bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions
Authors: Lytle Evan J. , Slavnic Dejan , Tong Doris , Bahoura Matthew , Govila Lisa , Gonda Roger , Houseman Clifford , Soo Teck-Mun
Published: March 2019

Study Design.

Retrospective longitudinal cohort.

Objective.

We sought to demonstrate the minimally effective bone morphogenetic protein (BMP) dose to achieve fusion in minimally invasive transforaminal lumbar interbody fusions.

Summary of Background Data.

Multiple studies have been conducted, which used a wide range of BMP doses for lumbar fusions highlighting associated risks and benefits. There is, however, a paucity in the literature in determining the minimally effective dose.

Methods.

Consecutive patients who underwent transforaminal lumbar interbody fusion from 2009 to 2014 were reviewed. Fusion was determined by a combination of computed tomography and dynamic x-ray by independent radiologists. We used backward stepwise multiple logistic regression with fusion as the dependent variable to determine whether BMP dose/level was a significant predictor for fusion. To determine the minimally effective dose of BMP/level, separate logistic regressions for different BMP dose ranges and sensitivity analyses were used. A P value ≤0.025 was considered significant.

Results.

There were 1102 interspaces among 690 patients. Average BMP dose was 1.28 mg/level. Overall fusion was 95.2% with a mean follow-up of 19 months. BMP dose/level was a significant predictor for fusion. Odds of fusion increased by 2.02 when BMP dose range was increased from (0.16–1 mg/level) to (1.0–2 mg/level), but fusion odds did not increase when BMP dose increased to more than 2 mg/level.

Conclusion.

BMP dose/level was a significant predictor for fusion. There was a significant increase in odds of fusion when BMP dose increased from 0.16 to 1 mg/level to 1.0 to 2 mg/level. No benefit from increasing the dose more than 2 mg/level was found, suggesting 1.0 mg/level to be the minimally effective BMP dose.

Level of Evidence: 3
PROMIS Correlates With Legacy Outcome Measures in Patients With Neck Pain and Improves Upon NDI When Assessing Disability in Cervical Deformity
Authors: Johnson Bradley , Stekas Nicholas , Ayres Ethan , Moses Michael J. , Jevotovsky David , Fischer Charla , Buckland Aaron J. , Errico Thomas , Protopsaltis Themistocles
Published: March 2019

Study Design.

Retrospective cohort study.

Objective.

To evaluate the ability of patient reported outcome measurement information system (PROMIS) assessments to capture disability related to cervical sagittal alignment and secondarily to compare these findings to legacy outcome measures.

Summary of Background Data.

PROMIS is a validated patient-reported outcome metric that is increasing in popularity due to its speed of administration relative to legacy metrics. The ability of PROMIS to capture disability from sagittal alignment and baseline health status in patients with neck pain has not been investigated.

Methods.

Patients presenting with a chief complaint of neck pain from December 2016 to July 2017 were included. Demographics and comorbidities were retrospectively collected. All patients prospectively completed the neck disability index (NDI), EQ-5D, visual analog scale (VAS) neck, VAS arm, PROMIS physical function, PROMIS pain intensity, and PROMIS pain interference metrics. Cervical sagittal alignment parameters were measured on standing X-rays. The correlations between outcome measures, health status indexes, psychiatric diagnoses, and sagittal alignment were analyzed.

Results.

Two hundred twenty-six patients were included. The sample was 58.4% female with a mean age of 55.1 years. In patients with neck pain, PROMIS physical function correlated strongly with the NDI (r = −0.763, P < 0.01), EQ-5D (r = 0.616, P < 0.01), VAS neck pain (−0.466, P < 0.01), and VAS arm pain (r = −0.388, P < 0.01). One hundred seventy-seven patients (69.96%) were included in the radiographic analysis. 20.3% of the radiographic cohort had cervical deformity and in this group, less cervical lordosis correlated with PROMIS pain intensity and EQ-5D but not NDI. In patients without cervical deformity, no outcome metric was found to correlate significantly with cervical alignment parameters.

Conclusion.

PROMIS domains correlated strongly with legacy outcome metrics. For the whole cohort, sagittal alignment was not correlated with outcomes. In patients with sagittal cervical deformity, worsening alignment correlated with PROMIS pain intensity and EQ-5D but not NDI.

Level of Evidence: 3
90-day Readmission in Elective Primary Lumbar Spine Surgery in the Inpatient Setting
Authors: Rubel Nicolas C. , Chung Andrew S. , Wong Michael , Lara Nina J. , Makovicka Justin L. , Arvind Varun , Chang Michael S. , Cho Samuel K.
Published: March 2019

Study Design.

Secondary analysis of a large administrative database.

Objective.

The objectives of this study are to: 1) identify the incidence and cause of 90-day readmissions following primary elective lumbar spine surgery, 2) offer insight into potential risk factors that contribute to these readmissions, and 3) quantify the cost associated with these readmissions.

Summary of Background Data.

As bundled-payment models for the reimbursement of surgical services become more popular in spine, the focus is shifting toward long-term patient outcomes in the context of 90-day episodes of care. With limited data available on national 90-day readmission statistics available, we hope to provide evidence that will aid in the development of more cost-effective perioperative care models.

Methods.

Using ICD-9 coding, we identified all patients 18 years of age and older in the 2014 Nationwide Readmissions Database (NRD) who underwent an elective, inpatient, primary lumbar spine surgery. Using multivariate logistic regression, we identified independent predictors of 90-day readmission while controlling for a multitude of confounding variables and completed a comparative cost analysis.

