Search

Three Shiba goats aged 1 to 7 years kept in Ibaraki prefecture in Japan were presented with chief complaint of lumbar paralysis or gait abnormalities. As cerebrospinal setariasis were suspected in all cases at the first stage, ivermectin was administered to treat, but the response was insufficient. Necropsy revealed abscess formation on the ventral side of the spine at T5 in Case 1, T5-6 in Case 2, and C7-T1 in Case 3, causing compression of the spinal cord in all three cases. In addition to cerebrospinal setariasis, vertebral abscess should be considered as a cause of paresis or gait abnormalities in goats in Japan. Computed tomography was a useful for diagnosing vertebral abscess.

Objectives: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies., Methods: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis was performed to evaluate the factors associated with yield., Results: A total of 570 biopsies performed on 527 patients were included. A histopathologic diagnosis of osteomyelitis was made in 68.4% (359 of 525) of biopsies, and microbiological cultures were positive in 29.6% (169 of 570). Elevated erythrocyte sedimentation rate was positively associated with a histopathologic diagnosis of osteomyelitis (odds ratio [OR] =1.96, P = 0.007) and positive cultures from bone cores (OR = 1.02, P ≤0.001) and aspirate (OR = 1.02, P ≤0.001). Increased total core length was positively associated with a histopathologic diagnosis of osteomyelitis (OR = 1.81, P = 0.013) and positive cultures from bone cores (OR = 1.65, P = 0.049). Clinical management was affected by ICNB in 37.5% (214 of 570) of cases., Conclusions: In this large cohort, ICNB yielded approximately 30% positive cultures and changed clinical management in over one-third of the patients., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Vertebral infections, including vertebral osteomyelitis, septic physitis, and discospondylitis, are rarely reported in goats, and when reported, have been largely limited to necropsy case reports., Objective: Describe clinical findings and outcome in goats with vertebral infections evaluated by computed tomography (CT)., Animals: Five goats with vertebral osteomyelitis, septic physitis, and discospondylitis evaluated by CT., Methods: Retrospective case series., Results: The most common presenting complaints were progressive weakness, paresis and recumbency. Three goats were tetraparetic and 2 goats had pelvic limb paraparesis. Clinicopathologic findings included leukocytosis, mature neutrophilia, and hyperfibrinogenemia. The most common vertebrae affected were C7-T1. All 5 goats had discospondylitis with or without vertebral osteomyelitis and septic physitis. Computed tomographic evidence of spinal cord compression was present in 4/5 goats. Medical management (antimicrobials, physical therapy, analgesia, supportive care) was attempted in 4 goats, and 1 goat was euthanized at the time of diagnosis. All 4 goats that were treated regained ambulatory ability and survived to hospital discharge., Conclusions and Clinical Importance: Despite severity of CT imaging findings, goats with discospondylitis, septic physitis, and vertebral osteomyelitis can successfully return to ambulatory function. Additional studies are required to determine ideal treatment regimens., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Spinal diseases often result in compromised mobility and diminished quality of life due to the intricate anatomy surrounding the nervous system. Medication and surgical interventions remain the primary treatment methods for spinal conditions. However, currently available medications have limited efficacy in treating spinal surgical diseases and cannot achieve a complete cure. Furthermore, surgical intervention frequently results in inevitable alterations and impairments to the initial anatomical integrity of the spinal structure, accompanied by the consequential loss of certain physiological functionalities. Changes in spine surgery treatment concepts and modalities in the last decade have led to a deepening of minimally invasive treatment, with treatment strategies focusing more on repairing and reconstructing the patient's spine and preserving physiological functions. Therefore, developing novel and more efficient treatment strategies to reduce spinal lesions and iatrogenic injuries is essential. In recent years, significant advancements in biomedical research have led to the discovery that hydrogels possess excellent biocompatibility, biodegradability, and adjustable mechanical properties. The application of hydrogel-based biotechnology in spinal surgery has demonstrated remarkable therapeutic potential. This review presents the therapeutic strategies for spinal diseases based on hydrogel tissue engineering technology.

Objective: Response of pyogenic spine infection to antibiotic therapy is usually based on nonspecific symptoms and inflammation markers. Abnormalities on MRI persist too long to influence therapy. Is FDG-PET/CT a timely and robust predictor of successful therapy?, Materials and Methods: Retrospective study. Sequential FDG-PET/CTs done to assess treatment response over a 4-year period. Recurrence of infection after stopping treatment was the endpoint., Results: One hundred seven patients enrolled. First treatment response scan showed no signs of infection in 69 patients (low risk). Twenty-four additional patients underwent additional treatment after an initial positive scan with low-risk pattern on follow-up imaging. After stopping antibiotics, none had clinical recurrence of infection. One had positive cultures at surgery for negative predictive value of 0.99. Thirty-eight patients had evidence of residual infection. Abnormalities in 28 were comparable to what is seen with untreated infection (high-risk). Twenty-seven received additional treatment until resolution. Antibiotics were stopped in 1 who suffered recurrence. Ten had low-grade/localized abnormalities consistent with infection (intermediate-risk). Signs of infection resolved in 3 after additional treatment. Of the remaining 7 patients who had minor residual abnormalities when antibiotics were stopped, 1 had recurrent infection for a positive predictive value of 0.14., Conclusion: Risk stratification proposed: A low-risk scan with only inflammation at a destroyed joint indicates negligible risk of recurrence. Unexplained activity in bone, soft tissue or spinal canal indicates high risk with further antibiotics recommended. Most patients with subtle or localized findings (intermediate risk) did not experience recurrence. Stopping therapy could be considered under careful observation., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

A meeting of Interdisciplinary Expert Panel with leading specialists in the field of orthopedics/traumatology, surgery, rheumatology, and neurology was held in Moscow on February 10, 2023. The purpose of the meeting was to discuss the current status of local injection therapy (LIT) in Russia and the rationale behind the use of collagen-based products for various musculoskeletal disorders. The experts considered the following issues: (1) General contraindications to the use of medical products based on tropocollagen as well as an algorithm for actions in case of adverse events; (2) Guidelines regarding LIT in general and LIT using tropocollagen in particular, including in combination with other LIT products; (3) Particular indications and approaches to the treatment of patients with abnormal changes in appendicular joints and spine with damage to both intra-articular structures and periarticular soft tissue.

