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Targeted therapy for capillary-venous malformations

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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Modulation of the in vitro Oxidative Stress and Erythrocyte Cell Membrane Integrity Using Aqueous, Hydroethanolic and Ethanolic Stem-Barks Extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc

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Pharmacology & Pharmacy 2024年第3期15卷 39-61页

作者： patrick Hervé Diboue Betote Moustapha Gambo Abdoulaye Francis Ngolsou Esther Del Florence Ndedi Moni Adeline Sabine Fanta Yadang Fidel Castro Lah Weyepe Gabriel A. Agbor Nga Nnanga Maximilienne Ascension Nyegue Laboratory of Pharmacology and Drugs Discovery Centre for Research on Medicinal Plants and Traditional Medicine Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon Laboratory of Microbiology Department of Microbiology Faculty of Science University of Yaoundé I Yaoundé Cameroon Multidisciplinary Laboratory Department of Galenical Pharmacy and Pharmaceutical Law Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon Department of Physicochemical and Pharmaceutical Sciences Faculty of Health Sciences Abdou Moumouni University Niamey Niger Department of Pharmaceutical and Biological Sciences Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Laboratory of Pharmaceutical Technology Centre for Research on Medicinal Plants and Traditional Medicine Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon

Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH•, ABTS+•, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH• and ABTS+• scavenging activities (SC50) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with i

关键词： Greenwayodendron suaveolens Secondary Metabolites Oxidative Stress Antioxidant Activity Anti-Inflammatory Properties and Oral Acute Toxicity

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Urethroplasty among Elderly Men, Surgical Techniques and Outcomes

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Open Journal of Urology 2024年第3期14卷 179-187页

作者： Kwaku Addai Arhin Appiah George Amoah patrick Opoku Manu Maison Roland Azorliade Kwaku Otu-Boateng Douglas Arthur Dominic Annor Mintah Joseph Yorke George Asafu Adjaye Frimpong Christian Kofi Gyasi-Sarpong Department of Surgery School of Medicine and Dentistry Kwame Nkrumah University of Science and Technology Kumasi Ghana Department of Surgery Komfo Anokye Teaching Hospital Kumasi Ghana Department of Surgery School of Medical Sciences University of Cape Coast Cape Coast Ghana Department of Radiology School of Medicine and Dentistry Kwame Nkrumah University of Science and Technology Kumasi Ghana

Introduction: Urethroplasty remains the gold standard for the management of urethral stricture. However, the treatment of stricture disease in the elderly tends to be less invasive due to the presumption that they might not be able to stand long hours of surgery and might have higher rates of recurrence due to poor wound healing from microangiopathy. We present our experience with the outcomes of urethroplasty among elderly men seen at the Komfo Anokye Teaching Hospital from January 2012 to December 2021. Methods: This was a retrospective review of data captured in the urology database on all patients 65 years and above who underwent urethroplasty at the hospital over the study period. Data was obtained on patients’ demographics, stricture characteristics, urethroplasty technique, and outcome. A successful outcome was defined as peak flow rate > 15 mls/s, a patent urethra on retrograde urethrogram, patient satisfaction with urine stream, or restoration of the normal stream of urine with only one attempt at urethral calibration or internal urethrotomy postoperatively. Data was analyzed using PASW Statistics for Windows, Version 18.0. Results: Overall, 43 urethroplasties were done over the study period in elderly men. The age range was 65 to 87 years. The commonest aetiology was catheterization (62.79%) followed by urethritis (32.56%). Stricture length ranged from 0.5 cm to 16 cm with a mean of 3.93 cm. Most patients (60.46%) had bulbar urethral strictures. The repair methods employed were anastomotic urethroplasty (62.80%), fasciocutaneous flap (FCF) ventral onlay (13.95%), buccal mucosa graft (BMG) ventral onlay urethroplasty (4.65%), and staged urethroplasty (4.65%). Three of the patients (6.98%) had a combination of anastomotic and tissue transfer urethroplasty. The overall success rate was 88.37%. Complications included three surgical site infections, two urethral diverticula and one glans dehiscence. Conclusion: Elderly men tolerate urethroplasty well and the pr

关键词： Urethral Stricture Elderly Men Urethroplasty Surgical Techniques

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The dawn and rise of antimony use in the southern Caucasus