Results.

We identified 169,788 patients who underwent a primary lumbar spine procedure. In total 4268 (2.5%) were readmitted within 90 days. There was no difference in comorbidity burden between cohorts (readmitted vs. not readmitted) as quantified by the Elixhauser Comorbidity index. Independent predictors of increased odds of 90-day readmission were: anemia, uncomplicated diabetes and diabetes with chronic complications, surgical wound disruption and acute myocardial infarction at the time of the index admission, self-pay status, and an anterior surgical approach. Implant complications were identified as the primary related cause of readmission. These readmissions were associated with a significant cost increase.

Conclusion.

There are clearly identifiable risk factors that increase the odds of hospital readmission within 90 days of primary lumbar spine surgery. An overall 90-day readmission rate of 2.5%, while relatively low, carries significantly increased cost to both the patient and hospital.

Level of Evidence: 3
Health-related Quality of Life and Postural Changes of Spinal Alignment in Female Adolescents Associated With Back Pain in Adolescent Idiopathic Scoliosis
Authors: Makino Takahiro , Kaito Takashi , Sakai Yusuke , Takenaka Shota , Yoshikawa Hideki
Published: March 2019

Study Design.

A prospective cross-sectional study.

Objective.

To identify risk factors for chronic back pain and back pain at rest in adolescent idiopathic scoliosis (AIS) patients, particularly focusing on the psychological backgrounds of the patients and on postural changes of radiographical parameters for spinal alignment.

Summary of Background Data.

Back pain has been recognized as a relatively common condition in AIS. However, the effect of patients’ psychological backgrounds and dynamic changes of spinal alignment on back pain are unclear.

Methods.

One hundred two consecutive female AIS patients (mean age, 14.1 yrs [range, 10–18]) who first visited our outpatient clinic between July 2013 and December 2017 were included. Using SRS-22r questionnaire, the presence of chronic back pain and back pain at rest and the scores of self-image and mental health were evaluated. Using full-length standing and supine posteroanterior radiographs, parameters related to curve profiles and coronal global balance were measured, and postural changes of these parameters were calculated. From full-length standing lateral radiographs, sagittal spinal and spino-pelvic alignment parameters were also measured. Multivariate logistic regression analysis was performed to identify risk factors for back pain.

Results.

The prevalence of chronic back pain was 22.5% and that of back pain at rest was 25.5%. Poor self-image and mental health scores in SRS-22r were identified as risk factors for chronic back pain. Higher Risser grade, poor self-image score, large postural changes of apical vertebral translation at the main thoracic curve, and hyperlordosis in the lumbar spine were identified as risk factors for back pain at rest.

Conclusion.

Psychological distress and large postural changes of spinal alignment played an important role in the occurrence of back pain. Physicians should pay more attention to mental healthcare of AIS patients as well as to radiographical assessments of curve severity for better health-related quality of life.

Level of Evidence: 4
The Use of Halo Gravity Traction in the Treatment of Severe Early Onset Spinal Deformity
Authors: Iyer Sravisht , Duah Henry Ofori , Wulff Irene , Osei Tutu Henry , Mahmud Rufai , Yankey Kwadwo Poku , Akoto Harry , Boachie-Adjei Oheneba
Published: March 2019

Study Design.

Retrospective Review of Prospective cohort.

Objective.

To describe the feasibility of preoperative halo gravity traction (HGT) with subsequent growing rod/guided growth (GR/GG) placement in early onset spinal deformity (EOSD).

Summary of Background Data.

In children with severe EOSD, primary implantation of GR/GG constructs is not always possible. We describe a staged protocol with preoperative HGT followed by GR/GG implantation.

Methods.

EOSD patients treated with HGT prior to GR/GG implantation were included. HGT used traction up to 50% body weight for 4 to 29 weeks. Pulmonary function tests (PFTs) were performed before and after HGT. Coronal Cobb (CC) and Sagittal Cobb (SC) angles were measured on the Pre-HGT, Post-HGT and 6 week postop x-rays.

Results.

Thirty patients were included. Average age at GR/GG implantation was 9 years. Most cases (n = 24, 80%) were idiopathic. Most pts had kyphoscoliosis (n = 16, 53.3%). Pre-HGT CC averaged 112 ± 22° and SC averaged 106 ± 26°. CC and SC improved 29% after HGT. There was a significant improvement in body mass index following HGT. CC improved further to 70 ± 14° (36% vs. pre-HGT) and SC to 63 ± 21° (41%) with GR/GG placement. HGT-related complications occurred in nine patients (30%); eight pin site infections, one cranial abscess. Most HGT complications were managed with local pin care and oral antibiotics. Halo revision was required in two pts (6.7%). There was no change in PFTs with HGT (P > 0.05). Averagely, 14 levels were spanned during GR/GG implantation; two patients required vertebral column resection. Surgical complications occurred in nine (30%) patients. At average 16 month follow-up, seven patients (23.3%) required reoperation.

Conclusion.

Preoperative HGT can make severe EOSD curves amenable to GR/GG implantation. HGT results in ∼30% correction with improvement to ∼35–40% following GR/GG. HGT has a 30% complication rate but most are pin-site infections managed with pin-site care and oral antibiotics; 6.7% of patients require revision.