Background: Handgrip strength (HGS) and psoas muscle index (PMI) are widely used protocols for screening or diagnosing sarcopenia by measuring muscle strength and mass. Epidural steroid injection (ESI) is a common intervention for the treatment of spinal pain; however, the influence of pre-procedural sarcopenic status on therapeutic effects after ESI has not been investigated., Objectives: In the present study, whether pre-procedural HGS or PMI predicts analgesic efficacy of ESI in elderly patients with degenerative lumbar spinal disease was investigated., Study Design: This was a retrospective observational study., Setting: The study included patients from the outpatient department for interventional pain management at a university hospital., Methods: Following institutional review board (IRB) approval, patients >= 65 years of age who underwent fluoroscopy-guided lumbar ESI from 2016 to 2017 in our clinic were enrolled in the present study. Good analgesia was defined as >= 50% reduction in pain score at 4 weeks after injection. Patient characteristics, pain-related factors, clinical factors, HGS, and PMI measurements were collected and analyzed using multivariate analysis to identify the predictors of good analgesia after lumbar ESI. In addition, a receiver operating characteristic curve (ROC) analysis was performed, and area under the curve (AUC) values with 95% confidence interval (CI) were calculated for the HGS., Results: A total of 259 patients satisfied the study protocol requirements. HGS was significantly higher in the good analgesia group (23.12 ± 7.54 vs 16.55 ± 6.66 kg, P < 0.001). However, the PMI did not differ between the 2 groups (5.25 ± 1.55 vs 5.08 ± 1.69 cm2/m2, P = 0.406). Multivariate analysis revealed higher HGS (odds ratio, OR = 1.142, 95% CI = 1.094-1.193, P < 0.001) and low-grade foraminal stenosis (OR = 0.403, 95% CI = 0.199-0.814, P = 0.011) were significantly associated with good analgesia after injection. The AUC values with 95% CI for HGS were 0.819 (0.718-0.920) in men and 0.800 (0.732-0.869) in women. In addition, HGS cutoff values for predicting good analgesic outcomes were 26.5 kg in men and 16.5 kg in women., Limitations: This study was conducted in a single center, and sample size was relatively small. The lack of physical performance evaluation did not fully meet the current criteria for sarcopenia. In addition, post-procedural clinical data associated with disability or quality of life could not be collected., Conclusion: In the present study, pre-procedural HGS was an independent predictor of analgesic efficacy after ESI in elderly patients with degenerative lumbar spinal disease. However, the PMI was not associated with pain relief after injection.

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used as an alternative bone graft in spine fusion surgery. However, clinical outcome such as effects and complications has not yet been revealed for transforaminal lumbar interbody fusion (TLIF). Although previous studies have reported some results, the evidence is weak. Therefore, the purpose of this trial is to evaluate the effectiveness and safety of Escherichia coli-derived rhBMP-2 combined with hydroxyapatite (HA) in TLIF., Methods: This trial is designed as a prospective, assessor-blinded, open-label, multicenter, randomized controlled study. Participants will be recruited from six tertiary teaching hospitals. All randomized participants will be undergoing one- or two-level TLIF with rhBMP-2 (77 participants) as the active experimental group or with an auto-iliac bone graft (77 participants) as the control group. The primary interbody fusion rate outcome will be evaluated using computed tomography (CT) 12 months after surgery. The secondary outcomes will be as follows: clinical outcomes (visual analog scale score, EuroQol-5-dimensions-5-level score, Oswestry Disability Index score, and some surgery-related variables) and adverse effects (radiculitis, heterotrophic ossification, endplate resorption, and osteolysis). Radiological outcomes will be evaluated using simple radiography or CT. All outcomes will be measured, collected, and evaluated before surgery and at 12, 24, and 52 weeks postoperatively., Discussion: This study will be the primary of its kind to evaluate the effectiveness and safety of E. coli-derived rhBMP-2 with HA in one- or two-level TLIF. It is designed to evaluate the equivalence of the results between rhBMP-2 with HA and auto-iliac bone graft using an appropriate sample size, assessor-blinded analyses, and prospective registration to avoid bias. This study will set up clear conclusions for using E. coli-derived rhBMP-2 with HA in TLIF., Trial Registration: This study protocol was registered at Korea Clinical Research Information Service ( https://cris.nih.go.kr ; number identifier: KCT0005610) on 19 November 2020. And protocol version is v1.1, January 2022., (© 2022. The Author(s).)

