bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparisons of Lesion Volumes and Shapes
Produced by a Radiofrequency System with a
Cooled, a Protruding, or a Monopolar Probe
Authors: Cedeño David L.
Published: February 2021

Background: Radiofrequency (RF) ablation for denervation has been utilized for decades in chronic pain
management. This relies on the proper targeting of the affected nerve which may be obtained by creating
an ablation lesion with a shape and volume that optimizes targeting. Various systems designed to improve
lesion size are available. These include cooling the active tip (cooled-RF) and protruding the RF electrode
outside the active tip (PERF).
Objectives: This study compares lesion volumes of 3 commercially available RF systems: cooled-RF, “V”
shaped active cannula and protruding electrode (18 g and 20 g), and monopolar RF (MRF; 16 g, 18 g,
and 20 g).
Study Design: Ex vivo study using clinically relevant conditions.
Setting: Biophysical laboratory in an academic institution.
Methods: RF ablation lesions were generated in additive-free chicken breast specimens (n = 10) with the
RF probes fully inserted in them. For cooled RF, a 17 g probe (4 mm active tip) was used. RF was applied for
150 seconds at 60°C. PERF was applied using 18 g or 20 g introducers (10 mm active tip) for either 90 or
150 seconds at 80°C. For MRF ablation, introducers diameter were 16 g, 18 g, or 20 g (10 mm active tip),
while RF was applied for 90 seconds at 80°C. Tissues were dissected through the midpoint of the lesion,
and measurements of the longitudinal, transversal, and depth lengths were taken and used to calculate
the lesion volume. Measurements from the distal edge in the transverse and longitudinal directions were
also recorded. One-way ANOVA was used to determine statistical significance between volume means (P
< 0.05).
Results: Mean lesion volume with cooled RF (595 mm3
) is significantly larger than any other mean
volume measured. The second largest volume is produced with MRF using a 16 g introducer (360 mm3
),
which is significantly larger than those obtained with 18 g or 20 g. This is also significantly larger than the
one obtained with PERF using an 18 g introducer. Mean lesion volume produced with PERF (80°C for 90
seconds) and an 18 g diameter tip (215 mm3
) is significantly larger than the respective one produced with
MRF (169 mm3
). Increasing lesioning time to 150 seconds significantly increases the volume (283 mm3
).
Using a 20 g tip produces the smallest lesions at 80°C for 90 seconds with either PERF or MRF, although
a lesioning time of 150 seconds makes it significantly larger (207 mm3
).
Limitations: The study is ex vivo and therefore does not account for the dynamic effects of the anatomy
and physiology of a living organism.
Conclusions: The results indicate that the lesion produced with a cooled-RF system (17 g, 4 mm tip)
is significantly larger than that produced with either of the other systems trialed (18 g or 20 g, 10 mm
active tip protruding electrode or 16 g, 18 g, or 20 g monopolar electrode). Interestingly, a 16 g, 10 mm
active tip monopolar electrode produced a larger lesion than the one produced with the 18 g protruding
electrode.
Efficacy of Magnesium Sulfate Added to Local
Anesthetic in a Transversus Abdominis Plane
Block for Analgesia Following Total Abdominal
Hysterectomy: A Randomized Trial
Authors: Abd El-Rahman Ahmad M.
Published: February 2021

Background: Major abdominal surgeries are associated with severe pain, which can affect
respiratory and cardiac functions if insufficiently treated; this increases postoperative morbidity.
Objective: We aim at evaluating the efficacy of magnesium sulfate as an adjuvant to local anesthetic
in an ultrasound-guided transversus abdominis plane (TAP) block for postoperative analgesia in total
abdominal hysterectomy.
Study Design: A prospective, randomized, double-blinded clinical trial.
Setting: An academic medical center.
Methods: This study is registered at https://clinicaltrials.gov (no.: NCT02930707). This randomized,
double-blinded clinical trial included 60 women undergoing total abdominal hysterectomy that were
divided into 2 groups (30 patients per group). Group I received a TAP block with 20 mL per side of
0.25% bupivacaine plus 2 mL magnesium sulphate 10% (200 mg). Group II received a TAP block
with 20 mL per side of 0.25% bupivacaine. Visual analog scale (VAS) scores, the time of the first
analgesic request, total morphine consumption, and any side effects were assessed and recorded.
Results: The mean postoperative VAS score was significantly reduced in group I compared to
group II in all of the time-points except after 10 hours. The mean time of the first request for rescue
analgesia was significantly prolonged in group I (15.67 hrs.) compared to group II (7.33 hrs.) (P <
0.001), and the mean total morphine consumption, over the first 24 hours postoperatively, was
significantly lower in group I (7.63 ± 2.93 mg) than in group II (16.20 ± 3.24 mg) (P < 0.001). No
significant difference in side effects was observed.
Limitations: Sample size.
Conclusion: The addition of 200 mg of magnesium sulfate to bupivacaine in an ultrasound-guided
TAP block significantly reduced postoperative opioid requirements, prolonged the duration of
analgesia, and reduced the VAS score in patients who underwent abdominal hysterectomy, without
significant side effects.
Key words: Magnesium sulfate, TAP block, postoperative pain, total abdominal hysterectomy
Exercise- and Stress-Induced Hypoalgesia in
Musicians with and without Shoulder Pain: A
Randomized Controlled Crossover Study
Authors: Roussel Dr. Nathalie
Published: February 2021

