Comparative Outcome Data Using Different Techniques for Posterior Lumbar Fusion: A Large Single-Center Study

Lewis Daniel,Marya Shivan,Carrasco Roberto,Sabou Silviu,Leach John 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.5

Study Design: Retrospective single-center study.Purpose: This study aims to evaluate perioperative and intermediate-term clinical outcomes of patients undergoing different lumbar fusion techniques.Overview of Literature: Various open and minimally invasive techniques for lumbar fusion are available, but previous studies comparing lumbar fusion techniques have heterogeneous data, making interpretation challenging.Methods: Between 2011 and 2018, data from 447 consecutive patients undergoing one/two-level lumbar fusion were analyzed. Posterior lumbar interbody fusion (PLIF) with bilateral muscle strip or Wiltse approach, open transforaminal lumbar interbody fusion (TLIF) and minimally invasive TLIF, and posterolateral fusion only were among the surgical techniques used. Core outcomes measure index (COMI) questionnaires were distributed before surgery and at 3 months, 1 year, and 2 years postoperatively to establish patient selfreported outcome measures. Demographic data (age, gender, and body mass index [BMI]) for each patient were also collected in addition to surgical indication, previous operative history, perioperative outcomes, and complications, and whether later revision surgery was required. Pearson’s chi-square test, Kruskal-Wallis test, repeated measure mixed-effects models, and ordinal logistic regression were used for statistical analysis.Results: Postoperative COMI scores improved across all procedures compared with pre-surgery (<i>p</i><0.001). There was no significant difference between different postoperative COMI scores. Significant predictors of higher postoperative COMI score included higher pretreatment COMI score (<i>p</i>≤0.001), previous surgery (<i>p</i>≤0.04), younger age (<i>p</i>≤0.05), higher BMI (<i>p</i>≤0.005), and the indications of lytic spondylolisthesis (<i>p</i>=0.02) and degenerative disc disease (<i>p</i><0.001). Patients undergoing minimally invasive TLIF had a significantly shorter post-surgery stay than patients undergoing open PLIF (Kruskal-Wallis test, <i>p</i>=0.03).Conclusions: At 2 years postoperatively, there was no significant difference in clinical outcomes between open and minimally invasive techniques. These findings suggest that the main determinant of surgical approach should be surgeon preference and training.

Effect of Acute Physical Interventions on Pathophysiology and Recovery After Spinal Cord Injury: A Comprehensive Review of the Literature

Nicholle E. Lewis,Troy Q. Tabarestani,Brianna R. Cellini,Nina Zhang,Eric J. Marrotte,Haichen Wang,Daniel T. Laskowitz,Muhammad M. Abd-El-Barr,Timothy D. Faw 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

Physical rehabilitation is essential for enhancing recovery in individuals with spinal cord injury (SCI); however, aside from early surgical intervention and hemodynamic management, there are no proven interventions for promoting recovery in the acute phase. In general, early rehabilitation is considered beneficial, but optimal parameters and potential contraindications for implementing rehabilitation at very early time points are unclear. Moreover, clinical trials to date are limited to studies initiating rehabilitation 2 weeks after injury and later. To address these gaps, this article reviews the preclinical literature on physical interventions initiated within the first 8 days postinjury. Effects of early rehabilitation on molecular and structural nervous system changes, behavioral function, and body systems are considered. Most studies utilized treadmill or cycle training as the primary intervention. Treadmill training initiated within the first 3 days and terminated by 1 week after injury worsened autonomic function, inflammation, and locomotor outcomes, while swim training during this period increased microvascular dysfunction. In contrast, lower-intensity rehabilitation such as reach training, ladder training, or voluntary wheel or ball training showed benefits when implemented during the first 3 days. Rehabilitation initiated at 4 days postinjury was also associated with enhanced motor recovery. Cycling appears to have the greatest risk-benefit ratio; however, the effects of cycle training in the first 3 days were not investigated. Overall, research suggests that lower intensity or voluntary rehabilitation during the hyperacute phase is more appropriate until at least 4 days postinjury, at which point higher-intensity activity becomes safer and more beneficial for recovery.

Bioinspired Hydrogels to Engineer Cancer Microenvironments

Park, Kyung Min,Lewis, Daniel,Gerecht, Sharon Annual Reviews 2017 Annual review of biomedical engineering Vol. No.

