Stereotactic Radiotherapy Followed by Surgical Stabilization Within 24 h for Unstable Spinal Metastases; A Stage I/IIa Study According to the IDEAL Framework

Background: Routine treatment for unstable spinal metastases consists of surgical stabilization followed by external beam radiotherapy (EBRT) or stereotactic body radiotherapy (SBRT) after a minimum of 1–2 weeks to allow for initial wound healing. Although routine treatment, there are several downsides. First, radiotherapy induced pain relief is delayed by the time interval required for wound healing. Second, EBRT often requires multiple hospital visits and only 60% of the patients experience pain relief. Third, spinal implants cause imaging artifacts hindering SBRT treatment planning and delivery. Reversing the order of surgery and radiotherapy, with dose sparing of the surgical area by SBRT, could overcome these disadvantages and by eliminating the interval between the two treatments, recovery, and palliation may occur earlier.Design: The safety of SBRT followed by surgical stabilization within 24 h for the treatment of unstable spinal metastases was investigated. Safety was evaluated using the Common-Toxicity-Criteria-Adverse-Events-4.0, with the occurrence of wound complications within 90-days being the primary concern.Results: Between June-2015 and January-2017, 13 patients underwent SBRT followed by surgical stabilization for unstable spinal metastases. The median time between SBRT and surgery was 17-h (IQR 5–19). None of the patients experienced wound complications. Improvements in pain and quality of life were observed over time for all patients.Conclusion: SBRT followed by surgical stabilization within 24 h for the treatment of unstable spinal metastases is safe. Palliation may be experienced earlier and with both treatments being performed in one hospital admission the treatment burden decreases

Lack of concentration-dependent local toxicity of highly concentrated (5%) versus conventional 0.5% bupivacaine following musculoskeletal surgery in a rat model

PURPOSE: Various sustained-release formulations incorporate high bupivacaine concentrations but data on local toxicity is lacking. This study explores local toxic effects of highly concentrated (5%) bupivacaine compared to clinically used concentrations in vivo following skeletal surgery, to assess the safety of sustained-release formulations with high bupivacaine concentrations. METHODS: Sixteen rats underwent surgery, in which screws with catheters affixed were implanted in the spine or femur in a factorial experimental design, allowing single-shot or continuous 72 h local administration of 0.5%, 2.5% or 5.0% bupivacaine hydrochloride. During the 30-day follow-up, animal weight was recorded and blood samples were obtained. Implantation sites underwent histopathological scoring for muscle damage, inflammation, necrosis, periosteal reaction/thickening and osteoblast activity. Effects of bupivacaine concentration, administration mode and implantation site on local toxicity scores were analyzed. RESULTS: Chi-squared tests for score frequencies revealed a concentration-dependent decrease in osteoblast count. Moreover, spinal screw implantation led to significantly more muscle fibrosis but less bone damage than femoral screw implantation, reflecting the more invasive muscle dissection and shorter drilling times related to the spinal procedure. No differences between bupivacaine administration modes regarding histological scoring or body weight changes were observed. Weight increased, while CK levels and leukocyte counts decreased significantly during follow-up, reflecting postoperative recovery. No significant differences in weight, leukocyte count and CK were found between interventional groups. CONCLUSION: This pilot study found limited concentration-dependent local tissue effects of bupivacaine solutions concentrated up to 5.0% following musculoskeletal surgery in the rat study population

A narrative review

Publisher Copyright: Copyright © 2022 Couto, Parreira, Power, Pinheiro, Madruga Dias, Novofastovski, Eshed, Sarzi-Puttini, Pappone, Atzeni, Verlaan, Kuperus, Bieber, Ambrosino, Kiefer, Khan, Mader, Baraliakos and Bruges-Armas.Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.publishersversionpublishe

The ethics of ‘Trials within Cohorts’ (TwiCs): 2nd international symposium - London, UK. 7-8 November 2016

