Teriparatide and bisphosphonate use in osteoporotic spinal fusion patients: a systematic review and meta-analysis.

PURPOSE: Osteoporosis is one of the most common conditions among adults worldwide. It also presents a challenge among patients undergoing spinal surgery. Use of Teriparatide and bisphosphonates in such patients has been shown to improve outcomes after fusion surgery, including successful fusion, decreased risk of instrumentation failure, and patient-reported outcomes. Herein, we performed a systematic review and indirect meta-analysis of available literature on outcomes of fusion surgery after use of bisphosphonates or Teriparatide. METHODS: We conducted a comprehensive search of all databases (Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) to identify studies assessing outcomes of spinal fusion among osteoporotic patients after use of Teriparatide or bisphosphonate. Four authors independently screened electronic search results, and all four authors independently performed study selection. Two authors performed independent data extraction and assessed the studies' risk of bias assessment using standardized forms of Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I). RESULTS: Nineteen studies were included in the final analysis. A total of 13 studies evaluated the difference in fusion rate between bisphosphonates and Teriparatide or control group. Fusion rate was higher for bisphosphonates (effect size (ES) 83%, 95% CI 77-89%) compared with Teriparatide (ES 71%, 95% CI 57-85%), with the p value for heterogeneity between groups without statistical significance (p = 0.123). Five studies assessed the impact of using bisphosphonate or Teriparatide on screw loosening. The rate of screw loosening was higher for bisphosphonates (ES 19%, 95% CI 13-25%) compared with Teriparatide (ES 13%, 95% CI 9-16%) without statistical significance (p = 0.52). CONCLUSION: Our results indicate that while both agents may be associated with positive outcomes, bisphosphonates may be associated with a higher fusion rate, while Teriparatide may be associated with lower screw loosening. The decision to treat with either agent should be tailored individually for each patient keeping in consideration the adverse effect and pharmacokinetic profiles.

Effects of teriparatide and bisphosphonate on spinal fusion procedure: A systematic review and network meta-analysis.

BACKGROUND: Giving patients anti-osteoporotic agents peri-operatively is a well-accepted strategy to increase fusion rate and prevent complications. The purpose of this study was to investigate effectiveness of teriparatide and bisphosphonate on fusion surgery of thoracic and lumbar spine. METHODS: We searched EMBASE and PubMed for randomized clinical trials (RCTs) and prospective comparative studies using teriparatide or bisphosphonate in peri-operative spinal fusion surgery. Our synthesized data of fusion rate, Oswestry disability index (ODI), and adverse event in contrast-based network meta-analysis. Pooled results were presented in risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: Our search hit eight RCTs and three prospective studies with 676 patients receiving spinal surgery. Pooled result showed that teriparatide+Denosumab leads to significantly higher fusion rate than placebo (RR, 2.84; 95% CI: 1.22 to 6.60) and bisphosphonate (RR, 2.59; 95% CI: 1.13 to 5.96). We did not observe significant finding among placebo, teriparatide, and bisphosphonate in the two network models. CONCLUSION: This is the first network meta-analysis providing an overview of the use of teriparatide and bisphosphonate for spinal fusion surgery. Teriparatide treatments are worth to be consider for spinal fusion surgery.

Association of Aspirin and Other Nonsteroidal Anti-inflammatory Drugs With Vertebral Trabecular Bone: Data From Multiethnic Study of Atherosclerosis, a Population-Based Multicenter Cohort Study.

