A Computed Tomography Analysis of the Success of Spinal Fusion Using Ultra-Low Dose (0.7 mg per Facet) of Recombinant Human Bone Morphogenetic Protein 2 in Multilevel Adult Degenerative Spinal Deformity Surgery

Gabriel Liu,Jun Hao Tan,Changwei Yang,John Ruiz,Hee-Kit Wong 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.6

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28–72 years) were examined. Each patient received a total dose of 12 mg with an average dose of 0.69±0.2 mg (0.42–1 mg) per single FF and 1.38±0.44 mg (0.85–2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (κ=0.95) and 100% vs. 100% IBF, respectively (κ=1). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (κ=0.96). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1–2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of 32.8±6.3, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of 4.7±2.1, and physical component summary improved by an average of 10.5±2.1. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%–98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

Thoracolumbar Injury Classification and Severity Score Is Predictive of Perioperative Adverse Events in Operatively Treated Thoracic and Lumbar Fractures

Liu Gabriel Ka-Po,Tan Jiong Hao,Kong Jun Cheong,Tan Yong Hao Joel,Kumar Nishant,Liang Shen,Shawn Seah Jing Sheng,Ting Chiu Shi,Lim Lau Leok,Dennis Hey Hwee Weng,Kumar Naresh,Thambiah Joseph,Wong Hee-K 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.6

Study Design: A retrospective cohort study of patients with surgically treated thoracolumbar fractures.Purpose: This study aimed to describe the incidence of adverse events (AEs) after surgical stabilization of thoracolumbar spine injuries and to identify predictive factors for the occurrence of AEs. Overview of Literature: Thoracolumbar spine fractures are frequently present in patients with blunt trauma and are associated with significant morbidity. AEs can occur due to the initial spinal injury or secondary to surgical treatment. There is a lack of emphasis in the literature on the AEs that can occur after operative management of thoracolumbar fractures.Methods: We performed a retrospective review of 199 patients with surgically treated thoracolumbar fractures operated between January 2007 and January 2018. The potential risk factors for the development of AEs as well as the development of common complications were evaluated by univariate analysis, and a multivariate logistic regression analysis was performed to identify independent risk factors predictive of the above.Results: The overall rate of AEs was 46.7%; 83 patients (41.7%) had nonsurgical AEs, whereas 24 (12.1%) had surgical adverse events. The most common AEs were urinary tract infections in 43 patients (21.6%), and hospital-acquired pneumonia in 21 patients (10.6%). On multivariate logistic regression, a Thoracolumbar Injury Classification and Severity (TLICS) score of 8–10 (odds ratio [OR], 6.39; 95% confidence interval [CI], 2.33–17.51), the presence of polytrauma (OR, 2.64; 95% CI, 1.17–5.99), and undergoing open surgery (OR, 2.31; 95% CI, 1.09–4.88) were significant risk factors for AEs. The absence of neurological deficit was associated with a lower rate of AEs (OR, 0.47; 95% CI, 0.31–0.70).Conclusions: This study suggests the presence of polytrauma, preoperative American Spinal Injury Association score, and TLICS score are predictive of AEs in patients with surgically treated thoracolumbar fractures. The results might also suggest a role for minimally invasive surgical methods in reducing AEs in these patients.

Making a Traditional Spine Surgery Clinic Telemedicine-Ready in the “New Normal” of Coronavirus Disease 2019

Liu Ka-Po Gabriel,Tan Wei Loong Barry,Yip Wei Luen James,Tan Jun-Hao,Wong Hee-Kit 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.2

Study Design: An original article describing a comprehensive methodology for making a traditional spine surgery clinic telemedicineready in terms of logistical considerations and workflow.Purpose: The aim of this study is to promote the use of telemedicine via videoconferencing to reduce human exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reduce the risk of coronavirus disease 2019 (COVID-19) transmission at outpatient clinics.Overview of Literature: The COVID-19 pandemic is the biggest healthcare crisis in the 21st century. Until a vaccine is developed or herd immunity against SARS-CoV-2 is achieved, social distancing to avoid crowding is an important strategy to reduce disease transmission and resurgence. Telemedicine has already been applied in the field of orthopedics with encouraging results.Methods: We reviewed the evidence behind telemedicine and described our clinical protocol, patient selection criteria, and workflow for telemedicine. We discussed a simple methodology to convert pre-existing traditional clinic resources into telemedicine tools, along with future challenges.Results: Our methodology was successfully and easily applied in our clinical practice, with a streamlined workflow allowing our spine surgery service to implement telemedicine as a consultation modality in line with the national recommendations of social distancing.Conclusions: Telemedicine was well incorporated into our outpatient practice using the above workflow. We believe that the use of telemedicine via videoconferencing can become part of the new normal and a safe strategy for healthcare systems as both a medical and an economic countermeasure against COVID-19.