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Science China Earth Sciences 2022年第11期65卷 2037-2056页

作者： Sarah DILLIS patrick DEGRYSE Department of Earth and Environmental Sciences Katholieke Universiteit LeuvenCelestjnenlaan 200 EHeverlee 3001Belgium Faculty of Archaeology Leiden UniversityEinsteinweg 2Leiden 2333 CCThe Netherlands

Antimony(Sb)was utilised over several millennia as the prime material to opacify or decolour glass and glazes,as well as an accompanying element in copper(Cu)*** antimony objects are rare,and mostly confined to Chalcolithic Central Italy and to the first millennia BCE in the southern *** innovation of antimony use in metallurgy seems to be confined to the southern Caucasus,and the invention of it might be even more specifically situated in the Great *** knowledge of mining set the pathway for the initial stage of antimonial copper alloys in the first half of the third millennium BCE and for metallic antimony ornaments in the second half of the third millennium ***,the first major expansion of antimony in the metallurgy of the Racha-Lechkumi district in the southern Caucasus(present-day Georgia)started around 1700 BCE,while its spreading in glassmaking occurred in the Late Bronze Age(LBA).Explanations that place antimony adoption within its broader social context are favoured over those that consider material or geological properties in isolation.A recurring theme is the importance of comparative analysis,both geographically and between the different pyrotechnologies,including the precious metals and glass industries,to explore how social,political,climatic and economic conditions affected adoption and innovation *** these factors are considered to explain why the extraction of antimony blossomed in the Late Bronze Age in the southern Caucasus and to reconstruct a framework of exploitation,distribution/trade and use of antimony in the Caucasus and its neighbouring regions in the south and east.

关键词： Antimony Caucasus Metallurgy Glass Gold

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Advances on numerical and experimental investigation of ship roll damping

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水动力学研究与进展B辑:英文版 2023年第3期35卷 431-448页

作者： patrick Sumislawski Moustafa Abdel-Maksoud Institute for Fluid Dynamics and Ship Theory Hamburg University of Technology (TUHH) Hamburg Germany

This paper presents recent developments towards efficient and reliable methods for roll damping estimation based on numerical simulations as well as model tests using the harmonic excited roll motion(HERM)technique.A newly designed automatic roll damping estimation procedure shows the advantage of a just-in-time post processing of experimental measurement ***-time analysis of the measured roll damping values permits a considerable shortening of the test ***,a large number of investigations can be carried out with relatively manageable effort in order to determine the roll damping behavior of different keel configurations or at operating conditions,e.g.,different sized keels or Froude *** addition,HERM measurement method is applied to investigate the memory *** this purpose,different excitation schemes are introduced and the results are ***,a study of the scale effect on the roll damping properties is conducted,in which experimental and numerical investigations are performed for two scales of a ship ***,a method is developed that significantly reduces the effort of Reynolds average Navier-Stokes(RANS)-based simulations of roll *** reduction of simulation time is achieved by introducing an artificial *** obtained results show that the developed method is very well applicable for numerical as well as in experimental *** the model tests using HERM technique,the model is free and the rudder is used to keep the straight-ahead *** analysis of the numerical and experimental results shows that the influence of the rudder induced force and moment during HERM tests is not negligible and the contribution of the rudder must be taken into account by estimating the roll ***,a new concept is developed to investigate the parametric roll behavior of ships,which allows neglecting the consideration of the complex modelling of free surface waves in the *** the RAN

关键词： Roll damping harmonic excited roll motion rudder HERM experimental fluid dynamics(EFD) CFD

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Prenatal multiple micronutrient-fortified balanced energy-protein supplementation and newborn telomere length and mitochondrial DNA content: a randomized controlled efficacy trial in rural Burkina Faso

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Food Science and Human Wellness 2024年