Background: Professional and pre-professional musicians are characterized by physical and
psychological demands inherent to their musical activity, and therefore at risk for developing
performance related musculoskeletal pain. Physical and psychological demands are known to
influence human pain modulation.
Objectives: In this study we compared the influence of a physically and emotionally stressful
task on pain thresholds in musicians with and without shoulder pain.
Study Design: A single-blinded randomized and controlled crossover study design was
used to compare the effects of a physical versus emotional testing procedure on pressure pain
thresholds (PPTs) in musicians with and without shoulder pain.
Setting: All data were obtained in the field (e.g., at the physiotherapy accommodation in the
Royal Conservatory).
Methods: During the physical testing procedure, the subjects performed an isometric exercise
of the glenohumeral external rotators. The emotional task comprised watching “unpleasant”
images selected from the International Affective Picture System. The outcome was the
assessment of change in PPTs before and after the physical and emotional task.
Results: Our results indicate similar effects of both protocols in either group, i.e., musicians
with and without shoulder pain (P > 0.05). All musicians showed elevated PPTs at local and
remote areas after isometric exercise (P < 0.05). The emotional stress task increased PPTs at
remote areas only (P < 0.05).
Limitations: Despite the small sample size of musicians without shoulder pain, a power
of 78.5% was achieved to detect the necessary effect size of Cohen’s d = 1. Furthermore,
comparing these results with those of non-musicians (both healthy subjects and patients with
shoulder pain) might reveal information regarding the specific adaptations. Finally a high
variability was observed in shoulder disability (i.e., SDQ-scores) as typically seen in a population
with shoulder pain.
Conclusions: In musicians with and without regional shoulder pain, no significant differences
were found with respect to pain modulation during a physically and an emotionally stressful task.
Both interventions adequately activated central and widespread pain inhibitory mechanisms in
both groups.
Key words: Pressure pain threshold, PPT, exercise induced hypoalgesia, exercise induced
analgesia, stress induced hypoalgesia, shoulder pain, musicians, regional pain:
A Seamless Navigation to ICD-10-CM for
Interventional Pain Physicians: Is a Rude
Awakening Avoidable?
Authors: Manchikanti Laxmaiah
Published: February 2021

Since October 1, 2015, the International Classification of Diseases, 10th Revision, Clinical
Modification (ICD-10-CM) was integrated into U.S. medical practices. This monumental
transition seemingly occurred rather unceremoniously, despite significant opposition and
reservations having been expressed by the provider community. In prior publications, we have
described various survival strategies for interventional pain physicians.
The regulators and beneficiaries of system – CMS, consultants, and health information
technology industry are congratulating themselves for a job well done. Nonetheless, this
transition comes at an immeasurable financial and psychological drain on providers. However, a
rude awakening may be making its way with expiration of initial concessions from government
and private payers.
This manuscript provides a template for interventional pain management professionals with
multiple steps for seamless navigation, including descriptions of the most commonly used
codes, navigation through ICD-10-CM manual, steps for correct coding, and finally, detailed
coding descriptions for various interventional techniques.
Key words: ICD-9-CM (International Classification of Diseases, Ninth revision, Clinical
Modification), ICD-10, ICD-10-CM (International Classification of Diseases, 10th Revision),
Health Insurance Portability and Accountability Act (HIPAA), Health Information Technology
(HIT)
Clinical and Histological Effects of the
Intrathecal Administration of a Single Dose of
Dexmedetomidine in Rabbits
Authors: Ganem Eliana Marisa
Published: February 2021

Background: There is experimental evidence that dexmedetomidine has neuroprotective
effects. So, it could be expected that its intrathecal or epidural administration presents no
harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully
elucidated.
Objective: To evaluate the effect of preservative-free dexmedetomidine administered as a
subarachnoid single injection on the spinal cord and meninges of rabbits.
Study Design: Research article.
Setting: Experimental research laboratory.
Methods: Twenty young adult female rabbits, each weighing between 3200 and 4900 g,
and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9%
saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 μg). After intravenous
anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2
under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution
(saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under
medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion
was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and
histology was assessed using hematoxylin and eosin (HE) stain.
Results: None of the animals had impaired motor function or decreased nociception during
the period of clinical observation. None of the animals from the control group showed signs
of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with
signs of meningeal injury. The main histological changes observed were areas with meningeal
thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further
histological examination also revealed adherence areas among the pia and arachnoid. There
was no signal of injury in neural tissue in any animal of both groups.
Limitations: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine
was not performed.
Conclusion: On the basis of the present results, dexmedetomidine administered in the
subarachnoid space in a single dose of 10 µg is capable of producing histological changes over
the meninges of rabbits.
Key Words: Anesthesia, spinal; dexmedetomine; injections, spinal; spinal cord; rabbits
Concern about the Expanding Prescription Drug
Epidemic: A Survey of Licensed Prescribers and
Dispensers
Authors: Wright Eric R.
Published: February 2021

