Spinal Sites Research Articles

Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury

BackgroundThe acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord.MethodsAdult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate.ResultsSCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself.ConclusionsOur data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.

A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord.

In mammals, perivascular cell-derived scarring after spinal cord injury impedes axonal regrowth. In contrast, the extracellular matrix (ECM) in the spinal lesion site of zebrafish is permissive and required for axon regeneration. However, the cellular mechanisms underlying this interspecies difference have not been investigated. Here, we show that an injury to the zebrafish spinal cord triggers recruitment of pdgfrb+ myoseptal and perivascular cells in a PDGFR signaling-dependent manner. Interference with pdgfrb+ cell recruitment or depletion of pdgfrb+ cells inhibits axonal regrowth and recovery of locomotor function. Transcriptional profiling and functional experiments reveal that pdgfrb+ cells upregulate expression of axon growth-promoting ECM genes (cthrc1a and col12a1a/b) and concomitantly reduce synthesis of matrix molecules that are detrimental to regeneration (lum and mfap2). Our data demonstrate that a switch in ECM composition is critical for axon regeneration after spinal cord injury and identify the cellular source and components of the growth-promoting lesion ECM.

Enriched conditioning expands the regenerative ability of sensory neurons after spinal cord injury via neuronal intrinsic redox signaling

Overcoming the restricted axonal regenerative ability that limits functional repair following a central nervous system injury remains a challenge. Here we report a regenerative paradigm that we call enriched conditioning, which combines environmental enrichment (EE) followed by a conditioning sciatic nerve axotomy that precedes a spinal cord injury (SCI). Enriched conditioning significantly increases the regenerative ability of dorsal root ganglia (DRG) sensory neurons compared to EE or a conditioning injury alone, propelling axon growth well beyond the spinal injury site. Mechanistically, we established that enriched conditioning relies on the unique neuronal intrinsic signaling axis PKC-STAT3-NADPH oxidase 2 (NOX2), enhancing redox signaling as shown by redox proteomics in DRG. Finally, NOX2 conditional deletion or overexpression respectively blocked or phenocopied enriched conditioning-dependent axon regeneration after SCI leading to improved functional recovery. These studies provide a paradigm that drives the regenerative ability of sensory neurons offering a potential redox-dependent regenerative model for mechanistic and therapeutic discoveries.

Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in rats.

Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords.

Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain.

Adenosine is a purine nucleoside, responsible for the regulation of multiple physiological and pathological cellular and tissue functions by activation of four G protein-coupled receptors (GPCR), namely A1, A2A, A2B, and A3 adenosine receptors (ARs). In recent years, extensive progress has been made to elucidate the role of adenosine in pain regulation. Most of the antinociceptive effects of adenosine are dependent upon A1AR activation located at peripheral, spinal, and supraspinal sites. The role of A2AAR and A2BAR is more controversial since their activation has both pro- and anti-nociceptive effects. A3AR agonists are emerging as promising candidates for neuropathic pain. Although their therapeutic potential has been demonstrated in diverse preclinical studies, no AR ligands have so far reached the market. To date, novel pharmacological approaches such as adenosine regulating agents and allosteric modulators have been proposed to improve efficacy and limit side effects enhancing the effect of endogenous adenosine. This review aims to provide an overview of the therapeutic potential of ligands interacting with ARs and the adenosinergic system for the treatment of acute and chronic pain.

Intrathecal Delivery of BDNF Into the Lumbar Cistern Re-Engages Locomotor Stepping After Spinal Cord Injury.

Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors administration has been shown to promote recovery of locomotion in the absence of locomotor training in adult spinalized animals. These delivery methods involved risks of secondary injury to the cord and do not allow for precise and controlled dosing making them unsuitable for clinical applications. The present study was aimed at evaluating the locomotor recovery efficacy and safety of the neurotrophin BDNF delivered intrathecally to the lumbar locomotor centers using an implantable and programmable infusion mini-pump. Results showed that BDNF treated spinal cats recovered weight-bearing plantar stepping at all velocities tested (0.3-0.8 m/s). Spinal cats treated with saline did not recover stepping ability, especially at higher velocities, and dragged their hind paws on the treadmill. Histological evaluation showed minimal catheter associated trauma and tissue inflammation, underlining that intrathecal delivery by an implantable/programmable pump is a safe and effective method for delivery of a controlled BDNF dosage; it poses minimal risks to the cord and is clinically translational.

Spinal Cord Imaging Markers and Recovery of Volitional Leg Movement With Spinal Cord Epidural Stimulation in Individuals With Clinically Motor Complete Spinal Cord Injury.

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

Scenario of General Anesthesia for Cesarean Section in Rural Tertiary Care Center in High Altitude Karnali Academy of Health Sciences

Background: General anesthesia for cesarean section is being less popular for cesarean section in present days but sometime general anesthesia is inevitable. The aim of the study is to assess the trends of general anesthesia, indications, clinical outcome in mother and fetus in high altitude setting of tertiary care center of Nepal.
 Methods: We conducted descriptive cross-sectional study all cases of cesarean section in Karnali Academy of health Sciences (KAHS) located at high altitude over three years period in our institute. Data were retrieved from the hospital records during three fiscal year (Jan 1st 2017 to Jan Dec 31st 2019). The record of all the patients who underwent cesarean section under general anesthesia was reviewed for demographic details, indication of general anesthesia, trends for general and spinal anesthesia and maternal and neonatal outcome.
 Results: Out of total deliveries 2175, 309 (14.2%) cases account for cesarean section. Among them, 52 (17%) required general anesthesia . Eclampsia 19(36%) remain the major indication for General Anesthesia in cesarean section followed by failure of spinal anesthesia number 14 (26%) , cord prolapse six (12%), antepartam haemorrhage five (10%), spinal site infection four (8%), Khiphoscoliosis two(4%), Patients request two (4%). Use for general anesthesia technique was consistent for three years with slow rise in use of spinal anesthesia . There was no any anesthesia related maternal mortality and nine intraoperative neonatal 
 Conclusions: General anesthesia practices are consistently required in rural high-altitude setup. Eclampsia is the commonest indication followed by failure of spinal anesthesia and cord prolapse. Neonatal outcome is still not good.

Interactive Mechanisms of Supraspinal Sites of Opioid Analgesic Action: A Festschrift to Dr. Gavril W. Pasternak.

Almost a half century of research has elaborated the discoveries of the central mechanisms governing the analgesic responses of opiates, including their receptors, endogenous peptides, genes and their putative spinal and supraspinal sites of action. One of the central tenets of "gate-control theories of pain" was the activation of descending supraspinal sites by opiate drugs and opioid peptides thereby controlling further noxious input. This review in the Special Issue dedicated to the research of Dr. Gavril Pasternak indicates his contributions to the understanding of supraspinal mediation of opioid analgesic action within the context of the large body of work over this period. This review will examine (a) the relevant supraspinal sites mediating opioid analgesia, (b) the opioid receptor subtypes and opioid peptides involved, (c) supraspinal site analgesic interactions and their underlying neurophysiology, (d) molecular (particularly AS) tools identifying opioid receptor actions, and (e) relevant physiological variables affecting site-specific opioid analgesia. This review will build on classic initial studies, specify the contributions that Gavril Pasternak and his colleagues did in this specific area, and follow through with studies up to the present.