<P>Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.</P>

Thermodynamic Analysis of Nickel(II) and Zinc(II) Adsorption to Biochar

Alam, Md. Samrat,Gorman-Lewis, Drew,Chen, Ning,Flynn, Shannon L.,Ok, Yong Sik,Konhauser, Kurt O.,Alessi, Daniel S. American Chemical Society 2018 Environmental science & technology Vol.52 No.11

<P>While numerous studies have investigated metal uptake from solution by biochar, few of these have developed a mechanistic understanding of the adsorption reactions that occur at the biochar surface. In this study, we explore a combined modeling and spectroscopic approach for the first time to describe the molecular level adsorption of Ni(II) and Zn(II) to five types of biochar. Following thorough characterization, potentiometric titrations were carried out to measure the proton (H<SUP>+</SUP>) reactivity of each biochar, and the data was used to develop protonation models. Surface complexation modeling (SCM) supported by synchrotron-based extended X-ray absorption fine structure (EXAFS) was then used to gain insights into the molecular scale metal-biochar surface reactions. The SCM approach was combined with isothermal titration calorimetry (ITC) data to determine the thermodynamic driving forces of metal adsorption. Our results show that the reactivity of biochar toward Ni(II) and Zn(II) directly relates to the site densities of biochar. EXAFS along with FT-IR analyses, suggest that Ni(II) and Zn(II) adsorption occurred primarily through proton-active carboxyl (−COOH) and hydroxyl (−OH) functional groups on the biochar surface. SCM-ITC analyses revealed that the enthalpies of protonation are exothermic and Ni(II) and Zn(II) complexes with biochar surface are slightly exothermic to slightly endothermic. The results obtained from these combined approaches contribute to the better understanding of molecular scale metal adsorption onto the biochar surface, and will facilitate the further development of thermodynamics-based, predictive approaches to biochar removal of metals from contaminated water.</P> [FIG OMISSION]</BR>

Blueberry Intake Alters Skeletal Muscle and Adipose Tissue Peroxisome Proliferator-Activated Receptor Activity and Reduces Insulin Resistance in Obese Rats

E. Mitchell Seymour,Ignasia I. Tanone,Daniel E. Urcuyo-Llanes,Sarah K. Lewis,Ara Kirakosyan,Michael G. Kondoleon,Peter B. Kaufman,Steven F. Bolling 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.12

Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferatoractivated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal)containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass,increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesityprone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.

Surgical Considerations to Improve Recovery in Acute Spinal Cord Injury

Troy Q. Tabarestani,Nicholle E. Lewis,Margot Kelly-Hedrick,Nina Zhang,Brianna R. Cellini,Eric J. Marrotte,Theresa Williamson,Haichen Wang,Daniel T. Laskowitz,Timothy D. Faw,Muhammad M. Abd-El-Barr 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

Acute traumatic spinal cord injury (SCI) can be a devastating and costly event for individuals, their families, and the health system as a whole. Prognosis is heavily dependent on the physical extent of the injury and the severity of neurological dysfunction. If not treated urgently, individuals can suffer exacerbated secondary injury cascades that may increase tissue injury and limit recovery. Initial recognition and rapid treatment of acute SCI are vital to limiting secondary injury, reducing morbidity, and providing the best chance of functional recovery. This article aims to review the pathophysiology of SCI and the most up-todate management of the acute traumatic SCI, specifically examining the modern approaches to surgical treatments along with the ethical limitations of research in this field.

Regular Tart Cherry Intake Alters Abdominal Adiposity, Adipose Gene Transcription, and Inflammation in Obesity-Prone Rats Fed a High Fat Diet

E.M. Seymour,Sarah K. Lewis,Daniel E. Urcuyo-Llanes,Ignasia I. Tanone,Ara Kirakosyan,Peter B. Kaufman,Steven F. Bolling 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5