On 7-8 th November 2016, 60 people with an interest in the ‘ Trials within Cohorts ’ (TwiCs) approach for randomised controlled trial design met in London. The purpose of this 2 nd TwiCs international symposium was to share perspectives and experiences on ethical aspects of the TwiCs design, discuss how TwiCs relate to the current ethical frame- work, provide a forum in which to discuss and debate ethical issues and identify future directions for conceptual and empirical research. The symposium was supported by the Wellcome Trust and the NIHR CLAHRC Yorkshire and Humber and organised by members of the TwiCs network led by Clare Relton and attended by people from the UK, the Netherlands, Norway, Canada and USA. The two-day sympo- sium enabled an international group to meet and share experiences of the TwiCs design (also known as the ‘ cohort multiple RCT design ’ ), and to discuss plans for future research. Over the two days, invited plenary talks were interspersed by discussions, posters and mini pre- sentations from bioethicists, triallists and health research regulators. Key findings of the symposium were: (1) It is possible to make a compelling case to ethics committees that TwiCs designs are ap- propriate and ethical; (2) The importance of wider considerations around the ethics of inefficient trial designs; and (3) some questions about the ethical requirements for content and timing of informed consent for a study using the TwiCs design need to be decided on a case-by-case basis

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painful overall. Current literature showed that bupivacaine induced dose-dependent myo-, chondro-, and neurotoxicity, as well as delayed osteogenesis and disturbed wound healing in vitro. These observations did not translate to animal and clinical research, where toxic phenomena were seldom reported. An exception was bupivacaine-induced chondrotoxicity, which can mainly occur during continuous joint infusion. To decrease opioid consumption and provide sustained pain relief following musculoskeletal surgery, new strategies incorporating high concentrations of bupivacaine in drug delivery carriers are currently being developed. Local toxicity of these high concentrations is an area of further research. This review appraises relevant in vitro, animal and clinical studies on musculoskeletal local toxicity of bupivacaine

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painful overall. Current literature showed that bupivacaine induced dose-dependent myo-, chondro-, and neurotoxicity, as well as delayed osteogenesis and disturbed wound healing in vitro. These observations did not translate to animal and clinical research, where toxic phenomena were seldom reported. An exception was bupivacaine-induced chondrotoxicity, which can mainly occur during continuous joint infusion. To decrease opioid consumption and provide sustained pain relief following musculoskeletal surgery, new strategies incorporating high concentrations of bupivacaine in drug delivery carriers are currently being developed. Local toxicity of these high concentrations is an area of further research. This review appraises relevant in vitro, animal and clinical studies on musculoskeletal local toxicity of bupivacaine

Clinical and radiological results 6 years after treatment of traumatic thoracolumbar burst fractures with pedicle screw instrumentation and balloon assisted endplate reduction