Spinal Surgery Site Infection Leading to Implant Loosening Is Influenced by the Number of Prior Operations

Study Design:Retrospective Cohort Study.Objectives:Spinal surgery site infection and chronic implant infection are possible causes for ongoing pain, implant loosening, and failed back surgery syndrome. Evidence of chronic infection was found in 29.1% of revision cases but is also found in a considerable number of degenerative cases without prior surgery. Infection mechanisms and possible clinical correlations are unclear.Methods:Retrospective analysis of standardized surgery site screening (swab, tissue samples, implant sonication) in 181 cases without clinical evidence of preoperative surgery site infection.Results:Screening results of cases without prior spinal surgery (n = 49, 10.2% positive) were compared to cases with prior spine surgery without implant placement (e.g. micro discectomy) (n = 21, 23.8% positive), revision cases following singular spinal fusion (n = 73, 23.2% positive), and cases with multiple revisions (n = 38, 50.0% positive). Propionibacterium spp. detection rate increased to 80% in positive cases with multiple revisions. Implants in place during revision surgery had a significantly higher infection rate (32.4%) compared to no implant (14.2%, p = 0.007). Positive cases had a significantly higher pain level prior to surgery compared to negative cases (p = 0.019). Laboratory parameters had no predictive value. Logistic regression revealed that previous spinal surgeries (odds ratio [OR] 1.38 per operation, p < 0.001) and male sex (OR 1.15, p = 0.028) were independent predictive factors for infection.Conclusions:Previous spinal surgery is a risk factor for chronic surgery site infection, leading to chronic pain, implant loosening, and revision. The presence of Propionibacterium spp. was correlated with chronic implant loosening and was more likely with cumulative surgeries.

Nanoparticle-Based Estrogen Delivery to Spinal Cord Injury Site Reduces Local Parenchymal Destruction and Improves Functional Recovery.

Spinal cord injury (SCI) patients sustain significant functional impairments; this is causally related to restricted neuronal regeneration after injury. The ensuing reactive gliosis, inflammatory cascade, and glial scar formation impede axonal regrowth. Although systemic anti-inflammatory agents (steroids) have been previously administered to counteract this, no current therapeutic is approved for post-injury neuronal regeneration, in part because of related side effects. Likewise, therapeutic systemic estrogen levels exhibit neuroprotective properties, but dose-dependent side effects are prohibitive. The current study thus uses low-dose estrogen delivery to the spinal cord injury (SCI) site using an agarose gel patch embedded with estrogen-loaded nanoparticles. Compared to controls, spinal cords from rodents treated with nanoparticle site-directed estrogen demonstrated significantly decreased post-injury lesion size, reactive gliosis, and glial scar formation. However, axonal regeneration, vascular endothelial growth factor production, and glial-cell-derived neurotrophic factor levels were increased with estrogen administration. Concomitantly improved locomotor and bladder functional recovery were observed with estrogen administration after injury. Therefore, low-dose site-directed estrogen may provide a future approach for enhanced neuronal repair and functional recovery in SCI patients.

2021 Young Investigator Award Winner: Anatomic Gradients in the Microbiology of Spinal Fusion Surgical Site Infection and Resistance to Surgical Antimicrobial Prophylaxis.

Retrospective hospital-registry study. To characterize the microbial epidemiology of surgical site infection (SSI) in spinal fusion surgery and the burden of resistance to standard surgical antibiotic prophylaxis. SSI persists as a leading complication of spinal fusion surgery despite the growth of enhanced recovery programs and improvements in other measures of surgical quality. Improved understandings of SSI microbiology and common mechanisms of failure for current prevention strategies are required to inform the development of novel approaches to prevention relevant to modern surgical practice. Spinal fusion cases performed at a single referral center between January 2011 and June 2019 were reviewed and SSI cases meeting National Healthcare Safety Network criteria were identified. Using microbiologic and procedural data from each case, we analyzed the anatomic distribution of pathogens, their differential time to presentation, and correlation with methicillin-resistant Staphylococcus aureus screening results. Susceptibility of isolates cultured from each infection were compared with the spectrum of surgical antibiotic prophylaxis administered during the index procedure on a per-case basis. Susceptibility to alternate prophylactic agents was also modeled. Among 6727 cases, 351 infections occurred within 90 days. An anatomic gradient in the microbiology of SSI was observed across the length of the back, transitioning from cutaneous (gram-positive) flora in the cervical spine to enteric (gram-negative/anaerobic) flora in the lumbosacral region (correlation coefficient 0.94, P < 0.001). The majority (57.5%) of infections were resistant to the prophylaxis administered during the procedure. Cephalosporin-resistant gram-negative infection was common at lumbosacral levels and undetected methicillin-resistance was common at cervical levels. Individualized infection prevention strategies tailored to operative level are needed in spine surgery. Endogenous wound contamination with enteric flora may be a common mechanism of infection in lumbosacral fusion. Novel approaches to prophylaxis and prevention should be prioritized in this population.Level of Evidence: 3.

AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury

Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.

Taking a Deeper Dive; Mitigating Modifiable Risk Factors for Spinal Fusion Surgical Site Infections

<h3>Background</h3> Surgical Site Infections (SSIs) are serious complications of spinal fusion surgery. Identifying modifiable risk factors unique to this population can provide insight into prevention strategies. Evidence demonstrates that intradisciplinary process improvement teams can be helpful in identifying gaps in processes. <h3>Methods</h3> In response to a 12 month spinal fusion standardized infection ratio (SIR) of 3.0 (P=.003) we formed an interdisciplinary improvement team. Personnel representing all phase of surgery, infection prevention, infectious disease, and sterile processing were represented .Members assessed all elements of perioperative care to identify compliance with evidence based guidelines, cleaning and sterilization processes, postoperative management, and transitions of care. SSI data was presented and reviewed. A process flow map was used to identify risk points and gaps. As opportunities were identified, they were rank ordered based upon infection risk and likelihood of successful intervention. The top five issues were addressed and an implementation plan was developed. <h3>Results</h3> Review of records identified skin and fecal flora as predominate organisms. Gaps in timeliness of vendor tray delivery, inability to effectively clean kerrisons prior to sterilization, staff turnover for break relief during implantation, variations in skin prep and use of patient's dirty back braces brought from home were prioritized based upon the pre-established criteria.The following interventions were implemented: Chlorohexidine Body Wipe process in Pre-Op revised (Nose to Toes application) Vendor Consigned/Loaned Trays in Sterile Processing changed to required 48 hour turnaround OR staff scheduling adjustments for break and lunch relief Purchased take –apart Kerrison rongeurs New back braces were ordered for specified patients Fiscal year 2019 SIR decreased from 3.0 to 1.1 after interventions (P=.03) <h3>Conclusions</h3> Interdisciplinary teams are effective in identifying gaps in practice that are unique to specialized surgical populations. Interventions based upon process gaps can result in improved patient outcomes.

The κ-opioid receptor in opioid dependence

Opioid dependence that particularly mediates through the μ-opioid receptor remains a major concern of opioid analgesics. Drugs which interact with κ-opioid receptors are increasingly used as an alternative to μ- agonist analgesic. Several studies have reported that chronic administration of κ-opioid agonists such as U-50488H, U-69,593, and butorphanol also results in development of physical dependence/withdrawal. In addition, the ability of a highly selective κ-opioid antagonist, nor-binaltorphimine, given systemically or spinally, to precipitate withdrawal behaviors in opioid-dependent animals further demonstrates that both supraspinal and spinal sites of κ-opioid receptors play an important role in opioid dependence/withdrawal. With regard to the role of glutamate in opioid dependence/withdrawal, the κ-opioid receptor located at the presynaptic nerve terminal within the locus coeruleus crucially regulates glutamate release during the expression of opioid withdrawal. Physical dependence on κ-opioid agonists is associated with the downregulation and antagonist- sensitive state of the κ-opioid receptor in the spinal cord and specific brain areas. However, alterations of the κ-opioid receptor may not completely explain the mechanisms of dependence development. With cloned κ- opioid receptors recently available, it could be elucidated that the cellular and biological mechanisms of κ-opioid receptors for the development of dependence/withdrawal may differ from those of μ-opioid receptors.

