si Ahmed Marc Bourliere Rodolphe Anty Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseille 13000France Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNice 06000France Department of Oncology Institut Sainte-CatherineAvignon 84000France Department of Biostatistics AlphaBio LaboratoryMarseille 13000France

BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common *** only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG)and cabozantinib(CBZ),but no comparative real-life studies are *** To evaluate the progression-free survival(PFS)of patients treated with REG or CBZ,we investigated the disease control rate(DCR),overall survival(OS),and safety of both *** identify the variables associated with disease progression over *** A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers(Avignon,Marseille,and Nice)between January 2017 and March 2021 using propensity score *** and OS were assessed using the Kaplan-Meier *** analysis(MA)of progression risk factors over time was performed in matched-pair *** Fifty-eight patients 68(62-74)years old with HCC,Barcelona clinic liver cancer(BCLC)B/C(86%),Child-Pugh(CP)-A/B(24%)received REG for 3.4(1.4-10.5)mo as second-line *** patients 68(60-73)years,BCLC B/C(75%),CP-A/B(25%)received CBZ for 3.7(1.8-4.9)mo after first-line treatment with sorafenib[3(2-4)(CBZ)vs 4(2.9-11.8)mo(REG),P=0.0226].Twenty percent of patients received third-line *** matching,PFS and DCR were not significantly different after a median follow-up of 6.2(2.7-11.7)mo(REG)vs 5.2(4-7.2)mo(CBZ),P=*** was no difference in grade 3/4 toxicities,dose reductions,or *** OS of CP-A patients was 8.3(5.2-24.8)vs 4.9(1.6-11.7)mo(CP-B),P=*** MA of risk factors for progression over time identified C-reactive protein(CRP)>10 mg/L,neutrophil-to-lymphocyte ratio(NLR)>3,and aspartate aminotransferase(AST)>45 IU as predictive *** This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced *** levels of inflam

关键词： Hepatocellular carcinoma Regorafenib Cabozantinib C-reactive protein Neutrophillymphocyte ratio

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Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma:Real-life Data on Liver Disease,Treatment and Prognosis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1106-1117页

作者： Xavier Adhoute Olivia Pietri Guillaume Pénaranda Thomas Wolf Patrick Beaurain Olivier Monnet Arthur Laquière Justine Bonomini Frédéric Neumann Olivier Levrel Jean-Pascal Buono Xavier Hanna paul castellani HervéPerrier Marc Bourliere Rodolphe Anty Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseilleFrance Department of Biostatistics AlphaBio-Biogroup LaboratoryMarseilleFrance Department of Radiology Hôpital Saint-JosephMarseilleFrance Department of Clinical Research Hôpital Saint-JosephMarseilleFrance Medipath EguillesFrance Department of Hepatobiliary Surgery Hôpital Saint-JosephMarseilleFrance Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNiceFrance

Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and *** real-life study investigated their characteristics,treatment modalities,and ***:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December *** survival(OS)was estimated by the Kaplan-Meier *** of iCCAs after histological and radiological review,and molecular profiling was ***:HCCs patients were more likely to have early-stage disease than iCCA *** patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was *** of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)*** of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)*** patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor *** significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA ***:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic *** entities had a dismal prognosis at advanced ***,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

关键词： Intrahepatic cholangiocarcinoma Hepatocellular carcinoma Cirrhosis NASH Oncogenic alterations

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Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

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Neural Regeneration Research 2024年第12期19卷 2581-2582页

作者： Shuyu Zhang paul Lingor Department of Neurology School of MedicineUniversity Hospital rechts der IsarTechnical University of MunichMunichGermany Department of Neurology University Medical Center GöttingenGöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center GöttingenGöttingenGermany

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) *** a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble *** forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

关键词： atrophy endogenous atypical

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Expected outcomes and patients’selection before chemoembolization—“Six-and-Twelve or Pre-TACE-Predict”scores may help clinicians:Real-life French cohorts results

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World Journal of Clinical Cases 2021年第18期9卷 4559-4572页

作者： Xavier Adhoute Edouard Larrey Rodolphe Anty Patrick Chevallier Guillaume Penaranda Albert Tran Jean-Pierre Bronowicki Jean-Luc Raoul paul castellani HervéPerrier Olivier Bayle Olivier Monnet Bernard Pol Marc Bourliere Department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseille 13008France Department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNice 06000France Department of Radiology Hôpital Universitaire de l’ArchetNice 06000France Statistics Department AlphaBio LaboratoryMarseille 13003France Department of Gastroenterology and Hepatology Centre Hospitalo-Universitaire de NancyVandoeuvre les Nancy 54511France Department of Medical Oncology Institut de Cancérologie de l’OuestSite de NantesNantes 44805France Department of Radiology Hôpital Saint-JosephMarseille 13008France Department of Hepatobiliary Surgery Hôpital Saint-JosephMarseille 13008France

BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in *** propose two new models to better stratify patients and maximize clinical benefit:“6 and 12”and“pre/post-TACE-predict”(TACE,transarterial chemoembolization).METHODS We evaluated and compared their performance in predicting overall survival with other systems{Barcelona Clinic Liver Cancer(BCLC),Albumin-Bilirubin(ALBI)and NIACE[Number of tumor(s),Infiltrative HCC,alpha-fetoprotein,Child-Pugh(CP),and performance status]}in two HCC French cohorts of different stages enrolled between 2010 and *** The cohorts included 324 patients classified as BCLC stages A/B(cohort 1)and 137 patients classified as BCLC stages B/C(cohort 2).The majority of the patients had cirrhosis with preserved liver function.“Pre-TACE-predict”and“6 and 12”models identified three distinct categories of patients exhibiting different prognosis in cohort ***,their prognostic value was no better than the BCLC system or NIACE *** function based on CP and ALBI grades significantly impacted patient ***,the“post-TACE-predict”model had a higher predictive value than other *** stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient(cohort 2).CONCLUSION The newly proposed“Pre-TACE-predict”and“6 and 12”models offer an interesting stratification into three categories in a recommended TACE population,as they identify poor candidates,those with partial control and durable *** models'contribution was reduced in a population with advanced stage HCCs.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Pre-TACEpredict Six-and-twelve Barcelona Clinic Liver Cancer Prognosis

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Tensor perturbations from bounce inflation scenario in f(Q)gravity

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Science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 78-92页

作者： Kun Hu Tanmoy paul Taotao Qiu Institute of Astrophysics Central China Normal UniversityWuhan 430079China School of Physics Huazhong University of Science and TechnologyWuhan 430074China National Institute of Technology Jamshedpur Department of PhysicsJamshedpur 831014India

In this paper,we construct a bounce inflation cosmological scenario in the framework of the modified symmetric teleparallel gravity,namely f(Q)theory,and investigate the tensor perturbations *** is well-known,the tensor perturbations generated in the very early Universe(inflation and pre-inflation regions)can account for the primordial gravitational waves(PGWs)that are to be detected by the next generation of GW *** discuss the stability condition of the tensor perturbations in the bounce inflation process and investigate in detail the evolution of the perturbation *** general form of the tensor power spectrum is obtained both for large as well as small scale *** a result,we show both kinds of modes(short or long wavelength modes),and the tensor spectrum may get a positive tilt in the parametric range where the tensor perturbation proves to be stable—this interestingly hints an enhancement of gravitational waves’amplitude in the background of the f(Q)bounce-inflation ***,we study the LQC-like scenario as a specific case of our model,in which,the primordial tensor power spectrum turns out to be nearly scale-invariant on both small and large scales.

关键词： bounce cosmology modified gravity cosmological perturbations

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