Level of Evidence: 4
Spinal Fusion in Parkinson's Disease Patients
Authors: Shah Neil V. , Beyer George A. , Solow Maximillian , Liu Shian , Tarabichi Saad , Stroud Sarah G. , Hollern Douglas A. , Bloom Lee R. , Liabaud Barthélemy , Agarwal Sanjeev , Passias Peter G. , Paulino Carl B. , Diebo Bassel G.
Published: March 2019

Study Design.

Retrospective analysis.

Objective.

To compare outcomes and complication rates between patients with and without Parkinson's disease (PD) patients undergoing surgery for adult spinal deformity (ASD).

Summary of Background Data.

There is limited literature evaluating the impact of PD on long-term outcomes after thoracolumbar fusion surgery for ASD.

Methods.

Patients admitted from 2009 to 2011 with diagnoses of ASD who underwent any thoracolumbar fusion procedure with a minimum 2-year follow-up surveillance were retrospectively reviewed using New York State's Statewide Planning and Research Cooperative System. A 1:1 propensity score-match by age, Deyo score, and number of fused vertebral levels was conducted before comparing surgical outcomes of patients with ASD with and without PD. Univariate analysis compared demographics, complications, and subsequent revision. Multivariate binary stepwise logistic regression models identified independent predictors of these outcomes (covariates: age, sex, Deyo Index score, and PD diagnosis).

Results.

A total of 576 propensity score-matched patients were identified (PD: n = 288; no-PD: n = 288), with a mean age of 69.7 years (PD) and 70.2 years (no-PD). Each cohort had comparable distributions of age, sex, race, insurance provider, Deyo score, and number of levels fused (all P > 0.05). Patients with PD incurred higher total charges across ASD surgery–related visits ($187,807 vs. $126,610, P < 0.001), yet rates of medical complications (35.8% PD vs. 34.0% no-PD, P = 0.662) and revision surgery (12.2% vs. 10.8%, P > 0.05) were comparable. Postoperative mortality rates were comparable between PD and no-PD cohorts (2.8% vs. 1.4%, P = 0.243). Logistic regression identified nine-level or higher spinal fusion as a significant predictor for an increase in total complications (odds ratio = 5.64); PD was not associated with increased odds of any adverse outcomes.

Conclusion.

Aside from higher hospital charges incurred, patients with PD experienced comparable overall complication and revision rates to a propensity score-matched patient cohort without PD from the general population undergoing thoracolumbar fusion surgery. These results can support management of concerns and postoperative expectations in this patient cohort.

Level of Evidence: 3
Quantitative Correction of Cervical Sagittal Deformity in Atlanto-Axial Dislocation
Authors: Liu Zhenlei , Duan Wanru , Wu Hao , Wang Xingwen , Qian Yu , Wang Kai , Guan Jian , Jian Fengzeng , Chen Zan
Published: March 2019

Study Design.

A mechanism-based reasoning and retrospective cohort study.

Objective.

To establish a quantitative relationship between the change of clivo-axial angle (CXA) and the change of subaxial cervical lordosis (CL) in correction surgery of atlantoaxial dislocation (AAD).

Summary of Background Data.

The evolving understanding of mechanism has dramatically improved the treatment modality of AAD. Cervical sagittal alignment is another important aspect of the surgery, in addition to reduction of odontoid process. However, a quantitative reference for correction surgery has not been established.

Methods.

Frankfort-axial angle (FXA) was introduced. Based on two assumptions, (1) sagittal alignment of the spine aims at keeping horizontal gaze and (2) deformities at craniovertebral junction make little impact on slope of T1 vertebra, we deduced that the change of CXA equaled change of CL (ΔCXA = −ΔCL). We retrospectively reviewed our case cohort to validate this finding with linear regression analysis.

Results.

Sixteen cases (eight male and eight female, mean age 40.4±12.5 yr old) were included. Liner fitting equation for ΔFXA and ΔCXA is y=1.005x (coefficient of determination, R2=0.966; significance of the estimated coefficients P<0.001, t-statistics) and that for ΔCL and ΔCXA is y=−1.023x (R2=0.976, P<0.001). These results support our deduction that ΔCXA = −ΔCL, which can be used as a guidance of quantitative correction of sagittal deformity in AAD.

Conclusion.

Correction of CXA will influence the subaxial cervical lordosis (ΔCXA = −ΔCL) of AAD patients. This equation can serve as a quantitative reference for preoperative planning and intraoperative refining of the correction of cervical sagittal deformity in AAD.

Level of Evidence: 4
Origins, Courses, and Distributions of the Lumbar Arterial Branches in Relation to the Spinal Nerves
Authors: Tatara Yasunori , Nasu Hisayo , Tsutsumi Masahiro , Akita Keiichi
Published: March 2019

Study Design.

Observational, anatomical, cadaveric study.

Objective.

To investigate the origins, courses, and distributions of the lumbar arterial branches in relation to the spinal nerves using Japanese cadavers.

Summary of Background Data.

Lumbar arterial branches to the spinal nerves can be damaged during posterior lumbar column osteotomy, leading to neurological complications. Spinal cord ischemia via arterial ligation has been reported to be a major cause of neurological complications in anterior thoracolumbar surgery. Although neurological deficits have been considered the most common complications in lumbar pedicle subtraction osteotomy, there is little information on the possible neurological deficits due to spinal nerve ischemia caused by damage to the lumbar arterial branches.

Methods.

In total, 111 lumbar arteries (1 lumbar artery was damaged) from 14 embalmed cadavers (28 sides, L1–L4) were investigated. We examined the branching patterns and measured their diameter and length. Branches to the spinal nerves were classified as follows: radicular branch (Rb), spinal nerve branch (SNb), and plexus branch (Pxb).