OBJECTIVE: The objective of this article was to study the association of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with bone mineral density (BMD). METHODS: Spine BMD was evaluated in a subset of 2028 participants from the Multiethnic Study of Atherosclerosis cohort who were NSAID users (including aspirin) and underwent both lumbar and thoracic imaging. Multiethnic Study of Atherosclerosis is a prospective cohort study that includes 4 ethnic groups (white, Asian, African American, and Hispanic). Trabecular BMD was evaluated by quantitative computed tomography based on cardiac computed tomography images, which were obtained during coronary calcium scans. The analyses were cross sectional using baseline examination data for exposure and outcomes. RESULTS: After adjustment for potential confounders including age, sex, race, and traditional cardiovascular risk factors, a small association between trabecular BMD and baseline use of COX-2-selective NSAID was observed. COX-2-selective NSAID use was associated with 7.4 mg/cm (95% confidence interval [CI], 1.6-13.3; P = 0. 013) higher trabecular BMD in thoracic spine and 10.6 mg/cm higher at lumbar spine (95% CI, 5.1-16.1; P < 0.001). Among regular aspirin users, there was no association between drug use and trabecular BMD. Considering all spine fractures together, the prevalence ratio of fractures among aspirin users was 1.0 (95% CI, 0.6-1.6) and 1.1 (95% CI, 0.5-2.3) among COX-2-selective NSAID users. CONCLUSIONS: Regular use of aspirin has no significant association with trabecular BMD in either the thoracic or lumbar spine and no association with fracture prevalence. COX-2-selective NSAIDs may have modest positive association with BMD, but the mechanisms were not assessed and the observational study design makes residual confounding a possible alternate explanation. Potential pathological mechanisms warrant further longitudinal exploration.

The Novel Costotransverse Foramen Block Technique: Distribution Characteristics of Injectate Compared with Erector Spinae Plane Block.

BACKGROUND: The costotransverse foramen (CTF) is a space continuous with the paravertebral space. We hypothesized that injections passing through the CTF will result in a successful injectate spread to the paravertebral space. OBJECTIVES: We investigated patterns of dye spread to assess characteristics of neural blockade following ultrasound-guided CTF and erector spinae plane (ESP) injection in an anatomic and clinical study. STUDY DESIGN: Prospective cadaveric study, and case studies. SETTING: University hospital. METHODS: Six soft cadavers were studied. The boundaries of the CTF and the needle pathway of CTF injection were identified in the first cadaver. The CTF and ESP injections were performed on either the left or right sides of the T4 vertebral level in cadavers 2 to 6. Fifteen milliliters of 0.2% methylene blue was injected in each block, and the spread of dye was assessed by anatomic dissection. We also report 2 case studies of CTF and ESP blocks. RESULTS: Cadaver studies of CTF injection demonstrate that with injection to the inferior aspect of the base of the transverse process, the dye mainly passes anteriorly through the CTF into the paravertebral space, with minimal track-back to the deep back muscles. Consistent sensory blockade was achieved in 2 case studies. With the ESP injection, the spread of dye was observed cephalocaudad to the fascia of the erector spinae muscle, with no dye spreading within the paravertebral space in all cadavers. LIMITATIONS: Prospective case series. CONCLUSIONS: CTF block was consistently associated with a mainly anterior spread of injectate into the paravertebral space that involved the thoracic spinal nerves, and minimal posterior spread of injectate to the deep back muscles. KEY WORDS: Thoracic vertebrae, rib cage, paraspinal muscle, nerve block, joints.

Paravertebral block: anatomy and relevant safety issues.

Paravertebral block, especially thoracic paravertebral block, is an effective regional anesthetic technique that can provide significant analgesia for numerous surgical procedures, including breast surgery, pulmonary surgery, and herniorrhaphy. The technique, although straightforward, is not devoid of potential adverse effects. Proper anatomic knowledge and adequate technique may help decrease the risk of these effects. In this brief discourse, we discuss the anatomy and technical aspects of paravertebral blocks and emphasize the importance of appropriate needle manipulation in order to minimize the risk of complications. We propose that, when using a landmark-based approach, limiting medial and lateral needle orientation and implementing caudal (rather than cephalad) needle redirection may provide an extra margin of safety when performing this technique. Likewise, recognizing a target that is not in close proximity to the neurovascular bundle when using ultrasound guidance may be beneficial.

Can Denosumab cure giant cell tumors of the spine? A case report and literature review.