作者： Giles T.Hanley-Cook Yuri Bastos-Moreira Dries S.Martens Trenton Dailey-Chwalibóg Laeticia Celine Toe Brenda de Kok Lionel Ouédraogo Alemayehu Argaw Kokeb Tesfamariam patrick Kolsteren Lieven Huybregts Tim S.Nawrot Sarah De Saeger Marthe De Boevre Carl Lachat Department of Food Technology Safety and Health Faculty of Bioscience Engineering Ghent University Center of Excellence in Mycotoxicology and Public Health MYTOXSOUTH~(?) Coordination Unit Faculty of Pharmaceutical Sciences Ghent University Centre for Environmental Sciences Hasselt University Unité Nutrition et Maladies Métaboliques Institut de Recherche en Sciences de la Santé (IRSS) Centre Muraz Center of Excellence in Mycotoxicology and Public Health MYTOXSOUTH? Coordination Unit Faculty of Pharmaceutical Sciences Ghent University Nutrition Diets and Health Unit Department of Food and Nutrition Policy International Food Policy Research Institute (IFPRI) Department of Public Health & Primary Care University of Leuven Department of Biotechnology and Food Technology Faculty of Science University of Johannesburg Doornfontein Campus

Background: Evidence regarding the effectiveness of prenatal nutritional supplements has mainly considered anthropometric pregnancy outcomes. The effect on markers of health and disease， such as offspring telomere length (TL) and mitochondrial DNA content (mtDNAc) is unknown. Objectives: We assessed the efficacy of maternal multiple micronutrient (MMN)-fortified balanced-energy protein (BEP) and iron-folic acid (IFA) supplementation on newborn TL as a secondary outcome and mtDNAc as a non-declared outcome. Design: We conducted a randomized controlled trial in rural Burkina Faso， among pregnant females (15-40 years old) enrolled at 0.05) by adjusting the regression models for potential prognostic factors of study outcomes at enrollment. Exploratory analyses indicated higher， but non-significantly different mtDNAc among children born either small-for-gestational age， low birthweight， or preterm. Conclusions: Newborns from mothers who received daily nutritional supplements across gestation did not have different relative TL or mtDNAc.

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Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

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Open Journal of Obstetrics and Gynecology 2024年第5期14卷 693-704页

作者： Leandro Santos de Araujo Resende Francine Vilela de Amorim Miguel Soares Conceição Rodrigo Menezes Jales patrick Nunes Pereira Luis Otávio Sarian Glauco Baiocchi Sophie Derchain Agnaldo Lopes da Silva Filho Department of Gynecology and Obstetrics Botucatu Medical School S&#227o Paulo State University UNESP S&#227o Paulo Brazil Department of Health Sciences University of Sao Francisco S&#227o Paulo Brazil Department of Obstetrics and Gynecology School of Medical Science State University of Campinas (UNICAMP) Campinas Brazil Department of Gynecologic Oncology AC Camargo Cancer Center Sao Paulo Brazil Department of Gynecology and Obstetrics School of Medicine of the Federal University of Minas Gerais Belo Horizonte Brazil

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

关键词： Cervical Cancer Sarcopenia Anemia Chemoradiotherapy

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Surface nanobubble characterization and its enhancement mechanisms for fine-particle flotation:A review

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International Journal of Minerals,Metallurgy and Materials 2022年第4期29卷 727-738页

作者： Fangyuan Ma patrick Zhang Dongping Tao School of Resources and Environmental Engineering Shandong University of TechnologyZibo 255049China Florida Industrial and Phosphate Research Institute Florida Polytechnic UniversityFlorida 33830USA

Froth flotation is often used for fine-particle separation,but its process efficiency rapidly decreases with decreasing particle *** efficient separation of ultrafine particles(UFPs)has been a major challenge in the mineral processing field for many *** recent years,the use of surface nanobubbles in the flotation process has been recognized as an effective approach for enhancing the recovery of *** with traditional macrobubbles,nanobubbles possess unique surface and bulk characteristics,and their effects on the UFP flotation behavior have been a topic of intensive *** review article is focused on the studies on various unique characteristics of nanobubbles and their mechanisms of enhancing the UFP *** purpose of this article is to summarize the major achievements on the two topics and pinpoint future research needs for a better understanding of the fundamentals of surface nanobubble flotation and developing more feasible and efficient processes for fine and UFPs.