Baicalin prevents the up-regulation of TRPV1 in dorsal root ganglion and attenuates chronic neuropathic pain.

BackgroundNeuropathic pain is a major public health problem because it has a considerable impact on life quality of patients. TRP channels from dorsal root ganglion (DRG) play a crucial role in facilitating pain transmission at peripheral and spinal sites. Baicalin has neuroprotective effects and improves the pathological and behavioural outcomes of various types of nerve injury. The present study aims to examine the analgesic effects of baicalin on chronic neuropathic pain.MethodsNeuropathic pain animal model was created by chronic constriction injury of the sciatic nerve (CCI). Behavioural tests were performed by von Frey and hot plate tests. mRNA and protein expression levels were examined by quantitative RT‐PCR and western blot.ResultsConsecutive intraperitoneal administration of baicalin for 16 days reduced the mechanical and thermal nociceptive responses induced by CCI surgery in a dose‐dependent manner. The mRNA expression levels of Trpv1 and Trpa1 were significantly increased in the DRG of CCI rats. Moreover baicalin administration reversed TRPV1 expression and phosphorylation of ERK in DRG neurons after peripheral nerve injury.ConclusionsOur results suggested that baicalin may ameliorate neuropathic pain by suppressing TRPV1 up‐regulation and ERK phosphorylation in DRG of neuropathic pain rats. Baicalin has a significant analgesic effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

Regional cerebral metabolic levels and turnover in awake rats after acute or chronic spinal cord injury.

Spinal cord injury (SCI) is a common cause of disability, which often leads to sensorimotor cortex dysfunction above the spinal injury site. However, the cerebral regional effects on metabolic information after SCI have been little studied. Here, adult Sprague-Dawley rats were divided into acute and chronic treatment groups and sham groups with day-matched periods. The Basso, Beatte, and Bresnahan scores method were utilized to evaluate the changes in behaviors during the recovery of the animals, and the metabolic information was measured with the 1 H-observed/13 C-edited NMR method. Total metabolic concentrations in every region were almost similar in both treated groups. However, the metabolic kinetics in most regions in the acute group were significantly altered (P<.05), particularly in the cortical area, thalamus and medulla (P<.01). After long-term recovery, some metabolic kinetics were recovered, especially in the temporal cortex, occipital cortex, and medulla. The metabolic kinetic changes revealed the alteration of metabolism and neurotransmission in different brain regions after SCI, which present evidence for the alternation of brain glucose oxidation. Therefore, this shows the significant influence of SCI on cerebral function and neuroscience research. This study also provides the theoretical basis for clinical therapy after SCI, such as mitochondrial transplantation.

Injectable Electrical Conductive and Phosphate Releasing Gel with Two-Dimensional Black Phosphorus and Carbon Nanotubes for Bone Tissue Engineering.

Injectable hydrogels have unique advantages for the repair of irregular tissue defects. In this study, we report a novel injectable carbon nanotube (CNT) and black phosphorus (BP) gel with enhanced mechanical strength, electrical conductivity, and continuous phosphate ion release for tissue engineering. The gel utilized biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) polymer as the cross-linking matrix, with the addition of cross-linkable CNT-poly(ethylene glycol)-acrylate (CNTpega) to grant mechanical support and electric conductivity. Two-dimensional (2D) black phosphorus nanosheets were also infused to aid in tissue regeneration through the steady release of phosphate that results from environmental oxidation of phosphorus in situ. This newly developed BP-CNTpega-gel was found to enhance the adhesion, proliferation, and osteogenic differentiation of MC3T3 preosteoblast cells. With electric stimulation, the osteogenesis of preosteoblast cells was further enhanced with elevated expression of several key osteogenic pathway genes. As monitored with X-ray imaging, the BP-CNTpega-gel demonstrated excellent in situ gelation and cross-linking to fill femur defects, vertebral body cavities, and posterolateral spinal fusion sites in the rabbit. Together, these results indicate that this newly developed injectable BP-CNTpega-gel owns promising potential for future bone and broad types of tissue engineering applications.