Background context  When used to fixate traumatic thoracolumbar burst fractures, pedicle screw constructs may fail in the presence of severe vertebral body comminution as the intervertebral disc can creep through the fractured endplates leading to insufficient anterior column support. Balloon-assisted endplate reduction (BAER) and subsequent calcium phosphate cement augmentation may prevent this event by restoring the disc space boundaries. The results of the first studies using BAER after pedicle screw fixation are encouraging, showing good fracture reduction, few complications, and minimal loss of correction at 2 years of follow-up.  Purpose   To present the clinical and radiological outcome of 20 patients treated for traumatic thoracolumbar burst fractures with pedicle screws and BAER after a minimum of 6 years follow-up.  Study design   Prospective trial.    Patient sample   Twenty consecutive neurologically intact adult patients with traumatic thoracolumbar burst fractures were included.  Outcome measures   Radiological parameters (wedge/Cobb angle on plain radiographs and mid-sagittal anterior/central vertebral body height on magnetic resonance imaging scans) and patient reported parameters (EQ-5D and Oswestry Disability Index) were used. Methods  All patients had previously undergone pedicle screw fixation and BAER with calcium phosphate cement augmentation. The posterior instrumentation was removed approximately 1.5 years after index surgery. Radiographs were obtained preoperatively, postoperatively, after removal of the pedicle screws, and at final follow-up (minimum 6 years post-trauma). Magnetic resonance imaging scans were obtained preoperatively, 1 month after index surgery, and 1 month after pedicle screw removal. Health questionnaires were filled out during the last outpatient visit.  Results  The pedicle screw instrumentation was removed uneventfully in all patients and posterolateral fusion was observed in every case. The mean wedge and Cobb angle converged to almost identical values (5.3° and 5.8°, respectively) and the mid-sagittal anterior and central endplates were reduced to approximately 90% and 80% of the estimated preinjury vertebral body height, respectively; this reduction was sustained at follow-up. Patient-reported outcomes showed favorable results in 79% of the patients. One patient required (posterior) reoperation due to adjacent osteoporotic vertebral body collapse after pedicle screw removal.  Conclusions Balloon-assisted endplate reduction is a safe and low-demanding adjunct to pedicle screw fixation for the treatment of traumatic thoracolumbar burst fractures. It may help achieve minimal residual deformity and reduce the number of secondary (anterior) procedures. Despite these positive findings, one in five patients experienced daily discomfort and disability

Comparison of in vitro and in vivo Toxicity of Bupivacaine in Musculoskeletal Applications

The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painful overall. Current literature showed that bupivacaine induced dose-dependent myo-, chondro-, and neurotoxicity, as well as delayed osteogenesis and disturbed wound healing in vitro. These observations did not translate to animal and clinical research, where toxic phenomena were seldom reported. An exception was bupivacaine-induced chondrotoxicity, which can mainly occur during continuous joint infusion. To decrease opioid consumption and provide sustained pain relief following musculoskeletal surgery, new strategies incorporating high concentrations of bupivacaine in drug delivery carriers are currently being developed. Local toxicity of these high concentrations is an area of further research. This review appraises relevant in vitro, animal and clinical studies on musculoskeletal local toxicity of bupivacaine

Delayed presentation to a spine surgeon is the strongest predictor of poor postoperative outcome in patients surgically treated for symptomatic spinal metastases

BACKGROUND CONTEXT: Symptoms associated with spinal metastases are often nonspecific and resemble noncancer-related symptoms. Therefore, patients with spinal metastases are at risk for delayed referral and treatment. Delayed presentation of symptomatic spinal metastases may lead to the development of neurological deficits, often followed by emergency surgery. PURPOSE: The aim of this cohort study was to analyze the effect of delayed referral and treatment of spinal metastases on clinical outcome. METHODS: We included all patients surgically treated for spinal metastases at our tertiary care center. Based on the (in)ability to undergo elective surgery, patients were identified as timely treated or delayed. Patient- and tumor-characteristics, surgical variables, and postoperative variables such as complication rate, the ability to return home and length of hospital stay were recorded and compared between the two groups. RESULTS: Based on the urgency of treatment at admission, 206 patients were identified as timely treated and 98 as delayed. At baseline, the two groups did not differ significantly except for the extent of neurological symptoms. Timely treated patients underwent less invasive procedures (52.9% vs 13.3% percutaneous pedicle screw fixations), had less median blood loss (200cc vs 450cc), shorter median admission time (7 vs 13 days), lower complication rate (26.2% vs 48.0%) and higher chances of being discharged home immediately (82.6% vs 41.1%) compared with delayed patients. Using multivariate regression models these correlations remained present independent of tumor prognosis, preoperative mobility, and American Society of Anesthesiologists-score. CONCLUSIONS: The delayed presentation of patients with spinal metastases to a spinal surgeon is strongly and independently associated with worse surgical and postoperative outcome parameters. Improvements in referral patterns could potentially lead to more scheduled care, negating the detrimental effects of delay