BACKGROUND: Bone giant cell tumors, although benign, may be locally aggressive and cause severe morbidity; in some cases, they can also disseminate at distance and cause death. Denosumab has been approved to treat unresectable bone giant cell tumors or when surgery is likely to result in severe morbidity. Furthermore, its curative potential has been recently suggested. CASE: An 18-year-old girl presented with a spinal giant cell tumor at T9. Neo-adjuvant denosumab was administered for 9 months with great clinical and analytical tolerance. A posterior left T9 costo-transversectomy and vertebral body curettage was performed and the spine stabilized. Interestingly, histopathology examination of the surgical specimens found no evidence of tumoral cells. Denosumab was reinstated until completion of 12 months of treatment. CONCLUSION: Denosumab has an important but still limited role in the treatment of spinal giant cell tumors. Here, it resulted in complete histological resolution of the tumor, potentially widening its applicability from a strictly neo-adjuvant to a curative role.

Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis.

We investigated the effect of triptolide (TP) on spinal cord injury (SCI), and its underlying mechanism. Following the establishment of the SCI model using YFP H-line transgenic mice, TP was intraperitoneally injected at a dose of 0.2 mg/kg once daily for 7 days. Behavioral tests, Nissl staining, and hematoxylin-eosin staining were employed to assess motor function recovery and neuronal cell death. Western blot and immunofluorescence staining were used to assess autophagy-associated proteins (LC3B, p62, Beclin-1) and the apoptosis-associated proteins (Bcl-2, caspase-3, Bax). The TP-treated group showed improved motor functions, and reduced neuronal cell death. Also, significant upregulation of Bcl-2 and LC3B expressions, with the downregulation of p62, Bax and caspase-3 expressions were found in the TP-treated group. Additionally, phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1 and ERK2) was decreased in the TP-treated group. TP mediates its protective effect in SCI by promoting the autophagic pathway while inhibiting the MAPK/ERK1/2 signaling pathway. These results demonstrate the therapeutic potential of TP in SCI.

Comparison of Clinical Efficacy and Anatomical Investigation between Retrolaminar Block and Erector Spinae Plane Block.

Retrolaminar block (RLB) and erector spinae plane block (ESPB) are alternative approaches to paravertebral block (PVB) and are advantageous in that they are easier and safer techniques compared with the traditional PVB. Many clinical reports of these blocks have described their efficacy for ipsilateral thoracic analgesia. The local anesthetic injection points of RLB and ESPB are the lamina and transverse process, respectively. Despite the similarity of the puncture sites, there have been no clinical studies comparing RLB and ESPB. In addition, the underlying mechanism of these blocks has not been clarified. Recent anatomical investigations indicated that the injectate was distributed in the paravertebral space and spread laterally into the intercostal spaces. The limited distribution into the paravertebral space indicated that compared to PVB, RLB and ESPB exert their effects via a different mechanism. In this review, we describe the features of and differences between RLB and ESPB based on current clinical and anatomical reports. We also propose the clinical indication and discuss the differences, clinical outcomes, and anatomical mechanisms of the techniques.

Relief of refractory renal colic in emergency department: A novel indication for ultrasound guided erector spinae plane block.

Plane blocks have become very popular in recent years with the introduction of ultrasonography into the regional anesthesia and algology practice. Erector spinae plane (ESP) block involves injection of local anesthetics between erector spinae muscles and transverse process of vertebrae and can block the dorsal and ventral rami of thoracolumbar spinal nerves. The primary factor in the great popularity of this block is easy sonographic identification of landmarks and lower complication rate compared to paravertebral or central neuroaxial blocks. These characteristics mean that it will in all probability be widely used in the future, not just for anesthetists, but also for emergency physicians. Here we first report a novel indication for ESP block in emergency department; renal colic.

Thoracic epidural analgesia (TEA) versus patient-controlled analgesia (PCA) in laparoscopic colectomy: a systematic review and meta-analysis.

