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1.
J Mater Chem B ; 12(7): 1730-1747, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-38294330

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.


Hydrogels , Spinal Diseases , Humans , Quality of Life , Minimally Invasive Surgical Procedures/methods , Neurosurgical Procedures/methods , Spinal Diseases/drug therapy , Spinal Diseases/surgery
2.
Pain Physician ; 25(7): E1105-E1113, 2022 10.
Article En | MEDLINE | ID: mdl-36288597

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.


Sarcopenia , Spinal Diseases , Spinal Stenosis , Male , Humans , Female , Aged , Spinal Stenosis/diagnosis , Injections, Epidural/methods , Psoas Muscles , Hand Strength , Sarcopenia/complications , Sarcopenia/drug therapy , Pain/drug therapy , Spinal Diseases/drug therapy , Steroids , Analgesics/therapeutic use
3.
J Orthop Surg Res ; 17(1): 397, 2022 Aug 31.
Article En | MEDLINE | ID: mdl-36045371

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.


Spinal Diseases , Spinal Fusion , Bone Morphogenetic Protein 2/adverse effects , Durapatite , Escherichia coli , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Multicenter Studies as Topic , Prospective Studies , Randomized Controlled Trials as Topic , Recombinant Proteins/adverse effects , Spinal Diseases/drug therapy , Spinal Fusion/methods , Transforming Growth Factor beta/adverse effects , Treatment Outcome
4.
Eur Spine J ; 31(7): 1765-1774, 2022 07.
Article En | MEDLINE | ID: mdl-35211807

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.


Discitis , Spinal Diseases , Anti-Bacterial Agents/therapeutic use , Debridement/methods , Discitis/drug therapy , Discitis/surgery , Endoscopy/methods , Humans , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Diseases/drug therapy , Treatment Outcome
5.
Clin Orthop Relat Res ; 480(1): 124-136, 2022 01 01.
Article En | MEDLINE | ID: mdl-34128841

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.


Anti-Bacterial Agents/therapeutic use , Osteomyelitis/drug therapy , Osteomyelitis/surgery , Spinal Diseases/drug therapy , Spinal Diseases/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Guideline Adherence , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Young Adult
6.
World Neurosurg ; 158: 182-188, 2022 02.
Article En | MEDLINE | ID: mdl-34875392

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.


Bone Substitutes , Mesenchymal Stem Cells , Spinal Diseases , Spinal Fusion , Animals , Bone Matrix/transplantation , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Diseases/drug therapy , Spinal Fusion/methods
7.
J Clin Invest ; 131(22)2021 11 15.
Article En | MEDLINE | ID: mdl-34779414

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 ß (TGF-ß) 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-ß 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.


Alopecia/drug therapy , Benzimidazoles/therapeutic use , Biphenyl Compounds/therapeutic use , Cerebral Infarction/drug therapy , High-Temperature Requirement A Serine Peptidase 1/physiology , Leukoencephalopathies/drug therapy , Spinal Diseases/drug therapy , Tetrazoles/therapeutic use , ADAMTS Proteins/analysis , Alopecia/complications , Animals , Cerebral Infarction/complications , Cerebrovascular Circulation/drug effects , Disease Progression , Extracellular Matrix Proteins/analysis , Latent TGF-beta Binding Proteins/analysis , Leukoencephalopathies/complications , Mice , Mice, Inbred C57BL , Recombinant Proteins/analysis , Spinal Diseases/complications , Transforming Growth Factor beta/physiology
8.
World Neurosurg ; 156: e64-e71, 2021 12.
Article En | MEDLINE | ID: mdl-34530148

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 (χ2= 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.


Bone Morphogenetic Protein 2/administration & dosage , Postoperative Complications/prevention & control , Spinal Diseases/drug therapy , Spinal Diseases/surgery , Spinal Fusion/trends , Transforming Growth Factor beta/administration & dosage , Bone Morphogenetic Protein 2/adverse effects , Cohort Studies , Diskectomy/adverse effects , Diskectomy/trends , Dose-Response Relationship, Drug , Humans , Longitudinal Studies , Postoperative Complications/chemically induced , Postoperative Complications/etiology , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Retrospective Studies , Spinal Fusion/adverse effects , Transforming Growth Factor beta/adverse effects
9.
Front Endocrinol (Lausanne) ; 12: 698963, 2021.
Article En | MEDLINE | ID: mdl-34335473

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.


Bone Cysts, Aneurysmal/drug therapy , Bone and Bones/drug effects , Denosumab/therapeutic use , Minerals/metabolism , Spinal Diseases/drug therapy , Adolescent , Bone Cysts, Aneurysmal/metabolism , Bone Cysts, Aneurysmal/pathology , Bone Density/drug effects , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bone Remodeling/drug effects , Bone and Bones/physiology , Child , Child Development/drug effects , Denosumab/adverse effects , Follow-Up Studies , Genu Valgum/chemically induced , Genu Valgum/diagnosis , Genu Valgum/pathology , Humans , Male , Spinal Diseases/metabolism , Spinal Diseases/pathology
10.
Sex Transm Dis ; 48(9): e126-e131, 2021 09 01.
Article En | MEDLINE | ID: mdl-33512899

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.