Screw Back-Out Following “Open-Door” Cervical Laminoplasty: A Review of 165 Plates

Gabriel Liu,Jacob M. Buchowski,K. Daniel Riew 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.6

Study Design: Retrospective study. Purpose: To investigate safety profile of open door laminoplasty plates. Overview of Literature: Few reports have documented potential complications related to the use of cervical laminoplasty plates. Methods: Records and radiographs of consecutive plated laminoplasty patients of one academic surgeon were analyzed. Group1 had screw back-out, defined as change in screw position, and group 2 did not. Results: Forty-two patients (mean age, 56.9) underwent “open-door” cervical laminoplasty using 165 plates. Mean follow-up was 24 months (range, 12–49 months). Mean Nurick grade improved from 2.1 to 0.9 postoperatively. Cervical lordosis (C2–7) was 12.1° preoperatively and 10.0° postoperatively. Range-of-motion was 27.0° preoperatively and 23.4° postoperatively. Partial screw back-out was noted in 27 of 165 plates (16.4%) and in 34 of 660 screws (5.2%). Of the 34 screws, 27 (79.4%) were at either the most cranial (12/27, 44.4%) or the most caudal (15/27, 55.5%) level. Cranially, 11/12 screws (91.7%) had back-out. Caudally, 9/15 lateral mass screws (60.0%) backed-out versus 6 laminar screws (40.0%). Of the 22 patients with screw back-out, 15 (68.2%) occurred <3 months postoperative and 6 (27.3%) occurred 4–12 months postoperative. No statistical differences were found between group 1 and 2 for age, gender, preoperative and postoperative lordosis, focal sagittal alignment, range-of-motion, or Nurick grade. Despite screw backout in 22 patients, there were no plate dislodgements, laminoplasty closure, or neurological deterioration. Conclusions: Although screw back-out may occur with the use of cervical laminoplasty plates, the use of these plates without a bone block appears to be safe and reliable. As screw back-out is most common at the cranial and caudal ends of the laminoplasty, we recommend using the maximum number of screws (typically 2 for the lateral mass and 2 for the spinous process) at these levels to secure the plate to the bone.

Validation Study of Rajasekaran’s Kyphosis Classification System: Do We Clearly Understand Single- and Two-Column Deficiencies?

Ajoy Prasad Shetty,Rajesh Rajavelu,Vibhu Krishnan Viswanathan,Kota Watanabe,Harvinder Singh Chhabra,Rishi Mukesh Kanna,Jason Pui Yin Cheung,Yong Hai,Mun Keong Kwan,Gabriel Liu,Gabriel Liu,Saumajit Bas 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.4

Study Design: Multicenter validation study.Purpose: To evaluate the inter-rater reliability of Rajasekaran’s kyphosis classification through a multicenter validation study.Overview of Literature: The classification of kyphosis, developed by Rajasekaran, incorporates factors related to curve characteristics, including column deficiency, disc mobility, curve magnitude, and osteotomy requirements. Although the classification offers significant benefits in determining prognosis and management decisions, it has not been subjected to multicenter validation.Methods: A total of 30 sets of images, including plain radiographs, computed tomography scans, and magnetic resonance imaging scans, were randomly selected from our hospital patient database. All patients had undergone deformity correction surgery for kyphosis. Twelve spine surgeons from the Asia-Pacific region (six different countries) independently evaluated and classified the deformity types and proposed their surgical recommendations. This information was then compared with standard deformity classification and surgical recommendations.Results: The kappa coefficients for the classification were as follows: 0.88 for type 1A, 0.78 for type 1B, 0.50 for type 2B, 0.40 for type 3A, 0.63 for type 3B, and 0.86 for type 3C deformities. The overall kappa coefficient for the classification was 0.68. Regarding the repeatability of osteotomy recommendations, kappa values were the highest for Ponte’s (Schwab type 2) osteotomy (kappa 0.8). Kappa values for other osteotomy recommendations were 0.52 for pedicle subtraction/disc-bone osteotomy (Schwab type 3/4), 0.42 for vertebral column resection (VCR, type 5), and 0.30 for multilevel VCRs (type 6).Conclusions: Excellent accuracy was found for types 1A, 1B, and 3C deformities (ends of spectrum). There was more variation among surgeons in differentiating between one-column (types 2A and 2B) and two-column (types 3A and 3B) deficiencies, as surgeons often failed to recognize the radiological signs of posterior column failure. This failure to identify column deficiencies can potentially alter kyphosis management. There was excellent consensus among surgeons in the recommendation of type 2 osteotomy; however, some variation was observed in their choice for other osteotomies.