PURPOSE: A meta-analysis of RCTs was designed to provide an up-to-date comparison of thoracic epidural analgesia (TEA) and patient-controlled analgesia (PCA) in laparoscopic colectomy. METHODS: Our study was completed following the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic literature screening was performed in MEDLINE and Web of Science. Fixed effects (FE) or random effects (RE) models were estimated based on the Cochran Q test result. RESULTS: Totally, 8 studies were introduced in the present meta-analysis. Superiority of PCA in terms of length of hospital stay (LOS) (WMD 0.73, p = 0.004) and total complication rate (OR 1.57, p = 0.02) was found. TEA had a lower resting pain visual analogue scale (VAS) score at Day 1 (WMD - 2.23, p = 0.005) and Day 2 (WMD - 2.17, p = 0.01). TEA group had also a systematically lower walking VAS. Moreover, first bowel opened time (first defecation) (WMD - 0.88, p < 0.00001) was higher when PCA was applied. CONCLUSIONS: TEA was related to a lower first bowel opened time, walking, and resting pain levels at the first postoperative days. However, the overall complication rate and LOS were higher in the epidural analgesia group. Thus, for a safe conclusion to be drawn, further randomized controlled trials (RCTs) of a higher methodological and quality level are required.

Spontaneous spinal epidural hematoma of the thoracic spine after herbal medicine: a case report.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is an uncommon disease, but it can lead to acute cord compression with disabling consequences. Identifiable reasons for spontaneous hemorrhage are vascular malformations and bleeding disorders. However, SSEH after taking herbal medicines has not been described yet. CASE PRESENTATION: A 60-year-old female experienced sudden back pain combined with numbness and weakness in the lower limbs for several hours with no trauma, drug use, family history or any disease history. Her deep tendon reflexes were normoactive, and Babinski was negative. An emergent MRI showed a spinal epidural hematoma extending from T3 to T5. She was taken to surgery after immediate clinical and laboratory evaluations had been completed. Emergency decompression with laminectomy was performed and the patient recovered immediately after the surgery. Additional history taken from the patient at outpatient clinic after discharge revealed that she had been continuously taking herbal medicine containing black garlic for 8 weeks. CONCLUSION: To our knowledge, no report has been previously issued on SSEH after taking herbal medicines. Although contradictory evidence is present on bleeding risks with herbal uses, we believe that it's reasonable to ascertain if patients with SSEP are taking herbal medication before or during spinal surgery.

Cholinergic-mediated coordination of rhythmic sympathetic and motor activities in the newborn rat spinal cord.

Here, we investigated intrinsic spinal cord mechanisms underlying the physiological requirement for autonomic and somatic motor system coupling. Using an in vitro spinal cord preparation from newborn rat, we demonstrate that the specific activation of muscarinic cholinergic receptors (mAchRs) (with oxotremorine) triggers a slow burst rhythm in thoracic spinal segments, thereby revealing a rhythmogenic capability in this cord region. Whereas axial motoneurons (MNs) were rhythmically activated during both locomotor activity and oxotremorine-induced bursting, intermediolateral sympathetic preganglionic neurons (IML SPNs) exhibited rhythmicity solely in the presence of oxotremorine. This somato-sympathetic synaptic drive shared by MNs and IML SPNs could both merge with and modulate the locomotor synaptic drive produced by the lumbar motor networks. This study thus sheds new light on the coupling between somatic and sympathetic systems and suggests that an intraspinal network that may be conditionally activated under propriospinal cholinergic control constitutes at least part of the synchronizing mechanism.

Is a Retrolaminar Approach to the Thoracic Paravertebral Space Possible?: A Human Cadaveric Study.

