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Using Pharmacokinetic Modeling and Electronic Health record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates

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Congenital Heart Disease 2023年第3期18卷 295-313页

作者： Henry P.Foote Huali Wu Stephen J.Balevic Elizabeth J.Thompson Kevin D.Hill Eric M.Graham Christoph P.Hornik karan r.kumar Department of Pediatrics Duke UniversityDurhamUSA Duke Clinical research Institute DurhamUSA Department of Pediatrics Medical University of South CarolinaCharlestonUSA

Background:Infants undergoing cardiac surgery with cardiopulmonary bypass(CPB)frequently receive intraoperative methylprednisolone(MP)to suppress CPB-related inflammation;however,the optimal dosing strategy and efficacy of MP remain ***:We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014–2017 at our *** combined real-world dosing data from the electronic health record(EHr)and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration(Cmax)and area under the concentration-time curve for 24 h(AUC24)for MP and the inflammatory cytokines interleukin-6(IL-6)and interleukin-10(IL-10).We evaluated the relationships between post-operative,safety,and other clinical outcomes obtained from the EHr with each predicted exposure using non-parametric ***:A total of 142 infants with median post-natal age 8(interquartile range[IQr]:5,37)days received a total dose of 30(19,49)mg/kg of ***(8%)died,37(26%)met the composite post-operative outcome,114(80%)met the composite safety outcome,and 23(16%)had a major *** median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major *** median Cmax and AUC24 MP exposure was significantly higher for infants requiring *** exposure was associated with death or other safety ***:Pro-inflammatory IL-6,but not MP exposure,was associated with post-operative organ dysfunction,suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical *** study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

关键词： Neonates cardiopulmonary bypass methylprednisolone exposure

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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

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Oncology research 2024年第5期32卷 877-897页

作者： karan WADHWA PAYAL CHAUHAN SHOBHIT kumar rAKESH PAHWA rAVINDEr VErMA rAJAT GOYAL GOVIND SINGH ArCHANA SHArMA NEHA rAO DEEPAK KAUSHIK Department of Pharmaceutical Sciences Maharshi Dayanand UniversityRohtak124001India Department of Pharmaceutical Technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of Pharmaceutical Sciences Kurukshetra UniversityKurukshetra136119India Department of Pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi Pharmaceutical Sciences and research University(DIPSAr) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive *** high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the ***:recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation ***:relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several ***:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM *** of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

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Finite Deformation, Finite Strain Nonlinear Dynamics and Dynamic Bifurcation in TVE Solids with rheology

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Applied Mathematics 2024年第1期15卷 108-168页

作者： karan S. Surana Sri Sai Charan Mathi Department of Mechanical Engineering University of Kansas Lawrence US

This paper presents a mathematical model consisting of conservation and balance laws (CBL) of classical continuum mechanics (CCM) and ordered rate constitutive theories in Lagrangian description derived using entropy inequality and the representation theorem for thermoviscoelastic solids (TVES) with rheology. The CBL and the constitutive theories take into account finite deformation and finite strain deformation physics and are based on contravariant deviatoric second Piola-Kirchhoff stress tensor and its work conjugate covariant Green’s strain tensor and their material derivatives of up to order m and n respectively. All published works on nonlinear dynamics of TVES with rheology are mostly based on phenomenological mathematical models. In rare instances, some aspects of CBL are used but are incorrectly altered to obtain mass, stiffness and damping matrices using space-time decoupled approaches. In the work presented in this paper, we show that this is not possible using CBL of CCM for TVES with rheology. Thus, the mathematical models used currently in the published works are not the correct description of the physics of nonlinear dynamics of TVES with rheology. The mathematical model used in the present work is strictly based on the CBL of CCM and is thermodynamically and mathematically consistent and the space-time coupled finite element methodology used in this work is unconditionally stable and provides solutions with desired accuracy and is ideally suited for nonlinear dynamics of TVES with memory. The work in this paper is the first presentation of a mathematical model strictly based on CBL of CCM and the solution of the mathematical model is obtained using unconditionally stable space-time coupled computational methodology that provides control over the errors in the evolution. Both space-time coupled and space-time decoupled finite element formulations are considered for obtaining solutions of the IVPs described by the mathematical model and are presented i

关键词： Thermoviscoelasticity rheology Memory Finite Strain Finite Deformation Nonlinear Dynamics Dynamic Bifurcation Ordered rate Theories

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Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma

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World Journal of Hepatology 2024年第3期16卷 393-404页

作者： Andrew Scott deLemos Jing Zhao Milin Patel Banks Kooken karan Mathur Hieu Minh Nguyen Areej Mazhar Maggie McCarter Heather Burney Carla Kettler Naga Chalasani Samer Gawrieh Department of Medicine Atrium HealthCharlotteNC 28204United States Center for Outcomes research and Evaluation Atrium HealthCharlotteNC 28204United States Department of Medicine Indiana University School of MedicineIndianapolisIN 46202United States Center for Health System Sciences(CHASSIS) Atrium HealthCharlotteNC 28204United States Department of Medicine Northwestern University Feinberg School of MedicineChicagoIL 60611United States Department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisIN 46202United States Department of Gastroenterology and Hepatology Indiana University School of MedicineIndianapolisIN 46202United States

BACKGrOUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its ***,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival *** is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight *** To explore the relationship between BMI and survival in patients with cirrhosis and *** This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical *** and tumor characteristics were extracted manually from medical records of each institutions'cancer *** were stratified according to BMI classes:rweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI *** performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and *** A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as *** three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population *** each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),*** patients with a BMIre included in the lean *** the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were *** three BMI classes did not differ by age,MELD,or Child-Pugh *** hepatitis C was the dominant etiology in lea

关键词： Hepatocellular carcinoma Cirrhosis Obesity Body mass index class Sarcopenia Chronic hepatitis C

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Fresh or aged:Short time anodization of titanium to understand the influence of electrolyte aging on titania nanopores

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Journal of Materials Science & Technology 2022年第24期119卷 245-256页

作者： Tianqi Guo Saso Ivanovski karan Gulati The University of Queensland School of DentistryHerston QLD 4006Australia

Electrochemical anodization(EA)is a simple and cost-effective technique to fabricate controlled nanostructures on Ti substrates,such as TiO_(2)nanotubes and *** aging of organic EA electrolytes(repeated EA using non-target Ti before EA of target Ti)is recognized to influence the characteristics of the anodized ***,there is limited information about how surface topography and electrolyte aging dictate the formation and characteristics of the anodized *** the current study,short-time EA(starting at 10 s)of micro-machined Ti substrates was performed with electrolytes of various ages(fresh/unused,15 h aged and 30 h aged),followed by evaluation of the TiO_(2)nanopores(TNPs)characteristics in terms of topography,chemistry,stability and protein *** results showed that aligned TNPs were obtained earlier(120 s)with fresh electrolyte as compared to the aged electrolyte EA(600 s).Interestingly,TNPs fabricated using fresh electrolyte(at lower EA times)showed favorable wettability,protein adhesion capacity and mechanical properties compared with aged electrolyte *** findings of the study demonstrate how nanopore formation differs between fresh and aged electrolytes when performing EA of micro-machined Ti,which provides an improved understanding of electrolyte aging and its influence on anodized nanostructures.

关键词： Titanium Titania nanopores Electrochemical anodization Electrolyte aging Surface modification

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