Background: Prescription drug misuse and abuse has reached epidemic levels in the U.S., and
stands as a leading cause of death. As the primary gatekeepers to the medications contributing
to this epidemic, it is critical to understand the views of licensed health care professionals.
Objective: In this study, we examine health care professionals’ concern regarding prescription
drug abuse in their communities and the impact their concern has had on their prescribing and
dispensing practices.
Study Design: An online survey of licensed health care providers.
Setting: Conducted in Indiana.
Methods: This study was a state-wide evaluation of Indiana’s prescription drug monitoring
program. The questionnaire asked respondents how concerned they were about prescription
drug abuse in their community. Variation in the level of concern was examined using ordinary
least squares regression and information about the respondents’ demographic background
and clinical experience. In addition, we used logistic regression to examine whether concern
was associated with changing prescribing and/or dispensing behavior.
Results: The majority of providers indicated they were “moderately” or “extremely
concerned” about prescription drug abuse in their communities. The level of concern, however,
varied significantly by profession, with pharmacists, physicians, nurse practitioners/physician
assistants being more concerned than dentists. Additional analyses indicate that providers with
higher levels of concern were those who also reported recently changing their prescribing and/
or dispensing behavior.
Limitations: The voluntary nature and geographical focus of the study limits the
generalizability of the findings.
Conclusion: Concern about prescription drug abuse is generally high across the major health
care professions; however, a significant minority of providers, particularly among dentists,
expressed little or no concern about the epidemic. Increasing health care providers’ general
level of concern about prescription drug abuse may be an effective public health tool for
encouraging voluntary reductions in prescribing and/or dispensing controlled substances.
Key words: Attitudes of physicians, nurse practitioners, physician assistants, and dentists;
prescription drug misuse and abuse; prescribing practices; dispensing practices
SIRT1 Inhibits the Catabolic Effect of IL-1β
Through TLR2/SIRT1/NF-κB Pathway in Human
Degenerative Nucleus Pulposus Cells
Authors: Hu Zhenming
Published: February 2021

Background: Low back pain (LBP), one of the most prominent problems worldwide, lacks
effective disease-modifying medical therapy. Intervertebral disc degeneration (IVDD) is a major
cause of LBP, and proinflammatory cytokines are the key factors involved in the development
of IVDD-induced back pain. Sirtuin 1 (SIRT1) is implicated in the molecular control of aging and
immune responses in various diseases; however, its effect on IVDD is not clearly understood.
Objective: To investigate the effects of SIRT1 on proinflammatory stress and signal transduction
pathways induced by interleukin-1β (IL-1β) in human degenerative nucleus pulposus (NP) cells.
Study Design: Research study.
Setting: Chongqing Key Laboratory of Ophthalmology.
Methods: Anti-apoptotic and anti-catabolic effects of SIRT1 on IL-1β were investigated using
a three-dimensional cell culture model of prestimulated human NP cells transfected with a
lentiviral vector overexpressing SIRT1 or a small-interfering RNA (siRNA) against the gene
encoding SIRT1. In addition, molecular mechanisms underlying the association of SIRT1 with
Toll-like receptor-2 (TLR2) and nuclear factor kappa B (NF-κB) were investigated.
Results: Our results indicated that decreased SIRT1 expression was associated with IVDD.
Direct regulation of SIRT1 expression did not affect the synthesis of extracellular matrix (ECM).
However, SIRT1 overexpression mediated by the lentiviral vector suppressed IL-1β-induced
ECM degradation and cell apoptosis. In contrast, knockdown of the gene encoding SIRT1
by the siRNA increased MMP expression and cell apoptosis induced by IL-1β. Furthermore,
SIRT1 deacetylated RelA/p65 to inhibit the nuclear translocation of NF-κB, thus inhibiting
inflammation. On the other hand, IL-1β downregulated SIRT1 expression by activating TLR2.
However, inhibition of TLR2 expression by an siRNA did not inhibit IL-1β-induced nuclear
translocation of NF-κB.
Limitations: Limitations of this study were the in vitro study design and lack of in vivo
validation of the observed effects of SIRT1 on IVDD.
Conclusions: Our results indicated that SIRT1 exerted anti-inflammatory effects against IL-1βmediated degeneration of NP cells through the TLR2/SIRT1/NF-κB pathway, suggesting that it
could be used as a potential candidate for treating IVDD-mediated back pain.
Key words: SIRT1, TLR2, NF-κB, intervertebral disc degeneration
Complex Regional Pain Syndrome-Type
1 Presenting as deQuervain’s Stenosing
Tenosynovitis
Authors: Vas Lakshmi
Published: February 2021