BACKGROUND AND OBJECTIVES: The retrolaminar block (RB) is used for truncal analgesia, but its mechanism of neural blockade remains obscure. We sought to learn the pattern of local anesthetic spread after thoracic RB using cadaveric models. METHODS: In 8 fresh cadavers, an ultrasound-guided T4 RB was performed with 20 mL of methylene blue 1% and bupivacaine 0.5%. For comparison, an RB at T9 in 1 cadaver and a T4 thoracic paravertebral block in another cadaver were performed. Subsequently, posterior and anterior thoracic dissections were performed to examination where the dye spread. RESULTS: After T4 RB, dye was noted to spread in the ipsilateral retrolaminar plane (all 8 cadavers, median cephalad spread 3.5 cm, caudad spread 10.7 cm, lateral spread 2.5 cm), the contralateral retrolaminar plane (6 cadavers), the paravertebral space (5 cadavers, median of 3 segments, T3-T5), the intercostal space (5 cadavers, median of 3.5 cm laterally), the T4 epidural space (6 cadavers), and the intervertebral foramina (4 cadavers, median of 2 segments, T4-T5). After T9 retrolaminar injection, dye was noted in the ipsilateral retrolaminar plane (5.5 cm cephalad, 13.5 cm caudad, and 2.5 cm lateral), the contralateral retrolaminar plane, and the epidural space. Dye after T4 traditional paravertebral block spread to T1-T6 paravertebral space with 15-cm lateral spread. CONCLUSIONS: Injectate spread to the paravertebral space, epidural space, intercostal space, and intervertebral foramina is possible in the RB but is quite variable. In comparison to the thoracic paravertebral block, injectate spread within the paravertebral space is more limited.

A Cadaveric Study Investigating the Mechanism of Action of Erector Spinae Blockade.

BACKGROUND AND OBJECTIVES: Erector spinae block is an ultrasound-guided interfascial plane block first described in 2016. The objectives of this cadaveric dye injection and dissection study were to simulate an erector spinae block to determine if dye would spread anteriorly to the involve origins of the ventral and dorsal branches of the spinal nerves. METHODS: In 10 unembalmed human cadavers, 20 mL of 0.25% methylene blue dye was injected bilaterally into the plane between the fifth thoracic transverse process and erector spinae muscle. An in-plane ultrasound-guided technique with the transducer orientated longitudinally was used. During dissection, superficial and deep muscles were identified, and extent of dye spread was documented in cephalocaudal and lateral directions. The ventral and dorsal rami of spinal nerves and dorsal root ganglion at each level were examined to determine if they were stained by dye. RESULTS: There was extensive cephalocaudad and lateral spread of dye deep and superficial to the erector spinae muscles. Except for 1 injection (from 20), the ventral rami were not stained by the dye. In only 2 injections did the dye track posteriorly through the costotransverse foramen to the dorsal root ganglion. In all other cases, the dorsal root ganglia were not involved in the dye injection. The dye stained the dorsal rami posterior to the costotransverse foramen. CONCLUSIONS: There was no spread of dye anteriorly to the paravertebral space to involve origins of the ventral and dorsal branches of the thoracic spinal nerves. Dorsal ramus involvement was posterior to the costotransverse foramen.

Real-time view of anesthetic solution spread during an ultrasound-guided thoracic paravertebral block.

BACKGROUND: Thoracic paravertebral block is a technique for perioperative analgesia in patients undergoing thoracic, chest wall, or breast surgery, or for pain management with rib fractures, which can be performed with or without ultrasound guidance. The ultrasound guidance technique can be used to identify the thoracic paravertebral space, guide needle placement, monitor the spread of local anesthetic (LA) solution, and reduce complications such as pleural puncture and pneumothorax. The possibility of assessing anesthetic spread in real time using ultrasound guidance during paravertebral block offers numerous advantages, including the immediate and accurate identification of the extent of nervous block, with a consequent reduction of LA dose. The real-time visualization of spread may be used to achieve good anesthetic cover by administering the block at a single level, thus reducing complications normally associated with the technique. CASE SUMMARY: This case report describes the use of ultrasound-guided thoracic paravertebral block, at thoracic (T) 4 and 5 levels, in a patient undergoing breast surgery for perioperative analgesia. The authors were able to witness cranial diffusion of LA at T3-T4 in real time, and measure the increase in space between the costotransverse ligament and pleura, as an indication of anesthetic spread, at T2-T3 and T6-T7 levels. CONCLUSIONS: This is the first known case in the literature of direct viewing of LA diffusion in a paravertebral space other than the one in which the block is administered and may open important scenarios for the improvement of anesthesia technique.