The association of tobacco smoking and bone health in the elderly population of Iran: results from Bushehr elderly health (BEH) program.

Smoking has been linked with osteoporosis, but further evidence is required, especially concerning the effects of different types of tobacco smoking. We sought to examine the association between smoking and bone health in a large cohort of elderly Iranians. The data from 2377 participants aged >60years of Bushehr Elderly Health (BEH) program were used. Regardless of the type of smoking, participants were initially classified as non-smokers, ex-smokers and current smokers. Current smokers were also categorized based on the smoking type (pure cigarette, pure hookah and both). Dual-energy X-ray absorptiometry was used to evaluate bone density as well as Trabecular Bone Score (TBS). T-score ≤ -2.5 in either of the femoral neck, total hip or spinal sites was applied to determine the osteoporosis. The association of smoking and osteoporosis was assessed using multivariable modified Poisson regression model and reported as adjusted prevalence ratios (APR). The linear regression model was used to assess the association between smoking and TBS, adjusting for potential factors. A total of 2377 (1225 women) were enrolled [mean age: 69.3 (±6.4) years], among which 1054 (44.3%) participants were nonsmokers. In all, 496 (20.9%) participants were current smokers. Multivariable regression analysis revealed no significant association between smoking (either current or past) and osteoporosis in women. In men, current smoking was negatively associated with osteoporosis (APR: 1.51, 95%CI: 1.16-1.96). Among current users, cigarette smoking was associated with osteoporosis (APR: 1.57, 95%CI: 1.20-2.03); however, we could not detect a significant association between current smoking of hookah and osteoporosis. In men, a significant association was also detected between current cigarette smoking and TBS (coefficient: -0.03, 95%CI: -0.01, -0.04). Current cigarette smoking is associated with both the quantity and quality of bone mass in elderly men. Although we could not detect a significant association between hookah and osteoporosis in men, considering the prevalence of hookah smoking in the middle eastern countries, further studies are needed to determine the effect of hookah smoking on bone health.

Whole Spine CT Scan for the Detection of Acute Spinal Fractures in Diffuse Idiopathic Skeletal Hyperostosis Patients Who Sustained Low-energy Trauma.

Retrospective cohort study. The aim of this study was to evaluate the role and value of whole-spine computerized tomography (WSCT) versus radiographs and targeted CT to tender spinal regions in patients with diffuse idiopathic skeletal hyperostosis (DISH) after low-energy trauma. Subjects with DISH are prone to spinal fractures even after low-impact trauma due to a rigid spinal structure. One-hundred forty-seven subjects (average age: 83 years, M:F 64/83) with verified DISH (Resnick and Niwayama radiographic criteria) on WSCT who were admitted to the emergency room (ER) after low-energy trauma and for whom there were radiographs of at least the thoracic and lumbar spine were evaluated for the presence of acute spinal fractures on both radiographs and WSCT. Agreement between fracture location and spinal tenderness location (cervical, thoracic, or lumbar) as reported in the medical record was evaluated. Significantly more acute fractures were detected on WSCT compared to radiographs (55 and 32, P < 0.00001, respectively). The site of tenderness was not indicative of the fractured spinal segment in 57% of all acute fractures (seven cervical, 15 thoracic, and 16 lumbar). No fracture was detected on WSCT in 10 subjects with an unspecified pain location. Multilevel distant fractures were detected in two patients with a specified pain location to only one of the fractures. WSCT in DISH subjects after low-impact trauma is mandatory due to the high prevalence of acute fractures and the low specificity for fracture detection on radiographs. A targeted CT approach to the tender spinal segment proved to be inadequate and would have missed 57% of the acute single fractures with incompatible spinal tenderness location. These results support the significant role of WSCT in the ER setting for detecting and pinpointing the spinal fracture site of DISH subjects who present with low-impact trauma. 3.