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Analysing the outcome of surgery for chronic Achilles tendinopathy over the last 50 years

World Journal of Orthopedics 2015年第6期6卷 491-497页

作者： Wasim S Khan seema malvankar Jagmeet S Bhamra Ioannis Pengas University College London Institute of Orthopaedics and Musculoskeletal Science Royal National Orthopaedic Hospital

AIM: To determine an association between when the study was performed, the robustness of the study and the outcomes for insertional and non-insertional Achilles tendinopathy surgery. METHODS: We performed a systematic review in accordance with the PRISMA guidelines to assess the methodology of studies investigating the outcome of surgery in chronic Achilles tendinopathy over the last 50 years to identify any trends that would account for the variable results. The Coleman Methodology Scores were correlated with the reported percentage success rates and with the publication year to determine any trends using Pearson's correlation. RESULTS: We identified 62 studies published between 1964 and 2014 reporting on a total of 2923 surgically treated Achilles tendinopathies. The average followup time was 40 mo(range 5-204 mo), and the mean reported success rate was 83.5%(range 36%-100%). The Coleman Methodology Scores were highly reproducible(r = 0.99, P < 0.01), with a mean of 40.1(SD 18.9, range 2-79). We found a negative correlation between reported success rate and overall methodology scores(r =-0.40, P < 0.001), and a positive correlation between year of publication and overall methodology scores(r = 0.46, P < 0.001). CONCLUSION: We conclude that although the success rate of surgery for chronic Acilles tendinopathy described in the literature has fallen over the last 50 years, this is probably due to a more rigorous methodology of the studies.

关键词： Achilles tendon Surgery Methodology Outcome Tendinopathy

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Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer’s disease mouse model

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Translational Neurodegeneration 2023年第1期12卷 70-89页

作者： Carolyn Tallon Benjamin J.Bell Medhinee M.malvankar Pragney Deme Carlos Nogueras-Ortiz Erden Eren Ajit G.Thomas Kristen R.Hollinger Arindom Pal Maja Mustapic Meixiang Huang Kaleem Coleman Tawnjerae R.Joe Rana Rais Norman J.Haughey Dimitrios Kapogiannis Barbara S.Slusher Johns Hopkins Drug Discovery Johns Hopkins University School of MedicineBaltimoreMD 21205USA Neurology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Cell Biology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Oncology Johns Hopkins University School of MedicineBaltimoreMD 21205USA Medicine Johns Hopkins University School of MedicineBaltimoreMD 21205USA Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD 21205USA Psychiatry and Behavioral Science Johns Hopkins University School of Medicine855 N.Wolfe StreetRangos 278BaltimoreMD 21205USA Intramural Research Program Laboratory of Clinical InvestigationNational Institute on AgingNational Institutes of Health251 Bayview BlvdSte 8C228BaltimoreMD 21224USA Johns Hopkins University School of Medicine 600 N.Wolfe StreetPathology 517BaltimoreMD 21287USA

Background Cognitive decline in Alzheimer’s disease(AD)is associated with hyperphosphorylated tau(pTau)propagation between neurons along synaptically connected networks,in part via extracellular vesicles(EVs).EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of *** report,for the first time,that human tau expression elevates brain ceramides and nSMase2 *** To determine the therapeutic benefit of inhibiting this elevation,we evaluated PDDC,the first potent,selective,orally bioavailable,and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse ***,we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus(AAV)encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the *** contralateral transfer of the double mutant human tau to the dentate gyrus was *** examined ceramide levels,histopathological changes,and pTau content within EVs isolated from the mouse *** Similar to human AD,the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity;both were completely normalized by PDDC *** PS19 mice also exhibited elevated tau immunostaining,thinning of hippocampal neuronal cell layers,increased mossy fiber synaptophysin immunostaining,and glial activation,all of which were pathologic features of human *** treatment reduced these *** plasma of PDDC-treated PS19 mice had reduced levels of neuronal-and microglial-derived EVs,the former carrying lower pTau levels,compared to untreated *** the tau propagation model,PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral *** PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity,leading to the slo

关键词： Alzheimer’s disease Extracellular vesicles Neutral sphingomyelinase 2 Tau Ceramide

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