Background: Spondylodiscitis is a severe condition where standalone antibiotic therapy resolves most cases. In refractory infections, open surgery may aid with infection debulking. However, significant morbidity can occur. Nowadays, endoscopic approaches are emerging as an alternative. However, until now, only small-scale studies exist. Being so, we carried the first systematic review on spondylodiscitis endoscopic debridement indications, technique details, and outcomes., Methods: Search for all English written original studies approaching the spondylodiscitis endoscopic treatment was performed using PubMed and EBSCO host. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a pre-specified protocol was registered at PROSPERO (CRD42020183657)., Results: Fourteen studies involving 342 participants were included for analysis. Data overall quality was fair. Indications for the endoscopic approach were poorly defined. The most consensual indication was refractory infection to conservative treatment. Spinal instability or neurological deficits were common exclusion criteria. All authors described similar techniques, and despite the frequent severe co-morbidities, procedure morbidity was low. Re-interventions were common. Microorganism identification varied from 54.2 to 90.4%. Treatment failure among studies ranged from 0 to 33%. Pain, functional status, and neurological deficits had satisfactory improvement after procedures., Conclusions: The endoscopic debridement of spondylodiscitis seems to be an effective and safe approach for refractory spondylodiscitis. A novel approach with initial endoscopic infection debulking and antibiotic therapy could improve the success of spondylodiscitis treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Spinal fusion is the mainstay treatment for various spinal conditions ranging from lumbar and cervical stenosis to degenerative spondylolisthesis as well as extensive deformity corrections. A new emerging category of allograft is cellular bone matrices (CBMs), which take allogeneic mesenchymal stem cells and incorporate them into an osteoconductive and osteoinductive matrix. This study reviewed the current spinal fusion options and new emerging treatment options., Methods: Articles were searched using PubMed. The search included English publications since January 1, 2014, using the search terms "cellular bone matrix," "mesenchymal stem cells spinal fusion," "spinal arthrodesis AND mesenchymal stem cells," and "spine fusion AND cellular bone matrix.", Results: Spinal fusion is accomplished through the use of allografts, autografts, and bone graft substitutes in combination or alone. An emerging category of allograft is CBMs, in which an osteoconductive and osteoinductive matrix is filled with mesenchymal stem cells. Studies demonstrate that CBMs have achieved equivalent or better fusion rates compared with traditional options for anterior cervical discectomy and fusions and posterolateral lumbar fusions; however, the studies have been retrospective and lacking control groups and therefore not ideal., Conclusions: Many treatment options have been successfully used in spinal fusion. Newer allografts such as CBMs have shown promising results in both animal and clinical studies. Further research is needed to determine the therapeutic dose of mesenchymal stem cells delivered within CBMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: With the development of evidence-based guidelines for the diagnosis and antibiotic treatment of patients with pyogenic vertebral osteomyelitis, various nonsurgical and surgical treatment strategies have achieved favorable results. However, sufficient administration of appropriate antibiotics is a prerequisite for treatment success, which cannot be guaranteed in patients with culture-negative pyogenic vertebral osteomyelitis. Unfortunately, previous studies on culture-negative pyogenic vertebral osteomyelitis were limited by small patient groups, short follow-up periods, varied treatment protocols, and inconsistently defined clinical endpoints., Questions/purposes: Among patients treated according to our center's treatment protocol for culture-negative pyogenic vertebral osteomyelitis, which included patients treated without surgery, with surgery but without spinal instrumentation, as well as patients treated with instrumented surgery, (1) what proportion of patients in each treatment group experienced recurrence (or persistence) of infection, complications of treatment, and death; and (2) what factors were independently associated with recurrent or persistent infection after treatment under this algorithm?, Methods: This was a retrospective evaluation of a treatment protocol in use at one center from 2008 to 2020. During that time, we treated 183 patients for culture-negative pyogenic vertebral osteomyelitis. The diagnosis was based on clinical, laboratory, and radiological features excluding disease that presents similar features to pyogenic vertebral osteomyelitis. For those patients, our protocol included three possible approaches: nonsurgical treatment, including the use of empirical antibiotics (nonoperative group, n = 82); spinal decompression without instrumentation (noninstrumented group, n = 41); and spinal decompression with instrumentation (instrumented group, n = 60). The indications for each treatment during the period remained relatively consistent. Nonsurgical treatment including empirical antibiotics was applied to all patients according to the specified antibiotic protocol. Spinal decompression without instrumentation was employed when a patient presented substantial or aggravating neurologic deficits or intractable pain from an abscess. Instrumentation was added in patients with mechanical instability before or after spinal decompression. Minimum follow-up to be included in this study was 1 year, and 91% (252 of 277) of patients were accounted for at that time, with no differential loss to follow-up among the study groups (12, five, and four patients missing from the three groups, respectively, at 1 year). Chart review was performed to ascertain the proportion of patients in each group who experienced recurrence, complications, and death. Factors associated with recurrence were assessed across the entire cohort using a multivariable logistic model. We analyzed 1-year recurrence and mortality rates using the Kaplan-Meier method, and their 95% confidence intervals were calculated using the method by Hosmer and Lemeshow., Results: At 1 year, the recurrence-free survival rate was 87% (95% confidence interval 78% to 93%) in the nonoperative group, 87% (95% CI 72% to 94%) in the noninstrumented group, and 91% (95% CI 80% to 96%) in the instrumented group. The proportion of patients who experienced a major medical complication in each group was 12% (10 of 82), 10% (4 of 41), and 8% (5 of 60), respectively. At 1 year, the survival rate with patient death as the endpoint was 95% (95% CI 88% to 98%) in the nonoperative group, 95% (95% CI 82% to 99%) in the noninstrumented group, and 97% (95% CI 87% to 99%) in the instrumented group. After controlling for potentially confounding variables including age, medical comorbidities, and anatomical involvement of infection, the following factors were independently associated with increased odds of infection recurrence or persistence: higher Charlson Comorbidity Index (CCI) score (odds ratio 1.6 per point on the CCI [95% CI 1.2 to 2.1]; p = 0.004) and the presence of a psoas abscess (OR 4.7 [95% CI 1.6 to 13.9]; p = 0.005)., Conclusion: Among patients with negative initial nonoperative culture results, spinal decompression and abscess drainage can be used in those with substantial or aggravating neurological deficits or intractable pain caused by an abscess, while additional early spinal instrumentation can be applied upon consideration of their medical comorbidities and the presence of a psoas abscess when mechanical instability is present before or after the spinal decompression. Reasonable clinical results can be expected, regardless of the results from subsequent operative cultures. However, our study results should be replicated by other centers, and further studies that consider individual differences such as bone mineral density and include patients with previous spinal instrumentation or recurrent infection should be performed to establish a more comprehensive treatment protocol., Level of Evidence: Level IV, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

Objective: Bone morphogenetic protein (BMP) is a growth factor that aids in osteoinduction and promotes bone fusion. There is a lack of literature regarding recombinant human BMP-2 (rhBMP-2) dosage in different spine surgeries. This study aims to investigate the trends in rhBMP-2 dosage and the associated complications in spinal arthrodesis., Methods: A retrospective study was conducted investigating spinal arthrodesis using rhBMP-2. Variables including age, procedure type, rhBMP-2 size, complications, and postoperative imaging were collected. Cases were grouped into the following surgical procedures: anterior lumbar interbody fusion/extreme lateral interbody fusion (ALIF/XLIF), posterior lumbar interbody fusion/transforaminal lumbar interbody fusion (PLIF/TLIF), posterolateral fusion (PLF), anterior cervical discectomy and fusion (ACDF), and posterior cervical fusion (PCF)., Results: A total of 1209 patients who received rhBMP-2 from 2006 to 2020 were studied. Of these, 230 were categorized as ALIF/XLIF, 336 as PLIF/TLIF, 243 as PLF, 203 as ACDF, and 197 as PCF. PCF (P < 0.001), PLIF/TLIF (P < 0.001), and PLF (P < 0.001) demonstrated a significant decrease in the rhBMP-2 dose used per level, with major transitions seen in 2018, 2011, and 2013, respectively. In our sample, 129 complications following spinal arthrodesis were noted. A significant relation between rhBMP-2 size and complication rates (χ 2 = 73.73, P = 0.0029) was noted. rhBMP-2 dosage per level was a predictor of complication following spinal arthrodesis (odds ratio = 1.302 [1.05-1.55], P < 0.001)., Conclusions: BMP is an effective compound in fusing adjacent spine segments. However, it carries some regional complications. We demonstrate a decreasing trend in the dose/vertebral level. A decrease rhBMP-2 dose per level correlated with a decrease in complication rates., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