Results.

The Rb was identified most frequently at L1 (21.4%) and included the main branch to supply the spinal cord. The SNb diverged from the dorsal branch (59.4%) and was mainly detected at L2 (85.7%) and L3 (85.2%). The Pxb originated from the lumbar artery (56.1%) and was found most frequently at L4 (75%). The Pxb had a larger diameter and a longer length at L3 and L4 than the SNb. Both the L3 and L4 Pxbs were the main blood suppliers to the femoral nerve.

Conclusion.

The L3 and L4 Pxbs mainly supplied the femoral nerve. The Pxb is likely to exist in the medial side of the spinal nerve in the extraforaminal region. Thus, the Pxb should be recognized as a very important arterial branch during operation procedures.

Level of Evidence: 5
Comparative Clinical Effectiveness of Tubular Microdiscectomy and Conventional Microdiscectomy for Lumbar Disc Herniation
Authors: Wang Yinqing , Liang Zeyan , Wu Jianfeng , Tu Songjie , Chen Chunmei
Published: March 2019

Study Design.

This study is a systematic literature review and meta-analysis.

Objective.

To evaluate the efficacy of tubular microdiscectomy (TMD) compared with conventional microdiscectomy (CMD) for lumbar disc herniation (LDH).

Summary of Background Data.

TMD has developed rapidly due to reduced tissue trauma by minimization of the required access to spine and disc herniation; however, CMD remains the standard of care for this patient group. To date, it remains debatable whether TMD is superior to CMD for LDH.

Methods.

We performed a comprehensive database search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trails for prospective randomized controlled trials (RCTs), through using Medical Subject Headings (MeSH) terms “microdiscectomy,” “tubular microdiscectomy,” “minimally invasive surgery,” and “spinal disease.” The retrieved results were last updated on March 15, 2018. Two independent investigators selected qualified studies, extracted indispensable data, assessed risk of bias of original papers. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to grade quality of evidence. If I
2 >50, the heterogeneity is considerable.

Results.

Four RCT studies (total n = 605), involving 610 individuals with a follow-up period of no less than 12 months, were selected for further review. We assessed these studies as low overall risk of bias. There was low-quality evidence that TMD was superior to CMD considering postoperative Oswestry Disability Index scores (SMD, –3.43, 95% CI, –4.64 to –2.21, P < 0.00001). Compared with CMD, the TMD group exhibited significantly worse Short Form-36 physical function scores (SMD, –4.83, 95% CI, –8.94 to –0.72, P = 0.02). There were no significant differences in the visual analogue scale (P = 0.30), operative time (P = 0.68), dural tear (P = 0.52), and reoperation (P = 0.98).

Conclusion.

The benefits 1 year after TMD were similar to that of CMD. There was no significant difference in the incidence of reoperation and dural tear.

Level of Evidence: 1
Pain Intensity and Fear Avoidance Explain Disability Related to Chronic Low Back Pain in a Saudi Arabian Population
Authors: Alamam Dalyah M. , Moloney Niamh , Leaver Andrew , Alsobayel Hana I. , Mackey Martin G.
Published: March 2019

Study Design.

A cross-sectional study.

Objective.

The aim of this study was to describe multi-dimensional profiles for people with chronic low back pain (CLBP) and to examine the associations between CLBP-related disability and individual, psychosocial and physical factors in a Saudi population.

Summary of Background Data.

CLBP-related disability is a multidimensional phenomenon. There is growing interest in exploring factors associated with CLBP-related disability in Saudi Arabia but research is limited in comparison to other countries.

Methods.

Participants completed questionnaires covering demographics, pain intensity, back beliefs, fear avoidance, psychological distress, and physical activity. Oswestry Disability Index (ODI) was used to measure disability. Participants also performed a standardized sequence of physical performance tests and a Pain Behavior Scale was used to evaluate pain behaviors during performance of these tests. The relationships between disability and all variables were explored using univariate and multivariate regression analyses.

Results.

One hundred and fifteen participants were included, 63% of whom were female. Participants demonstrated moderate disability (mean [SD]: 26.6 [13.5]). The mean (SD) back beliefs score was 28.6 (7.3). Mean depression, anxiety, and stress (DASS 21) scores indicated mild distress; however, 26% to 39% scored in the moderate to severe range for at least one subscale. In univariate analyses, pain intensity and fear avoidance beliefs (physical activity and work) were moderately associated with disability (r = 0.56, 0.49, 0.52, respectively, P < 0.001), with all other factors demonstrating weak association. Multivariate regression revealed that pain intensity, fear avoidance beliefs, psychological distress, and participants’ age were all found to be associated with disability, accounting for 52.9% (adjusted R

2
 = 0.529) of variability.

Conclusion.

This study provides a unique insight into the clinical profile of people with CLBP in a Saudi Arabian population. Pain and psychosocial factors were significantly associated with disability. This study supports the contention that CLBP-related disability is a multifactorial biopsychosocial condition across different cultures.

Level of Evidence: 3
A Novel Technique for Total En bloc Spondylectomy of the Fifth Lumbar Tumor Through Posterior-Only Approach
Authors: Yang Xinghai , Yang Jian , Jia Qi , Zhong Nanzhe , Jiao Jian , Hu Jinbo , Peng Dongyu , Liu Weibo , Wan Wei , Xiao Jianru
Published: March 2019

Study Design.

A retrospective study.

Objective.

