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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss christine Heuer Marina Herwerth Institute of pharmacology and Toxicology University of Zurich Neuroscience Center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(p1 and p2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by p2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with p2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of p2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of p2 receptors with several disorders from this field, the use of p2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system p2 receptor inhibitors suramin

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promoting Older Adults' Engagement in Disaster Settings: An Introduction to the Special Issue

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International Journal of Disaster Risk Science 2024年第2期15卷 181-185页

作者： Haorui Wu christine AWalsh Julie LDrolet Kyle Breen Faculty of Health School of Social WorkDalhousie UniversityHalifaxNS B3H 4R2Canada Faculty of Social Work University of CalgaryCalgaryAB T2N 1N4Canada Faculty of Social Work Central&Northern Alberta RegionUniversity of CalgaryEdmontonAB T5J 4P6Canada

1 Introduction Globally, surging extreme events and the escalating aging population present ongoing and severe challenges to the full spectrum of international community development(for example, social, health, and ec... 详细信息

关键词： extreme challenges economic

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白介素-33至白介素-13信号级联调节小鼠胃组织上皮化生

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英国医学杂志中文版 2018年第7期21卷 418-418页

作者： christine p petersen Anne R Meyer Carlo De Salvo Eunyoung Choi Cameron Schlegel Alec petersen Amy C Engevik Nripesh prasad Shawn E Levy R Stokes peebles Theresa T pizarro James R Goldenring 李佳宁(译) 吴东(校) 不详北京协和医院消化科

目的选择性活化巨噬细胞（Alternativelyactivated macrophages, M2）与胃部解痉多肽表达性化生（spasmolytic polypeptide-expressingmetaplasia, SpEM）过程相关。然而，诱导SpEM的确切机制及关键介质尚不明确。研究设计为确定这一... 详细信息

目的选择性活化巨噬细胞（Alternativelyactivated macrophages, M2）与胃部解痉多肽表达性化生（spasmolytic polypeptide-expressingmetaplasia, SpEM）过程相关。然而，诱导SpEM的确切机制及关键介质尚不明确。研究设计为确定这一过程中的关键基因，分离胃部SpEM小鼠（DMp-777处理）及高级胃部SpEM小鼠（L635处理）胃体的巨噬细胞进行RNA测序。评估白介素．33、白介素-33受体（ST2）及白介素-13基因敲除小鼠，经L635处理急性壁细胞缺失后对上皮细胞化生过程的影响。结果胃部上皮化生相关性巨噬细胞中可鉴定出M2极化亚群。高级胃部SpEM小鼠巨噬细胞中自介素-33的表达显著上调。L635可在野生型小鼠胃组织中诱导上皮化生，但在白介素-33及白介素．33受体敲除鼠中未观察到这一现象。尽管在诱导上皮化生过程中不需白介素．5及白介素-9，白介素-13基因敲除小鼠无法在L635诱导下发生上皮化生。对白介素-33受体基因敲除小鼠应用白介素-13，可重新诱导急性壁细胞缺失后的上皮化生。结论壁细胞缺失后上皮化生及巨噬细胞极化过程通过白介素．33及白介素-13的细胞信号网络协调进行，将损伤应答过程中固有黏膜机制及M2浸润联系起来。

关键词： IL-13 组织变形调整老鼠串联信号胃

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Subsequent total joint arthroplasty: Are we learning from the first stage?

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World Journal of Orthopedics 2024年第3期15卷 230-237页

作者： christine Jiang Wu Colin penrose Sean patrick Ryan Michael paul Bolognesi Thorsten Markus Seyler Samuel Secord Wellman Department of Orthopaedic Surgery Duke University HospitalDurhamNC 27710United States Department of Orthopaedic Surgery Midwest Center for Joint ReplacementIndianapolisIN 46241United States

BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource *** degenerative conditions progress in multiple joints,many patients undergo multiple *** To determine if both physicians and patients learn from the patient’s initial arth-roplasty,resulting in improved outcomes following the second *** The institutional database was retrospectively queried for primary total hip arth-roplasty(THA)and total knee arthroplasty(TKA).patients with only unilateral THA or TKA,and patients undergoing same-day bilateral TJA,were *** demographics,comorbidities,and implant sizes were collected at the time of each procedure and patients were stratified by first vs second *** metrics evaluated included operative time,length of stay(LOS),disposition,90-d readmissions and emergency department(ED)*** A total of 642 patients,including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA,were *** was no significant difference in demographics or comorbidities between the first and second procedure,which were separated by a mean of 285 *** THA and TKA,LOS was significantly less for the second surgery,with 66%of patients having a shorter hospitalization(ppatients had significantly decreased operative time only when the same sized implant was utilized(p=0.025).The vast majority(93.3%)of patients were discharged to the same type of location following their second ***,when a change in disposition was present from the first surgery,patients were significantly more likely to be discharged to home after the second procedure(p=0.033).There was no difference between procedures for post-operative readmissions(p=0.438)or ED visits(p=0.915).CONCLUSION After gaining valuable experience recovering from the initial surgery,a patient’s perioperative outcomes are improved for their second *** may

关键词： Staged total joint arthroplasty Asynchronous total joint arthroplasty Subsequent total joint arthroplasty Contralateral total joint arthroplasty perioperative outcomes

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Comparison of fungal vs bacterial infections in the medical intensive liver unit:Cause or corollary for high mortality?