Abstract: Syphilitic spinal disease is a rare condition caused by the spirochete Treponema pallidum, either from direct spirochete involvement of the cord or as a consequence of indirect spirochete involvement of the meninges, blood vessels, or the vertebral column. After the introduction of penicillin therapy in the 1940s, it has become an increasingly rare condition. We report 3 challenging cases of syphilitic spinal disease presenting as myelopathy-1 with an extra-axial gumma of tertiary syphilis causing cord compression and 2 with tabes dorsalis complicated by tabetic spinal neuroarthropathy-each presenting a diagnostic dilemma to their treating physicians. We also review the literature for updates on modern investigative modalities and discuss pitfalls physicians need to avoid to arrive at the diagnosis., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare that they have no competing interests. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Aneurysmal bone cysts (ABCs) are rare benign pseudotumoral bone lesions with potential aggressive behavior due to the extensive destruction of surrounding bone. Traditionally, these tumors were treated with open surgery, but there is more and more a shift to less invasive procedures. In particular, treatment for spinal ABCs is generally unsatisfactory due to the risk of morbidity, neurological impairment and recurrence, and there is a need for innovative therapies. Denosumab has been reported as a useful treatment in giant cell tumors of bone (GCTB), so its efficacy has been tested also in other fibro-osseus lesions affecting children and adolescents, such as spinal aneurysmal bone cysts. The pediatric literature is limited to case reports and small series, all of which highlight the efficacy of this treatment on lesions growth and associated bone pain. Some of these reports have already reported well known side effects associated with denosumab, such as hypocalcemia at the beginning of the treatment, and rebound hypercalcemia at the discontinuation. The latter seems to be more frequent in children and adolescents than in adults, probably due to the higher baseline bone turnover in children. In addition, the use of denosumab in young patients could affect both bone modeling and remodeling, even if the consequences on the growing skeleton have not been reported in detail. Here we describe the case of a spinal ABC diagnosed in an 8-year old young boy which was not accessible to surgery but responded favorably to denosumab. Our aim is to describe the rapid changes in mineral and bone homeostasis in this patient, that required advice from the experts of the European Reference Network (ERN) for rare bone and endocrine diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Del Sindaco, Berlanga, Brugières, Thebault, Mantovani, Wicart and Linglart.)

Background/aim: This study’s aim was to investigate the effects of thymoquinone, which is the essential bioactive component of the volatile oil of Nigella sativa on the peridural fibrosis in rats following laminectomy., Materials and Methods: Twenty female Wistar Albino rats were used in our study. The rats were randomly divided into 2 groups: Sham and Surgery + Thymoquinone. Both groups underwent laminectomy at L1 under general anesthesia. The Sham group was not subjected to any drug application. The 2nd group was treated with intraperitoneal 10-mg/kg thymoquinone once per day for a period of 28 days, following the same surgical procedure. All of the group specimens were sacrificed after 4 weeks, and the laminectomy area was examined in terms of new bone volume, capillary volume, and fibrosis volume using stereological approaches., Results: Statistically significant differences were found between the Sham and Surgery + Thymoquinone groups in terms of new bone volume (P = 0.01), capillary volume (P = 0.01), and fibrosis volume (P < 0.001). It was noted that Thymoquinone caused a significant increase in new bone volume, vascular volume and, a significant decrease in fibrosis volume., Conclusion: The results of our study indicate that thymoquinone is effective in decreasing peridural fibrosis when applied to a laminectomy model., Competing Interests: The authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management., Methods: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis., Results: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups., Conclusions: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: Limited information is available about the proportion of patients with degenerative lumbar spinal disease (DLSD) who have gastrointestinal (GI) and cardiovascular (CV) risk factors. Many DLSD patients are prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) that are known to carry risks to the GI and CV systems by increasing GI bleeding and thromboembolic events. This study aimed to measure the prevalence of GI and CV risk in patients with DLSD and to ascertain whether the prescription of NSAIDs is in line with current guidelines., Methods: This study included 153 patients with symptomatic DLSD who were planning to undergo lumbar spinal surgery. The GI profile was checked using the GI Standardized Calculator of Risk for Event system and CV risk was evaluated using the presence of metabolic syndrome. The conformity of the prescription of NSAIDs was investigated according to the recommendations in current guidelines., Results: More than half of the patients (59.5%) had high or very high GI risk, and 66% of the patients were diagnosed with metabolic syndrome, which corresponds with CV risk. The rate of simultaneous GI and CV risk was 40.5% (n = 62 / 153; gastrointestinal Standardized Calculator of Risk for Event, > high and metabolic syndrome, yes). The actual prescription of NSAIDs was not in accordance with current guidelines., Conclusions: Two out of 3 patients had GI or CV risk factors, and approximately 40% of patients had both. Detailed assessment of GI and CV risk in patients with DLSD by using effective evaluation tools is mandatory for optimal medical treatment., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 by The Korean Orthopaedic Association.)

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., Competing Interests: The authors have declared that no competing interests exist.

There has been a surging interest in using elastomeric infusion devices to deliver outpatient parenteral antimicrobial therapy (OPAT), which is more cost-effective than standard antibiotic administration, which requires multiple daily home visits. This has been particularly important since the outbreak of the coronavirus pandemic, because reducing patient contact can also help to minimise transmission of COVID-19 to outpatients who are at a high risk of COVID-19-triggered complications. In this retrospective study, the clinical effectiveness of intravenous (IV) infusion of flucloxacillin using an elastomeric device was explored in a convenience sample of patients. Patients with three primary infective diagnoses-bloodstream infection, non-vertebral osteomyelitis and vertebral osteomyelitis-were included in the analyses. In non-vertebral osteomyelitis patients, Accufuser antibiotic infusion shortened the course of OPAT care relative to standard antibiotic administration (p<.05). In contrast, in vertebral osteomyelitis patients, it prolonged the course of OPAT care relative to standard administration (p<.05). In patients with bloodstream infections, no significant difference was found between the treatment modes (p=.93). Thus, the clinical effectiveness of Accufuser antibiotic infusion varies among patients with different infective diagnoses, and there seems to be a complex relationship between the method of antibiotic delivery and the patient's condition.

Background: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown., Objectives: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI., Study Design: A double-blind, parallel-group, randomized controlled trial., Setting: Pain clinics in a university hospital., Methods: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used., Results: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P < 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction., Limitations: There were selection bias and no placebo control., Conclusions: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids.