Aim: To report the presentation of complex regional pain syndrome-1 (CRPS-1) as deQuervain’s
stenosing tenosynovitis (DQST).
Case report: A 24-year-old woman presented with 3-year history of clinical diagnostic criteria
(CDC) of CRPS-1. Conservative and surgical treatment for this as DQST had failed to relieve her.
We diagnosed the problem as CRPS-1with CDC as inflammatory manifestations of a mechanical
tendinoses of all her 5 digital tendons caused by movement of the fingers and hand tethered by
agonist (flexor)/ antagonist (extensor) muscles in co-contraction. Ultrasound guided dry needling
(USGDN) relaxed the muscles, replacing the abnormal agonist/antagonist co-contraction with
normal agonist/antagonist coordination. Resolution of tendinoses reversed the inflammation
causing the CDC. Six months later she leads normal personal and professional life, with reduction
of scores of painDetect (from 21 to 5), Patient Health Questionnaire (from 13 to 4), Disability of
arm, shoulder and hand from 70.8 to 25 and reversal of muscle abnormality characteristic of CRPS1 on Musculoskeletal Ultrasonography (MSKUSG).
Conclusion: We believe the primary pathology of CRPS-1 to be co-contraction of agonist
(flexor)/antagonist(extensor) muscles of digits resulting in tendinoses akin to DQST. CDC of CRPS
are actually inflammatory manifestations of tendinoses amenable to reversal by USGDN which also
addresses the disability, a hallmark of CRPS.
Key words: Complex regional pain syndrome-1 (CRPS-1), deQuervain’s stenosing tenosynovitis
(DQST), neuropathy, co-contraction, dry needling (DN), ultrasound guided dry needling (USGDN),
musculoskeletal ultrasonography (MSKUSG)
Percutaneous Endoscopic Lumbar Discectomy
for L5-S1 Disc Herniation: Consideration of the
Relation between the Iliac Crest and L5-S1 Disc
Authors: Choi Kyung-Chul
Published: February 2021

Background: Percutaneous transforaminal techniques for the treatment of lumbar disc
herniation have markedly evolved. Percutaneous endoscopic lumbar discectomy (PELD) for L5-S1
disc herniation is regarded as challenging due to the unique anatomy of the iliac crest, large facet
joint, and inclinatory disc space. Among these, the iliac crest is considered a major obstacle. There
are no studies regarding the height of the iliac crest and their appropriate procedures in PELD.
Objectives: This study discusses PELD for L5-S1 disc herniation and the appropriate approach
according to the height of iliac crest.
Study Design: Retrospective evaluation.
Methods: 100 consecutive patients underwent PELD via the transforaminal route for L5-S1 disc
herniation by a single surgeon. The study was divided into 2 groups: the foraminoplasty group
requiring foraminal widening to access the herniated disc and the non-foraminoplasty group
treated by conventional posterolateral access. Radiological parameters such as iliac height, the
relative position of the iliac crest to the landmarks of the L5-S1 level, iliosacral angle and foraminal
height, and disc location were considered. Clinical outcomes were assessed by the Visual Analogue
Scale (VAS, 0 – 10) for back and leg pain, the Oswestry Disability Index (ODI, 0 – 100%), and the
modified MacNab criteria.
Results: The overall VAS scores for back and leg pain decreased from 6.0 to 2.3 and from 7.5
to 1.7. The mean ODI (%) improved from 54.0 to 11.6. Using modified MacNab criteria, a good
outcome was 92%. Foraminoplasty was required in 19 patients. Iliac crest height was significantly
higher in the foraminoplasty group than the non-foraminoplasty group (37.7 mm vs 30.1 mm,
P < 0.001). In the foraminoplasty group, the iliac crest is above the mid L5 pedicle on lateral
radiography in all cases. There were no significant differences in foraminal height, foraminal width,
iliosacral angle, or disc height between the 2 groups. In addition, there were no differences in
clinical outcome between the 2 groups.
Limitations: This study is a retrospective analysis and simplifies the complexity of the L5-S1 level
and iliac bone using two-dimensional radiography.
Conclusion: In high iliac crest cases where the iliac crest is above the mid L5 pedicle in lateral
radiography, foraminoplasty may be considered for transforaminal access of L5-S1 disc herniation.
Conventional transforaminal access can be utilized with ease in low iliac crest cases where the iliac
crest is below the mid-L5 pedicle.
Key words: Percutaneous endoscopic lumbar discectomy, transforaminal, L5-S1, iliac crest,
foraminoplasty
The Efficacy of Preoperative Gabapentin in
Spinal Surgery: A Meta-Analysis of Randomized
Controlled Trials
Authors: Ma Xin-long
Published: February 2021

Background: Pain management after spinal surgery has been studied for years. Gabapentin is
a third-generation antiepileptic drug that selectively affects the nociceptive process and has been
used for pain relief after surgery. However, the relationship between gabapentin and postoperative
pain in spinal surgery is still controversial.
Objective: To assess the efficacy of the pre-emptive use of gabapentin in spinal surgery.
Study Design: A meta-analysis of randomized controlled studies.
Setting: The MEDLINE, EMBASE, ClinicalTrials.gov, and Web of Science databases were
systematically searched.
Methods: This meta-analysis of randomized controlled trials (RCTs) was performed to compare
the use of gabapentin with placebo in spinal surgery regarding to the following: the mean
difference (MD) of postoperative opioid requirements, the changes of visual analog scale (VAS)
scores in 2 groups, and the incidence rate of adverse effects. An electronic-based search of all
related literatures was conducted, and only RCTs for spinal surgery were included. The MD of
postoperative opioid requirements and VAS scores and the relative risk (RR) of the incidence rate
of adverse effects in the gabapentin group versus the placebo group were extracted throughout
the study.
Results: Ten trials, involving 827 patients, met the inclusion criteria and were included in this
meta-analysis. The total morphine consumption was significantly lower over the first 24 hours
postoperatively in the gabapentin group (P < 0.05). The VAS scores at 2, 4, 6, 12, and 24 hours
were less in the gabapentin group (P < 0.05). The incidence rate of vomiting, pruritus, and urinary
retention was significantly less in the gabapentin groups (RR = 0.53, 95% CI 0.32–0.86, P < 0.05;
RR = 0.38, 95% CI 0.22–0.66, P < 0.05; RR = 0.57, 95% CI 0.34–0.98, P < 0.05, respectively).
Limitations: All of the studies we screened were published online except for unpublished
articles. Only 10 RCTs met our inclusion criteria, so the sample size was still relatively small.
Conclusion: This meta-analysis suggests that the administration of gabapentin is effective in
reducing postoperative opioid consumption, VAS scores, and some side effects after spinal surgery.
Key words: Gabapentin, analgesia, spinal surgery, meta-analysis, randomized controlled trials,
visual analog scale score, side effect
Analysis of Reporting Bias in Vertebral
Augmentation
Authors: Beall Douglas P.
Published: February 2021

