The current status and development trend of hydrogel application in spinal surgery.

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.

[On the use of type I tropocollagen for local injection therapy of spine, upper and lower extremity disorders].

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.

Evaluation of the efficacy and safety of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion to treat degenerative spinal disease: a protocol of prospective, randomized controlled, assessor-blinded, open-label, multicenter trial.

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.

Endoscopic treatment of spondylodiscitis: systematic review.

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.

Treatment Guideline for Patients with Native Culture-negative Pyogenic Vertebral Osteomyelitis.

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.

Bone Graft Options in Spinal Fusion: A Review of Current Options and the Use of Mesenchymal Cellular Bone Matrices.

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.

Mineral and Bone Consequences of High Dose Denosumab Therapy to Treat an Aneurysmal Bone Cyst, a Child Case Report.

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.

Stereological and histopathological evaluation of the effect of Thymoquinone on peridural fibrosis following laminectomy in rats

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.

First Report of Pharmacogenomic Profiling in an Outpatient Spine Setting: Preliminary Results from a Pilot Study.

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.

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

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

Prevalence of Gastrointestinal and Cardiovascular Risk in Patients with Degenerative Lumbar Spinal Disease.

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.

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

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

Duration and Dosage of Opioids After Spine Surgery: Implications on Outcomes at 1 Year.

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.

Preoperative Opioid Use and Clinical Outcomes in Spine Surgery: A Systematic Review.

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.

Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials).

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.

Clinical management of dogs with presumptive diagnosis of thoracolumbar intervertebral disc disease: 164 cases (2006-2017) / Tratamento clínico de cães com diagnóstico presuntivo de doença do disco intervertebral toracolombar: 164 casos (2006-2017)

This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)

O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)

Do Prophylactic Antibiotics Reach the Operative Site Adequately?: A Quantitative Analysis of Serum and Wound Concentrations of Systemic and Local Prophylactic Antibiotics in Spine Surgery.

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 ±â€Š3.1 µg/mL which was decreased to 6.76 ±â€Š2.6 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 ±â€Š1.4 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 ±â€Š217.3 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 ±â€Š2.2 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.

A patient with extensive cerebral calcification due to pseudohypoparathyroidism: a case report.

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.