Crystal structure of the DNA binding domain of the transcription factor T-bet suggests simultaneous recognition of distant genome sites

Liu, Ce Feng,Brandt, Gabriel S.,Hoang, Quyen Q.,Naumova, Natalia,Lazarevic, Vanja,Hwang, Eun Sook,Dekker, Job,Glimcher, Laurie H.,Ringe, Dagmar,Petsko, Gregory A. National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.43

<P>The transcription factor T-bet (Tbox protein expressed in T cells) is one of the master regulators of both the innate and adaptive immune responses. It plays a central role in T-cell lineage commitment, where it controls the T(H)1 response, and in gene regulation in plasma B-cells and dendritic cells. T-bet is a member of the Tbox family of transcription factors; however, T-bet coordinately regulates the expression of many more genes than other Tbox proteins. A central unresolved question is how T-bet is able to simultaneously recognize distant Tbox binding sites, which may be located thousands of base pairs away. We have determined the crystal structure of the Tbox DNA binding domain (DBD) of T-bet in complex with a palindromic DNA. The structure shows a quaternary structure in which the T-bet dimer has its DNA binding regions splayed far apart, making it impossible for a single dimer to bind both sites of the DNA palindrome. In contrast to most other Tbox proteins, a single T-bet DBD dimer binds simultaneously to identical half-sites on two independent DNA. A fluorescence-based assay confirms that T-bet dimers are able to bring two independent DNA molecules into close juxtaposition. Furthermore, chromosome conformation capture assays confirm that T-bet functions in the direct formation of chromatin loops in vitro and in vivo. The data are consistent with a looping/synapsing model for transcriptional regulation by T-bet in which a single dimer of the transcription factor can recognize and coalesce distinct genetic elements, either a promoter plus a distant regulatory element, or promoters on two different genes.</P>

Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2

Moon, Cheil,Liu, Bridget Q.,Kim, So Yeun,Kim, Esther J.,Park, Yun Ju,Yoo, Joo-Yeon,Han, Hyung Soo,Bae, Yong Chul,Ronnett, Gabriele V. Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of neuroscience research Vol.87 No.5

<P>Leukemia inhibitory factor (LIF), a neuropoietic cytokine, has been implicated in the control of neuronal development. We previously reported that LIF plays a critical role in regulating the terminal differentiation of olfactory sensory neurons (OSNs). Here, we demonstrate that LIF plays a complementary role in supporting the survival of immature OSNs. Mature OSNs express LIF, which may be elaborated in a paracrine manner to influence adjacent neurons. LIF null mice display more apoptotic immature neurons than do their wild-type littermates. LIF treatment of dissociated OSNs in vitro significantly reduces the apoptosis of immature OSNs. Double immunocytochemical analysis indicates that the survival of immature OSNs is dependent on the presence of LIF. LIF activates the phosphoinositide 3-kinase (PI3K) pathways and induces the expression of the antiapoptotic molecule Bcl-2 in OSNs, whereas inhibition of the PI3K pathway blocks LIF-dependent OSN survival and Bcl-2 induction. Thus, LIF plays a central role in maintaining the size and integrity of the population of immature neurons within the olfactory epithelium; this population is critical to the rapid recovery of olfactory function after injury. LIF may play a similar role elsewhere in the CNS and thus be important for manipulation of stem cell populations for therapeutic interventions. © 2008 Wiley-Liss, Inc.</P>