Osteoporotic vertebral compression fractures (OVCFs) are a significant cause of
morbidity and mortality in the United States and worldwide, with estimates of 750,000
to 1.5 million occurring annually. As the elderly population continues to increase, the
incidence of OVCFs will continue to rise, as will the morbidity and mortality associated
with this condition. Vertebral augmentation (VA) was almost universally accepted
as the appropriate treatment modality prior to 2 sham trials published in 2009 by
the New England Journal of Medicine (NEJM). Subsequently, there is now significant
controversy regarding the optimal treatment of OVCFs. Since 2009 there have been
6 prospective randomized controlled studies (PRCTs) and 2 meta-analyses on VA for
the treatment of OVCFs. Five of the PRCTs and both of the meta-analyses have shown
superior results with VA as compared with nonsurgical management (NSM).
However, a recent health technology assessment and review article continue to overemphasize the 2 NEJM sham trials, despite the most current literature. These are
examples of inconsistent or biased data reporting with overemphasis on certain trial
types and exclusion of other types of data, resulting in the reporting of conclusions
that are partially representative or not representative of the complete data. As clinical
investigators, we have a responsibility to limit bias and ensure that the appropriate
treatment modalities are made available to vulnerable populations.
The aim of this perspective analysis is to examine sources of bias in reporting and
some of the publications that contain it, along with comparing the publications to the
current body of published literature relevant to this topic.
Key words: Vertebral augmentation, vertebroplasty, kyphoplasty, bias, osteoporosis,
compression fracture
Lower Cutoffs for LC-MS/MS Urine Drug Testing
Indicates Better Patient Compliance
Authors: Krock Kevin
Published: February 2021

Background: Urine drug testing is used by health care providers to determine a patient’s
compliance to their prescribed regimen and to detect non-prescribed medications and illicit drugs.
However, the cutoff levels used by clinical labs are often arbitrarily set and may not reflect the urine
drug concentrations of compliant patients.
Objectives: Our aim was to test the hypothesis that commonly used cutoffs for many prescribed
and illicit drugs were set too high, and methods using these cutoffs may yield a considerable
number of false-negative results. The goals of this study were to outline the way to analyze patient
results and estimate a more appropriate cutoff, develop and validate a high sensitivity analytical
method capable of quantitating drugs and metabolites at lower than the commonly used cutoffs,
and determine the number of true positive results that would have been missed when using the
common cutoffs.
Study Design: This was a retrospective study of urine specimens submitted for urine drug
testing as part of the monitoring of prescription drug compliance described in chronic opioid
therapy treatment guidelines.
Setting: The study was set in a clinical toxicology laboratory, using specimens submitted for
routine analysis by health care providers in the normal course of business.
Methods: Lognormal distributions of test results were generated and fitted with a trendline to
estimate the required cutoff level necessary to capture the normal distributions of each drug for
the patient population study. A validated laboratory derived liquid chromatography tandem mass
spectrometry (LC-MS/MS) analysis capable of achieving the required cutoff levels was developed
for each drug and/or metabolite.
Results: The study shows that a lognormal distribution of patient urine test results fitted with
a trendline is appropriate for estimating the required cutoff levels needed to assess medication
adherence. The study showed a wide variation in the false-negative rate, ranging from 1.5% to
94.3% across a range of prescribed and illicit drugs.
Limitations: The patient specimens were largely sourced from patients in either a long-term
pain management program or in treatment for substance use disorder in the US. These specimens
may not be representative of patients in other types of treatment or in countries with different
approaches to these issues.
Conclusions: The high-sensitivity method reduces false-negative results which could negatively
impact patient care. Clinicians using less sensitive methods for detecting and quantifying drugs and
metabolites in urine should exercise caution in assessing patient adherence using and changing the
treatment plan based on those results.
Key words: Urine drug testing, patient adherence, clinical toxicology, immunoassay, LC-MS,
definitive drug testing, REMS, negative test results, false negative
Toxicity Effects of Methylene Blue on Rat
Intervertebral Disc Annulus Fibrosus Cells
Authors: Zhang Liang
Published: February 2021