To describe a new surgical technique for total en bloc spondylectomy (TES) of the fifth lumbar (L5) tumor and evaluate the efficacy and safety of this new technique.

Summary of Background Data.

TES has been considered an optimal treatment for tumor, including certain spinal tumors, but it requires a combined posterior–anterior approach, which is often complicated by a long operation time, considerable blood loss and severe trauma.

Methods.

Seven patients with primary or solitary metastatic tumors of L5 were treated with this new technique in our center between March 2014 and November 2017. The critical points were fabrication of the iliac graft, dissection, resection, and reconstruction. Other parameters including surgical time, blood loss, complications, pre- and postoperative neurological function, tumor control, and overall survival (OS) were presented and analyzed.

Results.

All the included patients received one stage TES. The mean surgical time was 365.7 minutes with an average blood loss of 2514.3 mL. No serious perioperative complication was observed or reported during the mean follow-up period of 27.4 months. Wound disruption occurred in one patient and numbness of the left lower limb in another, but both recovered rapidly after appropriate management. Adventitial avulsion of the abdominal aorta occurred during dissection in one patient. Two patients died during the follow-up period due to advanced malignancy. One patient was alive but developed a newly diagnosed thoracolumbar tumor in 40 months. The other four patients recovered well without evidence of disease. All patients were able to walk independently 3 to 4 weeks after operation, with satisfied fusion of the iliac grafts in a mean period of 6.7 months after operation. No evidence of internal fixation failure occurred.

Conclusion.

This new technique offers satisfactory surgical exposure, total en bloc spondylectomy, reliable reconstruction, and good tumor control for certain L5 tumors through the posterior-only approach.

Level of Evidence: 4
Gadolinium Enhancement Is Not Associated With Disc Inflammation in Patients With Sciatica
Authors: Djuric Niek , Yang Xiaoyu , Barzouhi Abdelilah el , Ostelo Raymond W.J.G. , Duinen Sjoerd G. van , Nijeholt Geert J. Lycklama à , van der Kallen Bas F.W. , Peul Wilco C. , Vleggeert-Lankamp Carmen L.A.
Published: March 2019

Study Design.

Retrospective observational histological study.

Objective.

To evaluate the reliability of gadolinium enhancement as a marker for inflammation by associating gadolinium enhancement findings with the degree of inflammation as measured by macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica.

Summary of Background Data.

Disc inflammation often occurs in sciatica patients, a noninvasive tool that is used to assess disc inflammation is Gadolinium enhanced MR imaging.

Methods.

Disc tissue was retrieved from patients in the Sciatica trial (N = 119), a multicenter randomized controlled trial in patients with sciatica. Disc tissue was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0–10 macrophages/cm2), moderate (10–100 macrophages/cm2), and considerable (>100 macrophages/cm2) inflammation. Of the 119 MRIs, 96 were additionally performed with contrast-enhanced gadolinium.

Results.

Seventy-four patients showed gadolinium enhancement of the disc herniation and 26 of the nerve root. Degree of inflammation by macrophages was not associated with gadolinium enhancement of nerve roots or herniated discs. These results did not change if the patient groups with and without Modic type 2 changes were evaluated separately. Furthermore, no associations were observed between gadolinium enhancement and presence of Modic type 2 changes.

Conclusion.

This study found gadolinium enhanced MRI findings to be unreliable as an indicator for inflammation of disc herniation or nerve root in patients with sciatica.

Level of Evidence: 2
AMP-Activated Protein Kinase Activation in Dorsal Root Ganglion Suppresses mTOR/p70S6K Signaling and Alleviates Painful Radiculopathies in Lumbar Disc Herniation Rat Model
Authors: Liu Yuantong , Li Jianmin , Li Hao , Shang Yue , Guo Yan , Li Zhenzhong , Liu Zhen
Published: March 2019

Study Design.

Animal experiment: a rat model of lumbar disc herniation (LDH) induced painful radiculopathies.

Objective.

To investigate the role and mechanism of AMP-activated protein kinase (AMPK) in dorsal root ganglia (DRG) neurons in LDH-induced painful radiculopathies.

Summary of Background Data.

Overactivation of multiple pain signals in DRG neurons triggered by LDH is crucial to the development of radicular pain. AMPK is recognized as a cellular energy sensor, as well as a pain sensation modulator, but its function in LDH-induced pain hypersensitivity remains largely unknown.

Methods.

The LDH rat model was established by autologous nucleus pulposus transplantation into the right lumbar 5 (L5) nerve root. At different time points after AMPK agonist metformin (250 mg/kg/d) or mammalian target of rapamycin (mTOR) inhibitor rapamycin (5 mg/kg) intraperitoneal administration, thermal and mechanical sensitivity were evaluated by measuring paw withdrawal latency (PWL) and 50% paw withdrawal thresholds (PWT). The levels of AMPK, mTOR, and p70S6K phosphorylation were determined by Western blot. We also investigated the proportion of p-AMPK positive neurons in the right L5 DRG neurons using immunofluorescence.

Results.

LDH evoked persistent thermal hyperalgesia and mechanical allodynia on the ipsilateral paw, as indicated by the decreased PWL and 50% PWT. These pain hypersensitive behaviors were accompanied with significant inhibition of AMPK and activation of mTOR in the associated DRG neurons. Pharmacological activation of AMPK in the DRG neurons not only suppressed mTOR/p70S6K signaling, but also alleviated LDH-induced pain hypersensitive behaviors.

Conclusion.