Study Design: Longitudinal Cohort Study OBJECTIVE.: The aim of this study was to determine whether duration of postoperative opioids is associated with long-term outcomes, and if initial postoperative opioid dosage is associated with opioid cessation after spine surgery., Summary of Background Data: Preoperative opioid use is associated with poor outcomes, but little evidence exists regarding the implications of opioid dosage and duration after spine surgery., Methods: Data from our state's prescription drug database was linked to our prospective clinical spine registry to analyze opioid dispensing and outcomes in elective surgical spine patients between 2010 and 2017. Patients were stratified based on preoperative chronic opioid use and multivariable regression was used to assess associations between duration of postoperative opioids and outcomes at one year, including satisfaction, chronic opioid use, and meaningful improvements in pain, disability, and quality of life. In a secondary aim, a Cox proportional hazards model was used to determine whether initial postoperative opioid dosage was associated with time to opioid cessation., Results: Of 2172 patients included, 35% had preoperative chronic opioid use. In patients without preoperative chronic opioid use, a postoperative opioid duration of 31 to 60 days was associated with chronic opioid use at 1 year (adjusted odds ratio [aOR]: 4.1 [1.7-9.8]) and no meaningful improvement in extremity pain (aOR: 1.8 [1.3-2.6]) or axial pain (aOR: 1.6 [1.1-2.2]); cessation between 61 and 90 days was associated with no meaningful improvement in disability (aOR: 2 [1.3-3]) and dissatisfaction (aOR:1.8 [1-3.1]). In patients with preoperative chronic opioid use, postoperative opioids for ≥90 days was associated with dissatisfaction. Cox regression analyses showed lower initial postoperative opioid dosages were associated with faster opioid cessation in both groups., Conclusion: Our results suggest that a shorter duration of postoperative opioids may result in improved 1-year patient-reported outcomes, and that lower postoperative opioid dosages may lead to faster opioid cessation., Level of Evidence: 2.

Background: Prescription opioid use and opioid-related deaths have become an epidemic in the United States, leading to devastating economic and health ramifications. Opioids are the most commonly prescribed drug class to treat low back pain, despite the limited body of evidence supporting their efficacy. Furthermore, preoperative opioid use prior to spine surgery has been reported to range from 20% to over 70%, with nearly 20% of this population being opioid dependent., Objective: To review the medical literature on the effect of preoperative opioid use in outcomes in spine surgery., Methods: We reviewed manuscripts published prior to February 1, 2019, exploring the effect of preoperative opioid use on outcomes in spine surgery. We identified 45 articles that analyzed independently the effect of preoperative opioid use on outcomes (n = 32 lumbar surgery, n = 19 cervical surgery, n = 7 spinal deformity, n = 5 "other")., Results: Preoperative opioid use is overwhelmingly associated with negative surgical and functional outcomes, including postoperative opioid use, hospitalization duration, healthcare costs, risk of surgical revision, and several other negative outcomes., Conclusion: There is an urgent and unmet need to find and apply extensive perioperative solutions to combat opioid use, particularly in patients undergoing spine surgery. Further investigations are necessary to determine the optimal method to treat such patients and to develop opioid-combative strategies in patients undergoing spine surgery., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Study Design: Prospective cohort study., Objective: To analyze the serum and drain concentrations of antibiotics administered by two different routes and compare the results., Summary of Background Data: Systemic antibiotics are expected to reach the surgical site and maintain adequate concentrations of the drug to prevent infection. However, it is unknown whether systemically administered antibiotics reach and maintain such adequate concentrations at the surgical wound or not., Methods: Forty patients undergoing elective spine surgery received intra-wound Vancomycin (1 GM) before the wound closure and single dose of intravenous Gentamycin (80MG) immediately after surgery. Blood and drain samples were collected postoperatively to estimate serum and drain concentrations of Gentamycin and Vancomycin. Drug Estimation Protocol: Drug concentrations were estimated by ADVIA Centaur CP immunoassay (direct chemiluminescence). Gentamycin and vancomycin in the test samples competes with their respective acridinium ester-labeled gentamicin and vancomycin derivatives for monoclonal mouse anti-gentamycin and anti-vancomycin antibodies which are covalently coupled to paramagnetic particles in the solid phase., Results: Gentamycin attained peak serum levels at 6 hours following administration with an average value of 9.90 ± 3.1 μg/mL which was decreased to 6.76 ± 2.6 μg/mL at 12 hours and steadily declining thereafter. Even though, the drug concentrations in the drain collection from the wound also attained peak levels at 6 hours, the drug concentrations were lower (3.75 ± 1.4 μg/mL) than that of serum concentrations and inadequately attained the recommended target peak of Gentamycin (4-12 μg/mL).Wound levels of local vancomycin were significantly higher at 6 hours (413.4 ± 217.3 μg/mL) and well maintained even at 72 hours. Serum vancomycin levels were observed to be highest at 6 hours in negligible concentrations of 6.06 ± 2.2 μg/mL., Conclusion: After prophylactic systemic administration of the antibiotics, the antibiotic drug concentrations in the wound are much lower than the serum concentrations at any given time. After local intra-wound application of antibiotics, the drug concentrations in the wound are well maintained even after 72 hours., Level of Evidence: 3.

Background: There are several open scientific questions regarding the optimal antibiotic treatment of spinal infections (SIs) with or without an implant. The duration of postsurgical antibiotic therapy is debated., Methods: We will perform two unblinded randomized controlled trials (RCTs). We hypothesize that shorter durations of systemic antibiotic therapy after surgery for SI are noninferior (10% margin, 80% power, α = 5%) to existing (long) treatment durations. The RCTs allocate the participants to two arms of 2 × 59 episodes each: 3 vs. 6 weeks of targeted postsurgical systemic antibiotic therapy for implant-free SIs or 6 vs. 12 weeks for implant-related SIs. This equals a total of 236 adult SI episodes (randomization scheme 1:1) with a minimal follow-up of 12 months. All participants receive concomitant multidisciplinary surgical, re-educational, internist, and infectious disease care. We will perform three interim analyses that are evaluated, in a blinded analysis, by an independent study data monitoring committee. Besides the primary outcome of remission, we will also assess adverse events of antibiotic therapy, changes of the patient's nutritional status, the influence of immune suppression, total costs, functional scores, and the timely evolution of the (surgical) wounds. We define infection as the presence of local signs of inflammation (pus, wound discharge, calor, and rubor) together with microbiological evidence of the same pathogen(s) in at least two intraoperative samples, and we define remission as the absence of clinical, laboratory, and/or radiological evidence of (former or new) infection., Discussion: Provided that there is adequate surgical debridement, both RCTs will potentially enable prescription of less antibiotics during the therapy of SI, with potentially less adverse events and reduced overall costs., Trial Registration: ClinicalTrials.gov, NCT04048304. Registered on 5 August 2019., Protocol Version: 2, 5 July 2019.

Background: Pseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels., Case Presentation: A 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek's and Trousseau's signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7-4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response., Conclusion: Pseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.