Teriparatide treatment exerts differential effects on the central and peripheral skeleton: results from the MOAT study.

The central and peripheral skeleton was characterised using imaging techniques during 104 weeks of teriparatide treatment. Teriparatide exerts differential effects on the central and the peripheral skeleton. Overall, we did not observe a change in total body bone mineral. Our conclusions are constrained by the study limitations. INTRODUCTION: Teriparatide stimulates bone formation and resorption and therefore can cause bone gain and loss. We simultaneously characterised the central and peripheral skeleton using imaging techniques to better understand the mechanism of action of teriparatide. METHODS: Postmenopausal, osteoporotic women (n = 20, 65.4 ± 5.5 years) were recruited into a 104-week study of teriparatide. Imaging techniques included DXA, quantitative computed tomography (QCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Total lumbar spine areal bone mineral content (aBMC) (+ 11.2%), total lumbar spine areal bone mineral density (aBMD) (+ 8.1%), subregional thoracic spine aBMD (+ 7.5%), lumbar spine aBMC (+ 23.5%), lumbar spine aBMD (+ 11.9%), pelvis aBMC (+ 9.3%), and pelvis aBMD (+ 4.3%) increased. However, skull aBMC (- 5.0%), arms aBMC (- 5.1%), legs aBMC (- 2.9%), and legs aBMD (- 2.5%) decreased. Overall, we did not observe a change in total body bone mineral. Increases in L1-L3 volumetric BMD (vBMD) (+ 28.5%) occurred but there was no change in total proximal femur vBMD. Radius and tibia cortical vBMD (- 3.3 and - 3.4%) and tissue mineral density (- 3.2 and - 3.8%) decreased and there was an increase in porosity (+ 21.2 and + 10.3%). Tibia, but not radius, trabecular inhomogeneity (+ 3.2%), and failure load (+ 0.2%) increased, but cortical thickness (- 3.1%), area (- 2.9%), and pore volume (- 1.6%) decreased. CONCLUSIONS: Teriparatide exerts differential effects on the central and the peripheral skeleton. Central trabecular vBMD (L1-L3) is improved, but there is a concomitant decrease in peripheral cortical vBMD and an increase in porosity. Overall, we did not observe a change in total body bone mineral. We acknowledge that our conclusions may be speculative and are constrained by the technical limitations of the imaging techniques used, the lack of a control group, and the small sample size studied.

Bisphosphonate and Teriparatide Use in Thoracolumbar Spinal Fusion: A Systematic Review and Meta-analysis of Comparative Studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare the efficacy of the use of either bisphosphonates or teriparatide on radiographic and functional outcomes of patients that had thoracolumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Controversy exists as to whether bisphosphonates interfere with successful spinal arthrodesis. An alternative osteoporosis medication is teriparatide, a synthetic parathyroid hormone that has an anabolic effect on osteoblast function. To date, there is limited comparative data on the influence of bisphosphonates or teriparatide on spinal fusion. METHODS: A systematic search of medical reference databases was conducted for comparative studies on bisphosphonate or teriparatide use after thoracolumbar spinal fusion. Meta-analysis was performed using the random-effects model for heterogeneity. Radiographic outcomes assessed include fusion rates, risk of screw loosening, cage subsidence, and vertebral fracture. RESULTS: No statistically significant differences were noted between bisphosphonates and control groups regarding fusion rate and risk of screw loosening (fusion: odds ratio [OR] = 2.2, 95% confidence interval [CI]: 0.87-5.56, P = 0.09; loosening: OR = 0.45, 95% CI: 0.14-1.48, P = 0.19). Teriparatide use was associated with higher fusion rates than bisphosphonates (OR = 2.3, 95% CI: 1.55-3.42, P < 0.0001). However, no statistically significant difference was noted between teriparatide and bisphosphonates regarding risk of screw loosening (OR = 0.37, 95% CI: 0.12-1.18, P = 0.09). Lastly, bisphosphonate use was associated with decreased odds of cage subsidence and vertebral fractures compared to controls (subsidence: OR = 0.29, 95% CI 0.11-0.75, P = 0.01; fracture: OR = 0.18, 95% CI 0.07-0.48, P = 0.0007). CONCLUSION: Bisphosphonates do not appear to impair successful spinal fusion compared to controls although teriparatide use is associated with higher fusion rates than bisphosphonates. In addition, bisphosphonate use is associated with decreased odds of cage subsidence and vertebral fractures compared to controls that had spinal fusion. LEVEL OF EVIDENCE: 3.