We provide a molecular mechanism for the activation of pain signals based on AMPK-mTOR axis, as well as an intervention strategy by targeting AMPK-mTOR axis in LDH-induced painful radiculopathies.

Level of Evidence: N/A
Ischemic Optic Neuropathy Following Spine Surgery
Authors: Goyal Anshit , Elminawy Mohamed , Alvi Mohammed Ali , Long Timothy R. , Chen John J. , Bradley Elizabeth , Freedman Brett A. , Bydon Mohamad
Published: March 2019

Study Design.

Case–control analysis and systematic literature review.

Objective.

To illustrate the prognosis and perioperative risk factors associated with this condition.

Summary of Background Data.

Ischemic optic neuropathy (ION) is the most common pathological diagnosis underlying postoperative vision loss. It comes in two primary forms—anterior (AION)—affecting the optic disc or posterior (PION) affecting the optic nerve proximal to the disc. Spine surgery remains one of the largest sources of acute perioperative visual loss.

Methods.

We performed a 1:4 case–control analysis (by age and year of surgery) for patients with ION and those who didn’t develop ION following spine surgery at our institution. A systematic literature search of Medline, Embase, Scopus from inception to September 2017 as also performed.

Results.

We identified 12 cases from our institution. Comparison to 48 matched controls revealed fusion, higher number of operative levels, blood loss, and change in hemoglobin, hematocrit to be significantly associated with ION. Majority were diagnosed with PION (83%, 10/12) and had bilateral presentation (75%, 9/12). Only 30% patients (3/10) demonstrated improvement in visual acuity while the rest remained either unchanged (40%, 4/10) or worsened (20%, 2/10) at last follow-up. Literature review identified 182 cases from 42 studies. Posterior ischemic optic neuropathy (PION) was found in 58.7% (114/194) of cases, anterior ischemic optic neuropathy (AION) in 17% (33/19) and unspecified ION in 24% (47/194). PION was associated with higher odds of severe visual deficit at immediate presentation (odds ratio [OR]: 6.45, confidence interval [CI]: 1.04–54.3, P = 0.04) and last follow-up.

Conclusion.

PION is the most common cause of vision loss following spine surgery and causes more severe visual deficits compared with AION. Prone spine surgery especially multi-level fusions with longer operative time, higher blood loss, and intraoperative hypotension are most associated with the development of this devastating complication.

Level of Evidence: 3
ERRFI1 Inhibits Proliferation and Inflammation of Nucleus Pulposus and Is Negatively Regulated by miR-2355-5p in Intervertebral Disc Degeneration
Authors: Guo Yusong , Tian Lijun , Liu Xing , He Yinxi , Chang Songtao , Shen Yong
Published: March 2019

Study Design.

In vivo and in vitro studies of the role of miR-2355-5p and its possible targets in intervertebral disc degeneration (IVDD).

Objective.

To elucidate the regulatory role of miR-2355-5p in IVDD and the underlying mechanisms.

Summary of Background Data.

IVDD, which is caused by multiple factors, is the main cause of lower back pain with or without extremity pain. However, the underlying cellular mechanisms of IVDD pathogenesis are not well elucidated. Cell hyper-proliferation, inflammation, and epidermal growth factor receptor activation have been implicated in IVDD. Up-regulated miR-2355-5p level was identified to associate with IVDD. ERRFI1 (the product of mitogen-inducible gene 6 [MIG6]) was known to inhibit epidermal growth factor receptor activation.

Methods.

We monitored the expression of miR-2355-5p and ERRFI1 in IVDD tissues and lipopolysaccharides (LPS)-treated nucleus pulposus (NP) cells. We explored the effects of ERFFI1 on NP cells proliferation and LPS-induced pro-inflammatory cytokines production. We searched the targets of miR-2355-5p and explored the effects of miR-2355-5p on NP cells proliferation and cytokines production.

Results.

We identified the up-regulation of miR-2355-5p and down-regulation of ERFFI1 in IVDD samples and LPS-treated NP cells. ERFFI1 inhibited NP cells proliferation and LPS-induced pro-inflammatory cytokine production. MiR-2355-5p targeted ERFFI1 and negatively regulated ERFFI1 expression. MiR-2355-5p regulated IVDD by targeting ERFFI1.

Conclusion.

MiR-2355-5p negatively regulated ERFFI1 and prevented the effects of ERRFI1 on inhibiting NP cells proliferation and inflammation.

Level of Evidence: N/A
Sagittal Alignment Outcomes in Lordotic Cervical Spine
Authors: Liang Guoyan , Liang Changxiang , Zheng Xiaoqing , Xiao Dan , Zeng Shixing , Yin Dong , Zhan Shiqiang , Ye Juntong , Liu Xiao , Chang Yunbing
Published: March 2019

Study Design.

A prospective cohort study.

Objective.

To compare the radiological outcomes between three-level anterior cervical discectomy and fusion (ACDF) and plate-only open-door laminoplasty (LAMP) in patients with lordotic cervical spine.

Summary of Background Data.

Both three-level ACDF and LAMP are important surgical methods for multilevel cervical spondylotic myelopathy, but the cervical sagittal alignment outcomes and the lordosis preserving abilities between the two specific approaches have not been carefully compared.

Methods.