Background: The trajectory pattern of erythrocyte sedimentation rate (ESR) in patients with pyogenic vertebral osteomyelitis (PVO) and its clinical significance is unclear. We further evaluated whether the first-4-week ESR variability can predict the trajectory pattern, treatment duration and recurrence of PVO., Methods: The longitudinal ESR patterns of adults with PVO within the first 6 months were characterized through group-based trajectory modeling (GBTM). The ESR variability within the first 4 weeks was defined using the absolute difference (AD), coefficient of variation, percent change, and slope change. The first-4-week ESR variabilities were analyzed using ordinal logistic regression to predict the 6-month ESR trajectory and using logistic regression to predict treatment duration and recurrence likelihood. The discrimination and calibration of the prediction models were evaluated., Results: Three ESR trajectory patterns were identified though GBTM among patients with PVO: Group 1, initial moderate high ESR with fast response; Group 2, initial high ESR with fast response; Group 3, initial high ESR with slow response. Group 3 patients (initial high ESR with slow response) were older, received longer antibiotic treatment, and had more comorbidities and higher recurrence rates than patients in the other two groups. The initial ESR value and ESR - AD could predict the 6-month ESR trajectory. By incorporating the first-4-week ESR variabilities and the clinical features of patients, our models exhibited moderate discrimination performance to predict prolonged treatment (≥12 weeks; C statistic, 0.75; 95% confidence interval [CI], 0.70 to 0.81) and recurrence (C statistic, 0.69; 95% CI, 0.61 to 0.78)., Conclusions: The initial ESR value and first-4-week ESR variability are useful markers to predict the treatment duration and recurrence of PVO. Future studies should validate our findings in other populations., Competing Interests: The authors have declared that no competing interests exist.

We report a case of a 41-year-old male who presented to our institution with a large groin mass. CT, MRI and PET imaging was performed and was concerning for a soft tissue abscess likely originating in the lumbar spine. Differential considerations included infection, with atypical infections such as tuberculosis strongly considered. Biopsy revealed fungal elements preliminarily reported as consistent with Cryptococcus neoformans but later revealed to be Blastomyces dermatitidis. The patient responded positively following the introduction of appropriate treatment. This case illustrates the imaging similarities between spinal blastomycosis, spinal tuberculosis, and other fungal infections as well as the need for biopsy to differentiate.

Objective: Understanding the clinical and economic impact of opioid-related adverse drug events (ORADEs) within spine surgery may guide both the clinician's and hospital administration's approach to treating perioperative pain, thus improving patient care and reducing hospital costs. The objective of this analysis is to understand how potential ORADEs after spine surgery in elderly patients affect length of stay, hospital revenue and their association with comorbid conditions., Patients and Methods: We conducted a retrospective study utilizing the Center for Medicare/Medicaid Services Administrative Database to analyze Medicare discharges between April 2016 and March 2017 involving 14 spine surgery DRGs for major spine procedures in order to identify potential ORADEs. An analysis was conducted using this database to identify the incidence of potential ORADEs as well as their impact on mean hospital length of stay and hospital revenue., Results: There were 177,432 discharges during the study period. The ORADE rate in patients undergoing spine surgery was 13.9% (24,642/177,432). The mean length of stay (LOS) for discharges with an ORADE was 3.13 days longer than without an ORADE (6.29 days with an ORADE vs 3.16 days without an ORADE). The adverse post-operative outcomes most strongly associated with potential ORADEs included shock, pneumonia, and septicemia. The mean hospital revenue per day with an ORADE was $3,076 less than without an ORADE ($7,263 with an ORADE vs $10,339 without an ORADE)., Conclusion: Potential ORADEs in spine surgery in elderly patients are common and are associated with longer hospitalizations and decreased hospital revenue. Perioperative pain management strategies that reduce ORADEs may improve patient care and increase hospital revenue., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background Context: Data regarding risk of failure of nonoperative management in spinal epidural abscess (SEA) are limited. Given the potential for deterioration with treatment failure, a tool that predicts the probability of failure would be of great clinical utility., Purpose: We primarily aim to build a machine learning model using independent predictors of nonoperative management failure. Secondarily, we aim to develop an open-access web-based application that provides a patient-specific probability of treatment failure., Study Design/setting: Retrospective, case-control study., Patient Sample: Patients 18 years or older diagnosed with SEA at 2 academic medical centers and 3 community hospitals., Outcome Measures: Failure of nonoperative management., Methods: This is a retrospective cohort study of 367 patients with SEA initially managed nonoperatively between 1993 and 2016. The primary outcome was failure of nonoperative management defined as neurologic deterioration, worsened back and/or radicular pain, or persistent symptoms despite initiation of antibiotic therapy. Five machine learning algorithms were developed and assessed by discrimination, calibration, and overall performance., Results: Ninety-nine (27%) patients failed nonoperative management. Factors determined for prediction of nonoperative management were: motor deficit, diabetes, ventral component of abscess relative to thecal sac, history of compression or pathologic vertebral fracture, sensory deficit, active malignancy, and involvement of 3 or more vertebral levels. The elastic-net penalized logistic regression model was chosen as the final model given its superior discrimination, calibration, and overall model performance. This model was incorporated into an open access web application., Conclusion: By building a discriminative and well-calibrated model in a user-friendly and open-access digital interface, we hope to provide a prognostic tool that can be used to inform clinical decision-making in real-time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Context: Recently, preclinical and clinical studies suggest an association between renin-angiotensin system (RAS) blockers and bone healing, particularly in the context of osteoporotic bone fractures., Purpose: To determine the correlation between the use of RAS inhibitors and fusion outcomes and neurologic status in anterior cervical discectomy and fusion (ACDF) surgery., Study Design: Retrospective observational study., Patient Sample: Patients who underwent ACDF for degenerative disorders., Outcome Measures: Spinal fusion status and neurologic function (modified Japanese Orthopedic Association [mJOA] and Nurick grading scales)., Methods: A retrospective chart review was performed, including 200 patients who underwent ACDF for degenerative disorders with 1-year minimum follow-up. Demographic data, comorbidities, antihypertensive medication, neurologic examination, and fusion status were collected. Spinal fusion was assessed via plain cervical x-ray, resorting to dynamic radiographs and/or computer tomography (CT) in cases of uncertainty. Preoperative mJOA and Nurick scores and recovery rates were calculated to determine neurologic status., Results: Of the 200 patients (42.5% females, 57.5% males, median age of 53.7 years), 82 hypertensive patients were identified. Seventy-seven (93.9%) were taking antihypertensive medication as follows: 36.4% angiotensin-II receptor blockers (ARBs), 35.1% angiotensin-converting enzyme inhibitors (ACEIs), and the remaining patients were taking other medication. In the analysis of fusion rates, patients treated with ARBs exhibited a higher fusion rate, while those treated with ACEIs displayed a lower fusion rate compared to untreated nonhypertensive patients (p = .04 and .02, respectively). The difference in fusion rates between ARBs and ACEIs was also significant, with the former displaying higher rates (p < .001). Smoking exhibited a negative correlation with spinal fusion (p < .001). In the multivariate analysis, ARBs remained an independent factor for successful fusion (p = .02), while smoking remained a risk factor for failed fusion (p = .002). In the neurologic examination, ACEIs, hypertension status, and older age correlated with lower modified Japanese Orthopedic Association (mJOA) recovery rates (p = .001, <.001, and <.001, respectively) in the univariate analysis., Conclusions: In ACDF patients, we observed that ARBs were associated with higher fusion rates. Conversely, ACEIs and smoking were related to failed fusion. Prospective case-control studies are needed to confirm these RAS inhibitors effects on spinal fusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to review a case comprised of a cervical spinal epidural abscess, cervical and thoracic paraspinous edema, and widening of the right thoracic neural foramen secondary to a phlegmon., Methods: We reviewed the case of a spinal epidural abscess managed medically in a 4-year-old male and performed a review of the literature with 15 other cases that have previously been reported., Results: The current mainstay of treatment is largely variant but generally falls into a laminectomy-based surgical approach or longstanding antibiotics. Our review of the literature concluded that there are currently no clear guidelines established to recommend treatment, and current practice is largely based on the discretion of the pediatric neurosurgeon., Conclusions: Based on the literature review, and our personal case illustration, we conclude that an antibiotic-based treatment is a valid approach for therapy if initiated promptly in a pediatric patient with no neurological deficit.