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World Journal of Hepatology 2024年第3期16卷 379-392页

作者： Sarah Khan Hanna Hong Stephanie Bass Yifan Wang Xiao-Feng Wang Omar T Sims christine E Koval Aanchal Kapoor Christina C Lindenmeyer Department of Internal Medicine Cleveland ClinicClevelandOH 44195United States Cleveland Clinic Lerner College of Medicine Cleveland ClinicClevelandOH 44195United States Department of pharmacy Cleveland ClinicClevelandOH 44195United States Department of Quantitative Health Sciences/Biostatistics Section Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Hepatology and NutritionCleveland ClinicClevelandOH 44195United States Department of Infectious Disease Cleveland ClinicClevelandOH 44195United States Department of Critical Care Medicine Cleveland ClinicClevelandOH 44195United States

BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as *** data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver *** To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial *** From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial *** compared outcomes between patients admitted to the MILU with fungal infections to bacterial *** was extracted through chart *** All fungal infections were due to Candida species,and were most frequently blood *** among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,pped grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,p=0.02).patients in the fungal cohort had increased use of vasopressors(96%vs 70%,p=0.04),mechanical ventilation(96%vs 65%,pp=0.014).On MILU admission,the fungal cohort had significantly higher Acute physiology and Chronic Health Evaluation(108 vs 91,p=0.003),Acute physiology Score(86 vs 65,p=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,p=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,p=0.2).patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical *** Mortality was worse among patients with fungal infections,likely attributable to severe ACLF *** studies examinin

关键词： Fungal Infection Sepsis Acute on chronic liver failure Intensive care

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Evaluating pediatric ureteropelvic junction obstruction:Dynamic magnetic resonance urography vs renal scintigraphy 99mtechnetium mercaptoacetyltriglycine

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World Journal of Radiology 2024年第3期16卷 49-57页

作者： Yousuf Al-Shaqsi Matthieu peycelon Annabel paye-Jaouen Elisabeth Carricaburu Anca Tanase christine Grapin-Dagorno Alaa El-Ghoneimi Department of pediatric Surgery Sultan Qaboos University HospitalMuscat 123Oman Service de Chirurgie Viscérale et Urologie pédiatrique Hôpital Universitaire Robert-DebréAssistance-Publique Hôpitaux de ParisParis 75019France Centre de Références Maladies Rares Malformations Rares des Voies Urinaires(MARVU)Paris 97019France Facultéde Médecine Universitéde ParisParis 75006France Service d’Imagerie pédiatrique Hôpital Universitaire Robert-DebréAssistance-Publique Hôpitaux de ParisParis 75019France Universitéparis 13 Sorbonne Paris CitéParis 75013France

BACKGROUND Ureteropelvic junction obstruction(UpJO)is a common congenital urinary tract disorder in *** can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic *** To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography(dMRU)and scintigraphy 99m-technetium mercaptoacetyltriglycine(MAG-3)for the functional evaluation of *** Between 2016 and 2020,126 patients with UpJO underwent surgery at Robert Debré*** these,83 received a prenatal diagnosis,and 43 were diagnosed during *** of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging *** renal function was evaluated preoperatively using scintigraphy MAG-3(n=28),dMRU(n=53),or both(n=40).In this study,we included patients who underwent surgery for UpJO and scintigraphy MAG-3+dMRU but excluded those who underwent only scintigraphy MAG-3 or *** patients were divided into groups A(pancy)and B(>10%discrepancy).We examined the discrepancy in split renal function between the two modalities and investigated the possible risk *** The split renal function between the two kidneys was compared in 40 patients(28 boys and 12 girls)using scintigraphy MAG-3 and *** renal function,as determined using both modalities,showed a difference of10%in 9 *** of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both *** Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UpJO.

关键词： Uteropelvic junction obstruction Scintigraphy 99m-technetium mercaptoacetyltriglycine Magnetic resonance imaging Dynamic contrast-enhanced magnetic resonance urography

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Is convenience really king? Comparative evaluation of catastrophic costs due to tuberculosis in the public and private healthcare sectors of Viet Nam: a longitudinal patient cost study

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贫困所致传染病(英文) 2024年第2期13卷 17-28页