Background: There is an increasing local application of methylene blue (MB) in the treatment
of discogenic low back pain (LBP) and percutaneous transforaminal endoscopic discectomy
(PTED) procedures. MB could generate DNA damage and induce apoptosis in different cell types;
however, the effects of MB on intervertebral disc (IVD) annulus fibrosus (AF) cells are not clearly
understood.
Objective: The objective of this study was to investigate the effects of different concentrations
of MB on rat AF cells in vitro.
Study Design: This study used an experimental design.
Setting: This research was conducted at the Orthopaedic Institute of the Clinical Medical College
of Yangzhou University.
Methods: AF cells were isolated and cultured with different concentrations of MB (0, 2, 20, and
200 μg/mL) and assessed to determine the possible cytotoxic effects of MB. The cell proliferation
was detected by Cell Counting Kit-8 (CCK-8) assay. The inverted phase-contrast microscopy
was used to perform morphological observation of apoptotic cells, and flow cytometry was
used to measure the incidence of cell apoptosis. The mRNA and protein expression levels of
apoptosis-associated genes (caspase-3, Bcl-2, and Bax) and other related genes (collagen type
I, transforming growth factor β1 [TGF-β1], fibroblast growth factor [bFGF], and tissue inhibitor
of metalloproteinase-1 [TIMP-1]) were analyzed by quantitative real-time PCR (RT-PCR) and
Western blotting.
Results: Our results indicated that MB reduced cell viability in a concentration- and timedependent manner. MB also induced marked AF cell apoptosis in a concentration-dependent
manner observed by inverted phase-contrast microscopy, flow cytometry, and indicated by the
increased expression of caspase-3. Both RT-PCR and Western blotting revealed significant upregulation of Bax and caspase-3 expression levels accompanied by decreased expression of Bcl2 in a concentration-dependent manner. Moreover, collagen type I, TGF-β1, bFGF, and TIMP-1
mRNA and protein levels were also found to be decreased by MB in a concentration-dependent
manner.
Limitations: Limitations of this study were the in vitro study design and lack of in vivo validation
of the observed effects of MB on human IVD cells.
Conclusions: Our results indicate that a high concentration of MB can not only inhibit proliferation
and paracrine function of AF cells, but can also induce cell apoptosis in a concentration-dependent
manner, suggesting that it is necessary to choose low concentrations of MB in practical application
and limit the use of MB in the treatment of discogenic LBP to research protocols.
Key words: Methylene blue, annulus fibrosus cell, proliferation, apoptosis, paracrine
Comparison of Intravascular Injection Rate
Between Blunt and Sharp Needles During
Cervical Transforaminal Epidural Block
Authors: Kim Saeyoung
Published: February 2021

Background: Cervical transforaminal epidural block (CTEB) is a useful option in the
diagnosis and treatment of cervical radicular pain. However, inadvertent intravascular
injection can lead to severe neurologic complications. Blunt needles are considered to
displace instead of penetrate vessels because of their dull needle tip.
Objectives: To investigate whether there is a difference between blunt and sharp needles
in intravascular injection rates during CTEB.
Study Design: Prospective, randomized, clinical trial.
Setting: A tertiary hospital in South Korea.
Methods: After institutional review board approval, 108 patients undergoing CTEB for
treatment of radicular pain resulting from spinal stenosis and herniated nucleus pulposus
were randomly assigned to one of 2 needle groups (blunt needle or sharp needle). The
needle position was confirmed using biplanar fluoroscopy, and 2 mL of nonionic contrast
medium was injected to detect intravascular injection. Intravascular injection was defined as
the contrast medium spreading out through the vascular channel during injection under realtime fluoroscopy. This study was registered in ClinicalTrials.gov.
Results: The intravascular injection rate was not significantly different between the blunt
needle and sharp needle groups (35.2% vs. 33.3%, P > 0.05). The procedure time was
longer in the blunt needle group than in the sharp needle group (101.00 ± 12.4 seconds vs.
56.67 ± 8.3 seconds, P < 0.001).
Limitations: This was a single-center study. Additionally, the physicians could not be
blinded to the type of needle used.
Conclusions: In the present study, use of a blunt needle did not reduce the rate of
intravascular injection during CTEB compared to use of a sharp needle. In addition, procedure
time significantly increased with blunt needle use compared to sharp needle use.
Key words: Analgesia, bleeding, blunt needle, cervical spine, clinical trials, complications,
intravascular injection, radiculopathy, sharp needle, transforaminal epidural block
Paravertebral Dexmedetomidine in VideoAssisted Thoracic Surgeries for Acute and
Chronic Pain Prevention
Authors: Kamel Emad Zarief
Published: February 2021