Case: This report describes a 7-year-old girl with Langerhans cell histiocytosis (LCH) of the thoracic spine who developed neurological deterioration during nonsurgical management. She was treated with decompression and instrumented fusion followed by chemotherapy, recovered completely after surgery, and was doing well at 6-year follow-up., Conclusions: The best treatment of LCH of the spine is not clear, but in the setting of neurologic compromise after failing conservative management, surgical decompression with adjuvant chemotherapy should be considered.

Background: Spinal diseases are self-limited or non-progressive in many cases. Epidural steroid injection (ESI) is a common nonsurgical treatment option for spinal pain. Despite concerns about complications of repeated steroid injection, few studies reported on the adrenal function of spine disease patients undergoing surgery after ESI. We investigated the influence of preoperative multiple ESIs on adrenal function in spine surgery patients., Methods: This was a retrospective study with prospective data collection. Those who underwent elective spinal operations and had a history of multiple ESIs from January to June 2017 were selected as a study group. Those who underwent knee arthroplasty and did not have a history of ESI and any kind of steroid injection in other areas during 6 months before surgery were selected as a control group. Demographic data were compared to assess homogeneity between groups. We assessed the preoperative serum cortisol level (SCL) to compare the basal adrenal function between groups. Also, we assessed the elevation of SCL postoperatively to evaluate the adrenal response to the surgical stress in each group. For subgroup analysis, we divided all patients into normal (7-28 µg/dL) and subnormal groups according to SCL and analyzed risk factors of adrenal suppression with multivariate logistic regression test., Results: There were 53 patients in the study group and 130 in the control group. Age and sex were homogeneous between groups. There was significant intergroup difference in preoperative SCL (10.4 ± 4.8 µg/dL in the study group vs. 12.0 ± 4.2 µg/dL in the control group; p = 0.026).The postoperative day one SCL was 11.6 ± 5.0 µg/dL in the study group without significant increase from the preoperative level ( p = 0.117), whereas the increase was significant in the control group with a postoperative level of 14.4 ± 4.4 µg/dL ( p < 0.001). Among all patients, the SCL was subnormal in 18 patients and within the normal range in 165. Spine surgery was the independent risk factor irrespective of age and sex (odds ratio, 3.472; p = 0.015)., Conclusions: Our results suggest that concern should be raised about the influence of preoperative multiple ESIs on adrenal suppression in spine surgery patients., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: We have noted an increased number of cases of vertebral osteomyelitis secondary to Candida species over the past few years at our facility. Our aim was to identify and review these cases to elucidate risk factors, treatment regimens and outcomes., Methods: We performed a retrospective chart review using our electronic medical record and microbiology laboratory database to identify cases of vertebral osteomyelitis due to Candida at a single teaching hospital from 2006-2018., Results: We found 15 cases of Candida vertebral osteomyelitis. The majority of cases were due to Candida albicans and affected either the lumbar or the thoracic spine. Injection drug use and previous spine surgery were the two most common risk factors identified. Treatment was largely with intravenous antifungal induction followed by prolonged therapy with oral fluconazole. There was no short-term mortality though we lacked long-term follow-up on most patients., Conclusions: The number of vertebral infections due to Candida may be increasing. This may be partially driven by both a rise in intravenous drug use as well as the growing rate of spine surgery. Management following currently available guidelines seems favorable, though further studies are necessary to determine the optimal treatment regimen.

Competing Interests: Competing interests: None declared.

Background: Opioid use and misuse are urgent health issues. Previous studies suggest that opioid use increases healthcare resource use but severity adjustment is lacking., Objective: The objective of this study was to evaluate the severity-adjusted cost difference between opioid users and non-users among patients with conservatively managed degenerative joint disease of the spine within a large commercial health plan population in the United States., Methods: A retrospective observational study was performed using a national commercial database covering 531,819 patients aged 18-64 years with non-surgically managed cervical or lumbar degenerative spine disease during 2015-6. Patients were grouped based on whether there was evidence for an opioid prescription. Costs for the opioids themselves were excluded. Severity adjustment, on an ascending integer scale from 1 to 4, was performed based on member demographics, clinical comorbidities, disease progression indicators, and complications., Results: Median episode costs for patients given opioids were approximately twice that for patients not given opioids after severity adjustment. For patients with episodes in both years and stable severity, patients with new prescriptions for opioids in 2016 doubled their median 2015 costs, and patients who had opioids discontinued in 2016 had a 60% cost reduction. Episode costs showed a nearly linear increase based on the length of time taking opioids, as well as with a higher average daily dose. Cost increases with opioids were broad across service categories even when comparing within the same severity-adjusted episodes of care., Conclusions: The data suggest a clinically and statistically significant increase in episode costs associated with opioid use for degenerative joint disease of the spine, both within and between patients, and higher costs with a longer duration of opioid use as well as with higher daily dosages. Given the health consequences surrounding the overuse of opioids, concerted efforts to move towards a non-opioid pain control strategy are needed.