作者： Nguyen Hoa Binh Quang Vo Luan Nguyen Forse Rachel Jeanette Wiemers Anja Maria christine Huynh Huy Ba Dong Thuy Thi Thu phan Yen Thi Hoang Creswell Jacob Dang Thi Minh Ha Nguyen Lan Huu Shedrawy Jad L?nnroth Knut Nguyen Tuan Dinh Van Dinh Luong Annerstedt Kristi Sidney Codlin Andrew James National Lung Hospital Ha Noi Viet Nam Friends for International TB Relief Ha Noi Viet Nam Department of Global public Health WHO Collaboration Centre On Tuberculosis and Social Medicine Karolinska Institute Stockholm Sweden Stop TB partnership Geneva Switzerland pham Ngoc Thach Hospital Ho Chi Minh City Viet Nam

Background In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private *** Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB program (NTp) in Ha Noi, Hai phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate *** The pre-treatment median monthly household income was significantly higher in the private sector versus NTp cohort (USD 868 vs USD 578;p=0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313;p=0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTp participants (USD 754 vs USD 164;pphic costs between the two cohorts (private: 55% vs NTp: 52%;p=0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio [(aOR=13.71; 95% confidence interval (CI): 1.36–138.14;p=0.026], unemployment during treatment (aOR=10.86; 95%CI: 2.64–44.60;pperiencing TB-related stigma (aOR=37.90; 95%CI: 1.72–831.73;p=0.021).Conclusions persons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the

关键词： Tuberculosis patient cost Catastrophic cost private sector Comparative analysis Viet Nam

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Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

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Journal of Sport and Health Science 2024年第6期13卷 851-862页

作者： Ki-Yong An Fernanda Z.Arthuso Myriam Filion Spencer J.Allen Stephanie M.Ntoukas Gordon J.Bell Jessica McNeil Qinggang Wang Margaret L.McNeely Jeff K.Vallance Lin Yang S.Nicole Culos-Reed Leanne Dickau John R.Mackey christine M.Friedenreich Kerry S.Courneya Faculty of Kinesiology Sportand RecreationCollege of Health SciencesUniversity of AlbertaEdmonton T6G 2H9Canada Department of Kinesiology School of Health and Human SciencesUniversity of North Carolina at GreensboroGreensboroNC 27412USA Department of Cancer Epidemiology and prevention Research Cancer Care AlbertaAlberta Health ServicesCalgary T2S 3C3Canada Faculty of Rehabilitation Medicine University of AlbertaEdmonton T6G 2H9Canada Faculty of Health Disciplines Athabasca UniversityAthabasca T9S 3A3Canada Department of Oncology Cumming School of MedicineUniversity of CalgaryCalgary T2N 4N1Canada Faculty of Kinesiology University of CalgaryCalgary T2N 1N4Canada Faculty of Medicine and Dentistry University of AlbertaEdmonton T6G 2H9Canada

Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and *** and managing breast cancer-related symptoms soon after diagnosis is *** purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer ***:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of *** measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body *** measures included depression,sleep quality,and *** multivariable logistic regression was performed for ***:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate *** multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(ppoor sleep quality(p=0.009),significant fatigue(p=0.008),any symptom(pple symptoms(ppeak)demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest *** strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple ***,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diag

关键词： Breast cancer Fatigue Depression Sleep quality Cardiorespiratory fitness

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On Northern Hemisphere Wave patterns Associated with Winter Rainfall Events in China

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Advances in Atmospheric Sciences 2018年第8期35卷 125-138页

作者： Claudia christine STEpHAN Yan Ho NG Nicholas p. KLINGAMAN National Centre for Atmospheric Science - Climate Department of Meteorology University of Reading Reading RG6 6BB United Kingdom Department of Meteorology University of Reading Reading RG6 6BB United Kingdom

During extended winter （November-April）, 43% of the intraseasonal rainfall variability in China is explained by three spatial patterns of temporally coherent rainfall, These patterns were identified with empirical orthogonal teleconnection （EOT） analysis of observed 1982-2007 pentad rainfall anomalies and connected to midlatitude disturbances. However, ex- amination of individual strong EOT events shows that there is substantial inter-event variability in their dynamical evolution, which implies that precursor patterns found in regressions cannot serve as useful predictors. To understand the physical nature and origins of the extratropical precursors, the EOT technique is applied to six simulations of the Met Office Unified Model at horizontal resolutions of 200-40 km, with and without air-sea coupling. All simulations reproduce the observed precursor patterns in regressions, indicating robust underlying dynamical processes. Further investigation into the dynamics associated with observed patterns shows that Rossby wave dynamics can explain the large inter-event variability. The results suggest that the appaxently slowly evolving or quasi-stationaxy waves in regression analysis are a statistical amalgamation of more rapidly propagating waves with a variety of origins and properties.

关键词： rainfall in China spring flooding Rossby wave dynamics EOT analysis predictability teleconnections

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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre patrick Villarese Vahid Asnafi christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud paul Isenring Guillaume Canaud Universitéparis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of pIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of pIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a pI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying pIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of pIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports pI3Kαinhibition as a promising therapeutic strategy in patients with pIK3CA or TEK-related capillary venous malformations.

关键词： pIK3CA malformations venous

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