Background: Video-assisted thoracoscopic surgery (VATS) is considered as one of the minimally
invasive surgeries. Early postoperative pain alleviation is very important to avoid complications, at
the same time, proper early pain control is an established fact to decrease the incidence of chronic
pain.
Objectives: To evaluate the efficacy of thoracic paravertebral block (PVB) by a bupivacaine/
dexmedetomidine mixture on acute and chronic post-thoracoscopic surgery pain in patients
undergoing VATS.
Study Design: A randomized prospective double-blinded trial.
Setting: Assiut University Hospitals, Orman Cardiology Hospital.
Methods: Sixty adult patients underwent elective VATS surgery under general anesthesia randomly
allocated into 2 groups; Group I received thoracic PVB with isobaric bupivacaine 0.5% (0.3 mL/
kg) and Group II received PVB with isobaric bupivacaine 0.5% (0.3 mL/kg) and dexmedetomidine
(1 mcg/kg). Postoperative pain (at rest, with cough, and with movement) was assessed through
a visual analog scale (VAS) every 30 minutes in the first 2 hours, then at the second, fourth,
eighth, and 24th hours. Time to first analgesia request and consumption of intravenous rescue
analgesia (ketorolac tromethamine 30 mg/dose) was recorded. Follow-up of the patients regarding
the incidence of chronic post-thoracoscopic pain by the end of the third and sixth months after
the procedure was reviewed through the Leeds Assessment of Neuropathic Symptoms and Signs
(LANSS) pain scale.
Results: VAS score was significantly lower in Group II during the early postoperative 90 minute
records. Pain with cough and with movement persisted to be significantly lower in Group II up
to the second postoperative hour. Time to first analgesia requirement was significantly longer in
Group II in comparison to Group (P < 0.001). There was less ketorolac consumption in Group II
than in Group I (P = 0.002). At the third month, Group II showed significantly lower incidence of
LANSS pain scale than Group I (P = 0.04).
Limitations: There was the heterogeneity of surgical procedures in the patients.
Conclusions: Dexmedetomidine as an adjuvant to bupivacaine PVB offers better pain relief
during the early postoperative hours, and it carries a favorable effect on chronic postoperative
pain.
Clinical trial registry number: NCT03632161.
Key words: Dexmedetomidine, paravertebral block, video-assisted thoracoscopic surgery,
postoperative pain, chronic pain
New Strategy for Minimally Invasive
Endoscopic Surgery to Treat Infectious
Spondylodiscitis in the Thoracolumbar Spine
Authors: Chen Hsien-Te
Published: February 2021

Background: Eradicating infection, protecting neurologic function, and maintaining structural
alignment are the 3 objectives of treatment for infectious spondylodiscitis. For some patients,
surgery may be necessary to achieve these goals; however, open surgeries are associated
with high morbidity and mortality in elderly patients and those with multiple comorbidities.
Endoscopic surgery provides a minimally invasive surgical option for obtaining a culture sample
to aid identification of pathogens, while also providing a route for adequate decompression
and drainage. The clinical results of this study were analyzed.
Objectives: To evaluate the efficacy and safety of spinal endoscopic surgery, the basic
characteristics of patients analyzed and their inflammatory markers, pain levels, and local
kyphotic angles were recorded before surgery and at regular intervals after surgery. The patients’
cultured pathogens and previous antibiotic treatments were also recorded and analyzed.
Study Design: Retrospective observational study (institutional review board: CMUH
105-REC2-101).
Setting: Inpatient surgery center.
Methods: From October 2006 to March 2017, of 508 patients who received spinal endoscopic
surgery, 60 with infectious spondylodiscitis were treated using this new strategy. All 60 patients
underwent plain film radiography and enhanced magnetic resonance imaging of the affected
region to obtain evidence of infectious spondylodiscitis. The role of a computed tomographyguided biopsy and some indications for open surgery were replaced with endoscopic surgery.
Results: All the patients reported rapid pain relief after endoscopic surgery and antibiotic
treatment. No significant changes in sagittal alignment were observed in final follow-up
radiography images. Causative pathogens were identified in 34 patients (culture rate: 77.27%)
without previous antibiotic treatment. The patients’ erythrocyte sedimentation rates and
C-reactive protein levels had decreased significantly 3 months after endoscopic surgery. Two
patients (3.3%) experienced infection relapse following initial endoscopic surgery; both of
them were efficiently resolved through a second round of endoscopic surgery. No surgeryrelated complications were observed and no open spinal surgery was required during the
follow-up period.
Limitations: This was a retrospective study; bias was unavoidable because of the singlecenter nature of the study design.
Conclusions: Regarding the culture rate, recurrence rate, kyphotic change, and surgeryrelated complications, this new strategy for endoscopic surgery is safe and effective for treating
infectious spondylodiscitis in the thoracic or lumbar spine and may be considered a new trend
in treating diseases of this type.
Key words: Spine, endoscopic, discectomy, spondylodiscitis, minimally invasive surgery
Transforaminal Endoscopic Lumbar Discectomy
Versus Open Lumbar Microdiscectomy: A
Comparative Cohort Study with a 5-Year
Follow-Up
Authors: Ahn Yong
Published: February 2021

Background: Transforaminal endoscopic lumbar discectomy (TELD) is regarded as an
effective treatment option for soft lumbar disc herniation (LDH). There have been few studies
evaluating the long-term outcomes of endoscopic procedures compared with conventional
surgery.
Objectives: The objective of this study was to demonstrate the clinical outcomes of TELD
compared with those of open lumbar microdiscectomy.
Study Design: Between January 2009 and September 2011, 335 consecutive patients
with symptomatic LDH were treated with decompressive discectomy, either TELD or open
microdiscectomy. Patients were prospectively entered into the clinical database and their
records were retrospectively reviewed.
Setting: Hospital and outpatient surgical center.
Methods: Data from 298 patients who were treated with decompressive discectomy, either
TELD or open microdiscectomy, were evaluated with a minimum 5-year follow-up period.
Among them, 146 patients were treated using TELD (TELD group), and the remaining 152
patients using open microdiscectomy (Open group). Perioperative data and clinical outcomes
were evaluated using the visual analog scale (VAS), the Oswestry Disability Index (ODI), and
the modified Macnab criteria.
Results: The VAS and ODI significantly improved in both groups. The rate of excellent or
good outcomes was 88.36% and 87.5% in the TELD and Open group, respectively. The
reoperation rate was 4.2% and 3.3% in the TELD and Open group, respectively. There were
no significant differences in the clinical outcomes; however, operative time, hospital stay, and
time to return to work were significantly shorter in the TELD group (P < 0.01).
Limitations: First, the patient selection was not randomized; therefore, the risk of bias
might be increased. Second, this study lacks analysis of the radiographic changes related to
the degenerative change over the long-term follow-up period.
Conclusions: The long-term results of TELD for soft LDH are comparable to those of
conventional open microdiscectomy. The selective endoscopic discectomy technique under
local anesthesia provides the typical advantages of minimally invasive procedures such as a
shorter operation time, hospital stay, and recovery time.
Key words: Endoscopic, discectomy, hospital stay, lumbar disc, microscopic, operative time,
return to work, transforaminal
Percutaneous Endoscopic Debridement and
Drainage for Spinal Infection: Systemic Review
and Meta-Analysis
Authors: Cui Xingang
Published: February 2021