Background: Many patients receive prescription opioids at hospital discharge after surgery, yet little is known regarding how often these opioids go unused. We estimated the prevalence of unused opioids, use of nonopioid analgesics, and storage and disposal practices after same-day and inpatient surgery., Methods: In this prospective cohort study at a large, inner-city tertiary care hospital, we recruited individuals ≥18 years of age undergoing elective same-day or inpatient joint and spine surgery from August to November 2016. Using patient surveys via telephone calls, we assessed patient-reported outcomes at 2-day, 2-week, 1-month, and 6-month intervals, including: (1) stopping opioid treatment and in possession of unused opioid pills (primary outcome), (2) number of unused opioid tablets reported after stopping opioids, (3) use of nonopioid pain treatments, and (4) knowledge and practice regarding safe opioid storage and disposal., Results: Of 141 eligible patients, 140 (99%) consented (35% taking preoperative opioids; mean age 56 years [standard deviation 16 years]; 47% women). One- and 6-month follow-up was achieved for 115 (82%) and 110 patients (80%), respectively. Among patients who stopped opioid therapy, possession of unused opioids was reported by 73% (95% confidence intervals, 62%-82%) at 1-month follow-up and 34% (confidence interval, 24%-45%) at 6-month follow-up. At 1 month, 46% had ≥20 unused pills, 37% had ≥200 morphine milligram equivalents, and only 6% reported using multiple nonopioid adjuncts. Many patients reported unsafe storage and failure to dispose of opioids at both 1-month (91% and 96%, respectively) and 6-month (92% and 47%, respectively) follow-up., Conclusions: After joint and spine surgery, many patients reported unused opioids, infrequent use of analgesic alternatives, and lack of knowledge regarding safe opioid storage and disposal. Interventions are needed to better tailor postoperative analgesia and improve the safe storage and disposal of prescription opioids.

Ehlers-Danlos syndrome (EDS) is an emerging cause of skeletal fragility. Mechanism of bone damage are probably multifactorial in line with the different skeletal phenotypes that can be found in clinical practice. A structured approach to clinical management of bone metabolic complication in EDS is proposed.

Back pain is the second most common reason for primary-care physician visits after the common cold. New understanding of the spine pathophysiology and biomechanics led to the development of novel injectable biomaterials to treat those pain generators. Although not all biomaterials are currently ready for common use, there is significant interest by the medical community to invest time, resources, and energy to optimize these injectables. This review introduces basic concepts and advancements in the field of bioinjectables tailored for the vertebral body. Also, we highlight advances in injectable biomaterials which were presented at the Groupe de Recherche Interdisciplinaire sur les Biomatériaux Ostéoarticulaires Injectables (GRIBOI) (Interdisciplinary Research Society for Injectable Osteoarticular Biomaterials) meeting in March 2018 in Los Angeles, CA. Indeed, multidisciplinary translational research and international meetings such as GRIBOI bring together scientists and clinicians with different backgrounds/expertise to discuss injectable biomaterials innovations tailored for the interventional pain management field., (Published by Elsevier Inc.)

Background: Gout is a monosodium urate deposition disease which is prevalent worldwide. The usual manifestations are crystal arthropathy and tophi deposition in the soft tissues. Spinal tophi may also occur and are rarely reported, resulting in various clinical manifestations such as back pain, spinal cord compression, radiculopathy, and even mimicking epidural abscess and spondylodiscitis., Case Presentation: We report a case of a 42-year-old Chinese man with underlying gout who presented with back pain and radiculopathy. The diagnosis of spinal tophi was unsuspected and he was initially treated for epidural abscess and spondylodiscitis. He underwent a laminectomy and posterolateral fusion during which tophus material was discovered. He recovered and medications for gout were started., Conclusion: Spinal tophi are rare. The diagnosis is difficult and spinal tophi may be mistaken for epidural abscess, spondylodiscitis, or neoplasm.

Background: We present a rare case of Paget's disease (PD) with involvement of the lumbar spine over a period of 19 years. We discuss the diagnostic process to rule out alternative diagnoses and medical and surgical treatment strategies., Case Description: A 58-year-old man first diagnosed with PD in 1998 with solid involvement of the 4th lumbar vertebra has been undergoing periodic examinations over a period of 18 years. Since then, the patient has been treated conservatively with bisphosphonates. When conservative treatment options have been exhausted, surgery was indicated due to a progressively reduced ability to walk. Surgery with undercutting decompression via laminotomy was performed. PD was confirmed by biopsy. Bisphosphonate treatment was continued pre- and postoperatively. Follow-up examinations showed an improvement in clinical outcome measures., Conclusions: Conservative treatment remains the gold standard for PD with spinal involvement. This patient had been asymptomatic on bisphosphonate therapy for almost 17 years, but presented with new onset back pain. In such cases, fracture and rare conversion into sarcoma must be ruled out, and biopsy should be performed even in the absence of signs of malignancy. Currently, there are no clear treatment recommendations available in the literature regarding cases of PD with expansive growth and involvement of the spinal canal causing neurologic deficits. Furthermore, laminectomy has been shown to cause complications in up to 27% of cases with the risk of early postoperative death. In contrast, extended laminotomy and undercutting decompression should be considered.

Objective: To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies., Methods: Virtual and face-to-face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions., Results: Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response., Conclusion: Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO., (© 2017, American College of Rheumatology.)

Study Design: Systematic review and meta-analysis., Objective: Compare outcomes of adult patients undergoing spinal fusion surgery who receive and do not receive perioperative antifibrinolytics to reduce operative blood loss., Summary of Background Data: The clinical potential for antifibrinolytics such as tranexamic acid and epsilon aminocaproic acid to significantly reduce blood loss during adult spinal fusion surgery remains underexplored. Outcomes for assessment included operative blood loss, and other surgical, clinical, and haematological outcomes., Methods: We followed the recommended Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Electronic database searches identified 2041 for screening. Data were extracted and analyzed using meta-analysis of proportions., Results: A total of 11 randomized controlled trials with a total of 937 adult spinal fusion surgery patients were included for analysis. There were 472 (50%) patients who were treated with antifibrinolytics, with 345 of 472 (73%) and 127 of 472 (27%) receiving tranexamic acid and epsilon aminocaproic acid respectively. The use of antifibrinolytics was associated with significantly lower intraoperative (MD -127.08 mL; P = 0.002) and total blood loss (MD -229.76 mL; P < 0.00001), as well as incidence of blood transfusion (OR 0.58; P = 0.04). There was no significant difference with antifibrinolytic use in terms of many surgical parameters, including surgery duration (P = 0.50), overall complications (P = 0.21), and length of stay (P = 0.88). Finally, postoperative haemoglobin was significantly greater (MD 0.30 g/dL; P = 0.02) following antifibrinolytic use, with other haematological parameters mostly unaffected., Conclusion: Based on the highest level comparative evidence available, the possibility for blood loss reduction in adult spinal fusion surgery with the use of perioperative antifibrinolytics is not unreasonable, as it appears both efficacious and safe. In addition to further, larger investigations to validate the associations found in this study, practical aspects such as cost-benefit analysis, and long-term follow-up will further enhance our understanding., Level of Evidence: 1.