Sixty patients, all of whom had lordotic cervical spines and underwent three-level ACDF (n = 22) or LAMP (n = 38) for the treatment of multilevel cervical spondylotic myelopathy, were prospectively studied. Upright neutral cervical lateral radiographs were assessed preoperatively, at 3 days after surgery, and at the last follow-up (1.5 years). The primary radiological outcomes are C2–7 Cobb angle, and the secondary outcomes include C2–7 sagittal vertical axis , disc height, Harrison angle, and Ishihara index. The relationship between preoperative parameters and follow-up outcomes were assessed.

Results.

Preoperative cervical sagittal alignment parameters were similar between the two groups. Patients in the ACDF group obtained larger C2–7 Cobb angles than those the LAMP group early after surgery. However, the lordosis in the ACDF group decreased significantly during follow-up, leading to similar outcomes between the two groups. The lordosis-preserving ability of ACDF is significantly poorer than that of LAMP. Secondary radiological parameters also showed similar trends. In both groups, the preoperated Ishihara index was significantly related to follow-up C2–7 Cobb angles. For patients with Ishihara index less than 20, ACDF is more likely to produce a larger C2–7 Cobb angled at the time of follow-up.

Conclusion.

In patients with lordotic cervical spine, the sagittal alignment outcomes of the two approaches were similar, and the lordosis-preserving ability was poorer in ACDF. Further research should focus on the factors related to the lordosis-preserving ability of multilevel ACDF.

Level of Evidence: 3
Sagittal Alignment With Downward Slope of the Lower Lumbar Motion Segment Influences Its Modes of Failure in Direct Compression
Authors: Sapiee Nurul Haiza , Thambyah Ashvin , Robertson Peter A. , Broom Neil D.
Published: March 2019

Study Design.

Microstructural investigation of compression-induced herniation of ovine lumbar discs with and without added component of anterior-inferior slope.

Objective.

Does increased shear arising from a simulated component of motion segment slope imitating sacral slope weaken the lateral annulus and increase risk of overt herniation at this same region.

Summary of Background Data.

An increase in sacral slope secondary to lordosis and pelvic incidence increases shear stresses at the lumbosacral junction and has been associated with an increase in spondylolisthetic disorders and back injury. The small component of forward shear induced when a segment is compressed in flexion is suggested to cause differential recruitment of the lateral annular fibers leading to its early disruption followed by intra-annular nuclear tracking to the posterolateral/posterior regions. However, the influence of even greater forward shear arising from the added component of slope seen where pelvic incidence and lumbar lordosis are increased in the lower lumbar spine is less understood.

Methods.

Ovine motion segments were compressed at 40 mm/min up to failure; 9 with a horizontal disc alignment and 26 with a segment slope of 15° and then analyzed structurally.

Results.

All the horizontal discs failed (11.8 ± 2.4 kN) via vertebral fracture without any evidence of soft tissue failure even in the lateral aspects of the discs. The increased forward shear resulting from the slope decreased the failure load (6.4 ± 1.6 kN). The sloping discs mostly suffered mid-span, noncontinuous disruption of the lateral annulus with some extruding nuclear material directly from these same lateral regions.

Conclusion.

The increased level of forward shear generated in moderately sloping lumbar segments when compressed was abnormally damaging to the lateral regions of the disc annulus. This is consistent with the view that shear differentially loads the oblique-counter oblique fiber sets in the lateral annulus, increasing its vulnerability to early disruption and overt herniation.

Level of Evidence: N/A
Psychometric Properties of the Hindi Version of the Fear-Avoidance Beliefs Questionnaire in Patients With Chronic Non-Specific Low Back Pain
Authors: Panhale Vrushali P. , Gurav Reshma S. , Shah Pooja , Nayak Neelam
Published: March 2019

Study Design.

Prospective cohort study.

Objective.

To translate, adapt, and establish psychometric properties of the Fear-Avoidance Beliefs Questionnaire (FABQ) for Hindi-speaking patients with chronic non-specific low back pain.

Summary of Background Data.

The FABQ is a patient-reported measure to assess beliefs regarding how physical activity and work are influenced based on fear related to low back pain.

Methods.

Standardized translation guidelines were implemented to confirm Hindi-version of the FABQ (FABQ-H). A cross-sectional study design was utilized. Construct validity analysis included factor analysis of the FABQ and use of Pearson correlation coefficients to report convergent and divergent validity. Reliability assessment included calculation of intraclass correlation coefficient (ICC) and Cronbach α for internal consistency. Outcome measures consisted of Numeric Rating Scale (NRS), Roland Morris Disability Questionnaire (RMDQ) Hindi, and Tampa Scale of Kinesiophobia (TSK).

Results.

In total, 100 patients with chronic non-specific low back pain were recruited, with a mean age of 36.89 (±7.78). Factor analysis revealed a three-factor structure of the FABQ, which consisted of subscales FABQ Physical activity, FABQ Work, and FABQ Work prognosis. Convergent validity analysis demonstrated a moderate correlation between FABQ-H and TSK (r = 0.413). Divergent validity analysis displayed a moderate correlation between FABQ-H and NRS (r = 0.362) and RMDQ Hindi (r = 0.399). ICC value for the FABQ-H was observed as 0.938 indicating high significance for test–retest reliability. Cronbach α for the FABQ-H was recorded as 0.806 demonstrating high internal consistency.

Conclusion.

A successful translation and adaptation of the Hindi version of FABQ is reported in this study. The three-factored FABQ-H exhibited satisfactory construct validity, test–retest reliability, and internal consistency. Based on findings of this study, the FABQ-H can be implemented in Hindi-speaking patients with chronic non-specific low back pain (LBP).