Obesity, systemic inflammation, and hyperlipidemia are among the components of metabolic syndrome, a spectrum of phenotypes that can precede the development of type 2 diabetes and cardiovascular disease. Animal studies show that intake of anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the activity of tissue peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism and inflammation. However, it is unknown if physiologically relevant, anthocyanin-containing whole foods confer similar effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich tart cherries was tested in the Zucker fatty rat model of obesity and metabolic syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and macronutrient-matched control diet. Tart cherry intake was associated with reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal) weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression, and plasma IL-6 and TNF-α. Tart cherry diet also increased retroperitoneal fat PPAR-α and PPAR-γ mRNA (P=.12), decreased IL-6 and TNF-α mRNA, and decreased nuclear factor κB activity. In conclusion, in at-risk obese rats fed a high fat diet, physiologically relevant tart cherry consumption reduced several phenotypes of metabolic syndrome and reduced both systemic and local inflammation. Tart cherries may reduce the degree or trajectory of metabolic syndrome, thereby reducing risk for the development of type 2 diabetes and heart disease.

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC)

Bergmeijer, Thomas O.,Reny, Jean-Luc,Pakyz, Ruth E.,Gong, Li,Lewis, Joshua P.,Kim, Eun-Young,Aradi, Daniel,Fernandez-Cadenas, Israel,Horenstein, Richard B.,Lee, Ming Ta Michael,Whaley, Ryan M.,Montane Elsevier 2018 American Heart Journal Vol.198 No.-

<P><B>Rationale</B></P> <P>The P2Y<SUB>12</SUB> receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. <I>CYP2C19</I> polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response.</P> <P><B>Study design</B></P> <P>Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies.</P> <P><B>Results</B></P> <P>In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y<SUB>12</SUB> assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between <I>CYP2C19</I>*2 and platelet reactivity (<I>P</I> value=5.1 × 10<SUP>−40</SUP>).</P> <P><B>Conclusion</B></P> <P>The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.</P>

Genetic features associated with <SUP>18</SUP>F-FDG uptake in intrahepatic cholangiocarcinoma

Keun Soo Ahn,Koo Jeong Kang,Yong Hoon Kim,Tae-Seok Kim,Bong-Il Song,Hae Won Kim,Daniel O’Brien,Lewis R. Roberts,Jeong Woo Lee,Kyoung Sook Won 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.4

Purpose: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on <SUP>18</SUP>F-fluorodeoxyglucose (<SUP>18</SUP>F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. Methods: We performed RNA sequencing of 22 cases iCCA who underwent preoperative <SUP>18</SUP>F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. Results: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. Conclusion: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.

Prognostic Subclasses of Intrahepatic Cholangiocarcinoma by Integrative Molecular - Clinical Analysis and Potential Targeted Approach

( Keun Soo Ahn ),( Koo Jeong Kang ),( Yu Na Kang ),( Yong Hoon Kim ),( Tae-seok Kim ),( Daniel O’ Brien ),( Lewis R Roberts ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Although molecular characterization of intrahepatic cholangiocarcinoma(CCA) has been studied recently, integrative analysis between molecular and clinical characterization has not been established yet. We analyzed RNA sequencing data with annotated clinical data for clarifying genomic features of intrahepatic CCA, molecular specific clinical features and evaluating therapeutic potential based on molecular subtypes. Methods: We performed next generation RNA sequencing of 30 surgically resected intrahepatic CCA from Korean patients. RNA expression, variants and fusions were analyzed with clinical, pathologic features. RNA sequences from 32 intrahepatic CCA resected from USA were used for validation. Results: Patients were classified into 2 subclasses based on unsupervised clustering, which showed a significant difference 5- year survival. The validation cohort of USA data also revealed two subclasses with significant differences in survival. Two subclasses had different clinical and pathologic features for higher CEA and CA19-9 levels, underlying cholangitis and bile duct type pathology in the poor prognostic subclass and more frequent hepatitis and cholangiolar type of pathology in better prognostic subclass. On pathway analysis, liver related signatures were enriched in better prognosis subclass. In poor prognosis subclass, inflammation related pathways were enriched and KRAS mutation was more frequent. Cholangiocarcinoma cell lines which have similar gene expression pattern with better prognosis subclass were sensitive to gemcitabine. Conclusions: Two molecular subtypes of intrahepatic CCA with distinct clinical, biological and prognostic differences were identified. With clinical and pathological characteristics, molecular subtypes can be predicted and different signaling pathways of subtypes may lead to more rational targeted approaches to treatment.