关键词： surface nanobubbles characterization flotation ultrafine particles high-efficiency separation

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Optimal trajectory design accounting for the stabilization of linear time-varying error dynamics

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Chinese Journal of Aeronautics 2022年第7期35卷 55-66页

作者： patrick PIPREK Haichao HONG Florian HOLZAPFEL Institute of Flight System Dynamics Technical University of MunichGarching D-85748Germany

This study is dedicated to the development of a direct optimal control-based algorithm for trajectory optimization problems that accounts for the closed-loop stability of the trajectory tracking error dynamics already during the ***,the trajectory is designed such that the Linear Time-Varying(LTV)dynamic system,describing the controller’s error dynamics,is stable,while additionally the desired optimality criterion is optimized and all enforced constraints on the trajectory are *** is achieved by means of a Lyapunov stability analysis of the LTV dynamics within the optimization problem using a time-dependent,quadratic Lyapunov function *** care is taken with regard to ensuring the correct definiteness of the ensuing matrices within the Lyapunov stability analysis,specifically considering a numerically stable formulation of these in the numerical *** developed algorithm is applied to a trajectory design problem for which the LTV system is part of the path-following error dynamics,which is required to be *** main benefit of the proposed scheme in this context is that the designed trajectory trades-off the required stability and robustness properties of the LTV dynamics with the optimality of the trajectory already at the design phase and thus,does not produce unstable optimal trajectories the system must follow in the real application.

关键词： LTV error dynamics LTV stability Optimal control-based LTV stabilization Path-following error controller Trajectory generation Trajectory optimization

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C1C2 Wiring and Posttraumatic Atlantoaxial Dislocation: An Effective and Cheap Surgical Procedure in a Developing Country

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Surgical Science 2024年第5期15卷 357-370页

作者： Ibrahim Dao Massimiliano Visocchi Salah Sow John Jabang Ousmane Ouattara Astride Somda Abdoulaye Sanou Elie Dibloni Nassoum Arsène Tossou Narcisse Ouedraogo Frédéric Bako Massadiami Soulama Malick Diallo patrick Wendpouiré Hamed Dakouré Department of Neurosurgery University Hospital Souro Sanou Nazi Boni University Bobo Dioulasso Burkina Faso High Institute of Health Sciences Nazi Boni University Bobo Dioulasso Burkina Faso Military Hospital Colonel Major Tanguet Ouattara Bobo Dioulasso Burkina Faso Institute of Neurosurgery Craniovertebral Junction Surgery Unit School of Medicine Catholic University Rome Italy Department of Radiology and Medical Imaging University Hospital Yalgado Ouedraogo Joseph Ki-Zerbo University Ouagadougou Burkina Faso Department of Neurosurgery (Unit) Edward Francis Small Teaching Hospital Banjul Gambia Department of Neurosurgery University Hospital Yalgado Ouedraogo Joseph Ki-Zerbo University Ouagadougou Burkina Faso Department of Neurosurgery Military Hospital Capitaine Halassane Coulibaly Ouagadougou Burkina Faso Department of Orthopedic Surgery University Hospital Souro Sanou Nazi Boni University Bobo Dioulasso Burkina Faso

Objectives: Atlantoaxial dislocation remains a rare and serious condition with a high preoperative and postoperative morbidity and mortality. Its successful surgical management is still challenging and gratifying for neurosurgeons. Several technics have been described such as wiring, trans articular screwing, C1C2 screwing with plate and screw introduced by Goel et al., and modified by insertion of polyaxially screw and rod many years later by Harms. Unavailability and expensiveness of upper cervical spine instrumentation device led us to C1C2 Wiring resulting in a good outcome. Finally, a quadriplegic patient with a more comfortable financial condition had ordered devices from abroad and benefit for Goel and Harms screwing technique and improved dramatically from ASIA A to ASIA E. Material and methods: This is a retrospective study of patients managed in our department by a same neurosurgeon from January 2019 to April 2024. Results: We defined 6 men and 1 woman with an average age of 33 years. Unrestrained driver in a rollover motor vehicle accident was most common. Only one patient was neurologically intact on admission. Neurovegetative disorders were noticed in one patient. Dislocation was associated to a fracture of the dens in two patients. Three patients have been successfully operated with remarkable outcome, mostly from ASIA A to E. Conclusion: C1C2 dislocation is a serious condition and C1C2 Wiring represents an effective and cheaper technic. Therefore, this technic should deserve consideration above all in low incomes countries when screwing devices are not available. Seatbelt should be demanded for motor vehicle drivers and passengers.

关键词： Superior Cervical Spine Dislocation Fracture Wiring Screwing Neurovegetative Disorders

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