Spinal Diseases , Syphilis , Humans , Penicillins/therapeutic use , Spinal Diseases/diagnosis , Spinal Diseases/drug therapy , Syphilis/complications , Syphilis/diagnosis , Syphilis/drug therapy , Treponema pallidum
11.
Turk J Med Sci ; 51(1): 375-381, 2021 02 26.
Article En | MEDLINE | ID: mdl-32892542

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.


Benzoquinones/pharmacology , Laminectomy/adverse effects , Postoperative Complications , Spinal Diseases , Animals , Drug Administration Routes , Drug Monitoring/methods , Epidural Space/pathology , Fibrosis/drug therapy , Fibrosis/etiology , Laminectomy/methods , Nigella sativa , Phytochemicals/pharmacology , Postoperative Complications/diagnosis , Postoperative Complications/drug therapy , Rats , Spinal Diseases/diagnosis , Spinal Diseases/drug therapy , Spinal Diseases/etiology , Treatment Outcome
12.
World Neurosurg ; 145: e21-e31, 2021 01.
Article En | MEDLINE | ID: mdl-32916348

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.


Analgesics/therapeutic use , DNA Fingerprinting , Pain/drug therapy , Pain/genetics , Pharmacogenetics , Spinal Diseases/drug therapy , Spinal Diseases/genetics , Adult , Aged , Aged, 80 and over , Analgesics/pharmacokinetics , Analgesics, Opioid/pharmacokinetics , Analgesics, Opioid/therapeutic use , Back Pain/drug therapy , Back Pain/genetics , Female , Genetic Testing , Humans , Male , Middle Aged , Neck Pain/drug therapy , Neck Pain/genetics , Neurosurgical Procedures , Outpatients , Pain/complications , Pain Measurement , Pilot Projects , Polymorphism, Genetic , Prospective Studies , Spinal Diseases/complications
13.
Arch Osteoporos ; 15(1): 158, 2020 10 08.
Article En | MEDLINE | ID: mdl-33030619

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.


Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Osteoporosis/drug therapy , Teriparatide/therapeutic use , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Humans , Spinal Diseases/drug therapy , Spinal Diseases/surgery , Spinal Fusion/adverse effects , Teriparatide/adverse effects , Thoracic Vertebrae/drug effects , Thoracic Vertebrae/surgery , Treatment Outcome
14.
Clin Orthop Surg ; 12(3): 343-352, 2020 Sep.
Article En | MEDLINE | ID: mdl-32904035

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.


Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cardiovascular Diseases/chemically induced , Gastrointestinal Diseases/chemically induced , Spinal Diseases/drug therapy , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cross-Sectional Studies , Female , Guideline Adherence , Humans , Lumbar Vertebrae , Male , Middle Aged , Practice Patterns, Physicians' , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Spinal Diseases/complications
15.
PLoS One ; 15(9): e0237566, 2020.
Article En | MEDLINE | ID: mdl-32870946

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.


Bone Density Conservation Agents/therapeutic use , Calcium-Regulating Hormones and Agents/therapeutic use , Diphosphonates/therapeutic use , Spinal Fusion/methods , Teriparatide/therapeutic use , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/surgery , Spinal Diseases/drug therapy , Spinal Diseases/surgery , Thoracic Vertebrae/drug effects , Thoracic Vertebrae/surgery , Treatment Outcome
16.
Pain Physician ; 23(4S): S283-S294, 2020 08.
Article En | MEDLINE | ID: mdl-32942788

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.


Anti-Inflammatory Agents/administration & dosage , Hypothalamo-Hypophyseal System/drug effects , Pituitary-Adrenal System/drug effects , Triamcinolone/administration & dosage , Adrenal Insufficiency/chemically induced , Adult , Anti-Inflammatory Agents/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Hydrocortisone/analysis , Male , Middle Aged , Pain/drug therapy , Pain/etiology , Saliva/chemistry , Spinal Diseases/complications , Spinal Diseases/drug therapy , Triamcinolone/adverse effects
17.
Br J Community Nurs ; 25(8): 376-380, 2020 Aug 02.
Article En | MEDLINE | ID: mdl-32772722

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.


Anti-Bacterial Agents/administration & dosage , Bacteremia/drug therapy , Community Health Nursing/methods , Floxacillin/administration & dosage , Home Infusion Therapy/methods , Infusion Pumps , Osteomyelitis/drug therapy , Spinal Diseases/drug therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/prevention & control , Delivery of Health Care/methods , Elastomers , Humans , Infusions, Intravenous/instrumentation , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Retrospective Studies , SARS-CoV-2
18.
Spine (Phila Pa 1976) ; 45(15): 1081-1088, 2020 Aug 01.
Article En | MEDLINE | ID: mdl-32675616

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.


Analgesics, Opioid/administration & dosage , Pain, Postoperative/drug therapy , Patient Reported Outcome Measures , Spinal Diseases/drug therapy , Spinal Diseases/surgery , Adult , Aged , Analgesics, Opioid/adverse effects , Cohort Studies , Drug Administration Schedule , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/trends , Female , Humans , Longitudinal Studies , Male , Middle Aged , Opioid-Related Disorders/etiology , Opioid-Related Disorders/prevention & control , Pain, Postoperative/etiology , Prospective Studies , Retrospective Studies , Time Factors
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