The Effect of Ketorolac on Thoracolumbar Posterolateral Fusion: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: The purpose of this study was to evaluate the effect of postoperative ketorolac administration (ie, dosage and duration of use) on pseudarthrosis following thoracolumbar posterolateral spinal fusions. SUMMARY OF BACKGROUND DATA: Ketorolac is a nonsteroidal anti-inflammatory drug often administered for pain control after spine surgery. The main concern with ketorolac is the risk of pseudarthrosis following fusion. MATERIALS AND METHODS: A systematic search of multiple medical reference databases was conducted for studies detailing postoperative ketorolac use in lumbar fusion and scoliosis surgery in adult and pediatric patients, respectively. Meta-analysis was performed using the random-effects model for heterogeneity as this study analyzes heterogenous patient populations undergoing variable approaches to fusion and variable numbers of levels with variable means of detection of pseudarthrosis. Outcome measure was pseudarthrosis. RESULTS: Overall, 6 studies totaling 1558 patients were reviewed. Pseudarthrosis was observed in 119 (7.6%) patients. Pseudarthrosis were observed in adults with ketorolac administered for >2 days [odds ratio (OR), 3.44, 95% confidence interval (95% CI), 1.87-6.36; P<0.001], adults with doses of ≥120 mg/d (OR, 2.93, 95% CI, 1.06-8.12; P=0.039), and adults with ketorolac administered for >2 days and at doses ≥120 mg/d (OR, 4.75, 95% CI, 2.34-9.62; P<0.001). Ketorolac use in smokers was associated with pseudarthrosis (OR, 8.71, 95% CI, 2.23-34.0; P=0.002). CONCLUSION: Ketorolac, when administered for >2 days and/or at a dose of ≥120 mg/d, is associated with pseudarthrosis in adults after posterolateral lumbar fusion. Ketorolac use in smokers is also associated with pseudarthrosis.

Repairability of skeletal alterations induced by sodium valproate in rats.

The present study aimed at examining postnatal repairability of sodium valproate-induced skeletal alterations in rats. Sodium valproate (400 mg/kg) or the vehicle (distilled water) was orally administrated to pregnant Sprague-Dawley rats from gestation days 9 to 11. Fetuses and pups were obtained on gestation day 21 and postnatal day 11, respectively, and their skeletons were stained with Alizarin red S and Alcian blue and examined. Sodium valproate-induced costal and vertebral alterations in the fetuses included discontinued rib cartilage, fused rib, full or short supernumerary rib, bipart ossification of thoracic centrum, supernumerary lumbar vertebrae, and lumbarization. In pups, however, discontinued rib cartilage was not observed, and the incidence of a short supernumerary rib was significantly lower than that in the fetuses, suggesting that these alterations are postnatally repairable.

Effects of mTOR/NF-κB signaling pathway and high thoracic epidural anesthesia on myocardial ischemia-reperfusion injury via autophagy in rats.

We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size. TUNEL staining was adopted to detect the cell apoptosis rate. The mRNA and protein levels of mTOR, NF-κB, Fasl, Bcl-2 and Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western blotting, respectively. The findings indicated that compared with the normal and sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial infarction size and increased cell apoptosis rate, while the results in the HTEA + PDTC group were opposite. Compared with the normal and sham groups, the I/R group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65, Bax, and Fasl. These results prove that the inhibition of mTOR/NF-κB signaling pathway potentiates HTEA against myocardial IR injury by autophagy and apoptosis in rats.