Level of Evidence: 3
Immunoglobulin G and Subclasses as Potential Biomarkers in Metastatic Melanoma Patients Starting Checkpoint Inhibitor Treatment
Authors: Diem Stefan , Fässler Mirjam , Bomze David , Ali Omar Hasan , Berner Fiamma , Niederer Rebekka , Hillmann Dorothea , Mangana Joanna , Levesque Mitchell P. , Dummer Reinhard , Risch Lorenz , Recher Mike , Risch Martin , Flatz Lukas
Published: March 2019

Checkpoint inhibitors have improved survival of metastatic melanoma. However, reliable biomarkers to predict response are still needed. Immunoglobulin G (IgG) antibody subclasses reflect immunocompetence in individuals and are known to be involved in essential functions in our immune system. This prospective study evaluated the association between serum IgG with its subclasses IgG1, IgG2, IgG3, and IgG4 and antitumor response according to RECIST 1.1. Serum samples from 49 patients were prospectively collected before the start of treatment with a checkpoint inhibitor. We observed a statistically significant association of baseline IgG2 with response to therapy (P=0.011). After defining optimal cutpoints, we found significant associations between total IgG (>9.66 g/L, P=0.038), IgG1 (>6.22 g/L, P=0.025), IgG2 (>2.42 g/L, P=0.019), and IgG3 (>0.21 g/L, P=0.034) with progression-free survival. Prolonged overall survival was associated with elevated IgG2 (>2.42 g/L, P=0.043). Together, these findings define total IgG and subclasses as predictors of clinical successful checkpoint inhibition in metastatic melanoma patients.
Checkpoint inhibitor treatment induces an increase in HbA1c in nondiabetic patients
Authors: Gauci Marie-Léa , Boudou Philippe , Squara Pierre-Alexandre , Delyon Julie , Allayous Clara , Mourah Samia , Resche-Rigon Matthieu , Lebbé Céleste , Baroudjian Barouyr , Gautier Jean-François
Published: March 2019

Immunotherapy greatly improves clinical outcomes in treated patients with cancer. However, the long-lasting immune response and long duration of therapy could induce long-term adverse effects owing to the chronic inflammation induced. Type 2 diabetes is now recognized as an inflammatory disease. In addition, immunotherapy is concerned with increase in the production of tumor necrosis factor-α, interleukin-2, and interferon-γ, which are involved in the inflammatory process. Based on these observations, we hypothesized that anti-programmed cell death-1 (anti-PD-1) and/or anticytotoxic T-lymphocyte-associated protein-4 therapy could contribute to type 2 diabetes genesis in treated patients. Therefore, to evaluate this hypothesis, we studied HbA1c levels during follow-up in patients treated with anti-PD-1 and/or anticytotoxic T-lymphocyte-associated protein-4 therapy. A prospective and observational study was performed in an oncodermatology department (Saint-Louis Hospital, Paris, France) from March 2015 to February 2017. Sixty-two patients meeting the inclusion criteria were enrolled. Forty-three patients had paired HbA1c measurements during their follow-up period and were analyzed. The median follow-up was 3 months. We noted an increase in HbA1c levels from 5.3% [interquartile range (IQR): 5.1–5.5; range: 4.5–6.2) to 5.45% (IQR: 5.2–5.7; range: 4.7–6.2; P=0.037). This observation was confirmed in the subgroup of patients who did not receive concomitant glucocorticoids; their median HbA1c levels increased from 5.3% (IQR: 5.1–5.5; range: 4.7–6.2) to 5.5% (IQR: 5.2–5.7; range: 4.7–6.3; P=0.025). Variables such as age, BMI, and sex were not associated with the HbA1c level increase, but a tendency toward rising HbA1c levels was observed in treatments longer than 12 months. This study demonstrates that treatment with anti-PD-1 antibodies may impair glucose metabolism, as measured by increasing HbA1c levels.
The Efficacy of Combining Fractional Carbon Dioxide Laser With Verapamil Hydrochloride or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Clinical and Immunohistochemical Study
Authors: Sabry Hanan H. , Abdel Rahman Sherine H. , Hussein Mohamed S. , Sanad Rana R. , Abd El Azez Taghreed A.
Published: March 2019

BACKGROUND

Ablative fractional laser-assisted therapy is increasingly used to facilitate drug delivery and intensify clinical efficacy of topically applied drugs.

OBJECTIVE

To evaluate the effectiveness of combined ablative fractional CO2 laser and topically applied 5-fluorouracil (5-FU) or verapamil hydrochloride in the treatment of hypertrophic scars (HTSs) and keloids and to examine their possible effects on TGF-β1 expression.

PATIENTS AND METHODS

Thirty patients with HTSs and keloids were randomly treated with combined CO2 laser followed by topical verapamil or 5-FU application or CO2 laser monotherapy. All patients received 4 treatments at 1-month intervals. Subjective and objective assessment was obtained using the Vancouver Scar Scale (VSS). Histological changes and immunohistochemical staining for TGF-β1 were performed.

RESULTS

Compared with baseline, there was a significant reduction in the VSS 1 month after the last treatment session in all groups (p < .05). Laser-assisted 5-FU delivery tended to show a higher extent of improvement in scar characteristics than laser-assisted verapamil hydrochloride delivery, without significance. No significant side effects were reported in all patient groups. TGF-β1 expression was significantly decreased after laser sessions.

CONCLUSION

Combined fractional CO2 laser and topical 5-FU or verapamil hydrochloride offer a safe therapy for HTSs and keloids.