Metastable Li_1+δMn₂O₄ (0 ≤ δ ≤ 1) Spinel Phases Revealed by in Operando Neutron Diffraction and First-Principles Calculations

Song, Bohang,Veith, Gabriel M.,Park, Jinseon,Yoon, Mina,Whitfield, Pamela S.,Kirkham, Melanie J.,Liu, Jue,Huq, Ashfia American Chemical Society 2019 Chemistry of materials Vol.31 No.1

<P>In this work, we examine the reaction mechanisms driven by the lithiation of Li<SUB>1+δ</SUB>Mn<SUB>2</SUB>O<SUB>4</SUB> (0 ≤ δ ≤ 1) spinels via in operando neutron powder diffraction (NPD). New reaction mechanisms are proposed involving solid-solution regions within both cubic and tetragonal spinel phases in addition to a continuous phase transition between them. In operando NPD is an ideal tool to follow the light elements such as lithium and oxygen in cathode materials which are often the key to fully understand their structural evolutions. Here, we report a novel methodology to prepare an extremely thick electrode with ∼378 mg·cm<SUP>-2</SUP> loading density suitable for the in operando NPD studies. Enabled by such thick electrode, we find that the metal oxygen M-O (M = Li and Mn) bond lengths in both end members LiMn<SUB>2</SUB>O<SUB>4</SUB> and Li<SUB>2</SUB>Mn<SUB>2</SUB>O<SUB>4</SUB> experience pronounced changes larger than dictated by the change in lattice parameters because of the locally formed Jahn-Teller distorted Mn<SUP>3+</SUP>. First-principles density functional theory calculations confirm these metastable intermediates and further propose atomistic reaction pathways for the phase transition by coupling a global structure search algorithm. These findings redefine the conventional understandings on two-phase reactions of this spinel material.</P> [FIG OMISSION]</BR>

First Top-Down Estimates of Anthropogenic NO_<i>x</i>Emissions Using High-Resolution Airborne Remote Sensing Observations

Souri, Amir H.,Choi, Yunsoo,Pan, Shuai,Curci, Gabriele,Nowlan, Caroline R.,Janz, Scott J.,Kowalewski, Matthew G.,Liu, Junjie,Herman, Jay R.,Weinheimer, Andrew J. Wiley-Blackwell Publishing, 2018 Journal of Geophysical Research: Atmospheres Vol.123 No.6

Addressing Coronavirus Disease 2019 in Spine Surgery: A Rapid National Consensus Using the Delphi Method via Teleconference

Tan Kimberly-Anne,Thadani Vishaal Nanik,Chan Daniel,Oh Jacob Yoong-Leong,Liu Gabriel Ka-Po 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.3

The magnitude and potential duration of the current coronavirus disease 2019 (COVID-19) pandemic is something that most doctors currently in practice have yet to experience. While considerable information regarding COVID-19 is being published every day, it is challenging to filter out the most relevant or appropriate information for our individual practice. The Spine Society of Singapore convened via a teleconference on April 24, 2020 to collaborate on a national level and share collective wisdom in order to tackle the ongoing crisis. In the teleconference, 13 spine surgeons from across various hospitals in Singapore constituted the panel of experts. The following topics were discussed: repurposing of surgeons, continuity of spine services, introduction of telemedicine, triaging of spinal surgeries, preoperative testing, new challenges in performing spine surgery, and preparing for the post-pandemic era. While some issues required only the sharing of best practices, the Delphi panel method was adopted to form a consensus on others. Existing spine specific triage guidelines were debated and a locally accepted set of guidelines was established. Although preoperative testing is currently not performed routinely, the panel voted in favor of its implementation because they concluded that it is vital to protect themselves, their colleagues, and their patients. Solutions to operating room specific concerns were also discussed. This article reflects the opinions and insights shared during this meeting and reviews the evidence relevant to the issues that were raised. The rapid consensus reached during the teleconference has enabled us to be concerted, and thus stronger, in our national efforts to provide the best standard of care via our spine services in these challenging times. We believe that this article will provide some guidance for addressing COVID-19 in spine surgery and encourage other national/regional societies to conduct similar discussions that would help their navigation of this pandemic.