Background: Percutaneous endoscopic debridement and drainage (PEDD) has played a vital role in
the management of spinal infection; however, limited PEDD results are available to date.
Objectives: The purpose of this systematic review is to examine the existing literature, to give an
objective estimate of the outcomes of PEDD using a meta-analytical approach.
Study Design: Meta-analysis and systematic review of retrospective single-arm studies.
Methods: A comprehensive online review was performed in MEDLINE, EMBASE, PubMed, Web of
Science, and Cochrane databases from 1980 to October 2018. Eligible studies included the singlearm studies that mentioned PEDD in the management of spinal infection. Pooled event rates for
positive bacteria culture, pain control satisfaction, and reoperation were estimated. The complications
of PEDD were also recorded.
Results: Nine single-arm PEDD articles (158 patients) were included. The pooled event rate was
82% (95% CI: 75%-88%) for positive bacteria culture, 81% (95% CI: 73%-87%) for pain control
satisfaction, and 21% (95% CI: 15%-29%) for reoperation. There are few complications reported in
the literature that included transient paresthesia in the affected lumbar segment and local kyphosis.
Limitations: First, all included studies were retrospective series with inherent methodological
limitations. Second, the sample size and the number of studies that were found to be eligible was
small. In addition, all included studies are single-arm, and further studies are necessary in large
randomized controlled trials on comparing the efficacy of conservative therapy, PEDD, and open
surgical intervention.
Conclusions: PEDD not only has a high rate of causative-pathogen identification, but also provides
satisfactory clinical outcome. Early PEDD intervention in spinal infection is encouraging; however,
further studies in large randomized controlled trials on comparing the efficacy of conservative
therapy, PEDD, and open surgical intervention are necessary.
Key words: Percutaneous endoscopic debridement and drainage, spinal infection, meta-analysis
Full-Endoscopic Lumbar Fusion Outcomes
in Patients with Minimal Deformities: A
Retrospective Study of Data Collected Between
2011 and 2015
Authors: Kamson Solomon
Published: February 2021

Background: Open transforaminal lumbar interbody fusion (TLIF) is the gold standard treatment
for back pain due to degenerative disc disease and lumbar instability. Traditional open TLIF has been
associated with extensive tissue dissection, excessive blood loss, and slow recovery time. Full-endoscopic
transforaminal lumbar interbody fusion (FE-TLIF) is an evolving treatment.
Objectives: This study aims to review outcomes of FE-TLIF performed in an ambulatory surgery center
(ASC) on patients with advanced disc disease with minimal spinal deformity.
Study Design: This study employed a retrospective cohort design.
Methods: This Western Institutional Review Board-approved study (#1-925640-1) assessed blood loss,
operative time (OR time), post anesthesia care unit time (PACU time), and Visual Analog Scale (VAS)
of 85 patients who underwent FE-TLIF between 2011 and 2015 and were followed up for 12 months.
Relationships between risk factors (demographics, clinical presentation) and outcomes were analyzed.
Results: No intraoperative complications were observed. There were 2 cases of postoperative
sympathetically mediated pain and 3 reoperations. The number of decompression/fusion levels was
crucial to OR time but had a smaller impact on PACU time. OR time for patients with 2-level fusion was
110 minutes longer than for those with one level operation. BMI and age had no significant effect on OR
time. BMI had a modest effect on PACU time. Gender and age did not affect PACU time. A significant
decrease in VAS was observed.
Limitations: This study has several limitations, including the lack of a control group and reliance
on patient-reported outcomes (VAS). In addition, fusion rate and global sagittal alignment were not
measured. Although not statistically significant, the use of facet screws, unilateral, or bilateral pedicle
screws presented variation in techniques within the group. Early recovery also diminished the incentive
for long-term follow-up.
Conclusion: FE-TLIF is a feasible technique for lumbar stabilization surgery in an ASC in select patients.
This level-II study demonstrates safety in a variety of clinical presentations, including obesity, extremes
of age, and anatomical access challenge. Larger clinical series are necessary to validate this technique,
particularly for the treatment of patients with advanced spinal deformities.
Key words: Full-endoscopic, minimally invasive spine surgery, postoperative complications,
TLIF, lumbar fusion, low back pain