Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: recommendations of the ORS spine section

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials

Eisenbahnbrücken auf der Erzbahnlinie in Nordschweden - Erhöhung der Achslasten von 14 auf 32.5 metrische Tonnen : [Railway bridges on the Iron Ore line in Northern Sweden - From axle loads of 14 to 32.5 metric tons]

Die Erzbahnlinie wurde um 1900 gebaut und überquert in ihrem Verlauf über 100 Brücken. Sie ist mehr als 500 km lang und verläuft von den Minen in Nordschweden zu den Häfen am Atlantik und an der Ostsee. Die ursprüngliche Achslast betrug 14 Tonnen. Zur Senkung der Transportkosten wurde die Achslast kontinuierlich erhöht, 1955 auf 25 Tonnen, 1998 auf 30 Tonnen und schliesslich auf 32,5 Tonnen im Jahr 2017 bzw. 2019. Der Erhöhung der Achslast ging jeweils ein Monitoring und eine Begutachtung der Brücken voraus. Dabei zeigte sich, dass viele dieser Brücken eine höhere Last tragen können, als ursprünglich beim Entwurf vorgesehen. Es werden Erfahrungen aus Studien vorgestellt, die zeigen ,dass durch gut geplante Erhaltungs- und Instalthaltungsprogramme/Ersatzneubauten viel Geld gespart werden kann. The Iron Ore Railway Line was built around 1900 and has more than 100 bridges. It has a length of ca 500 km and runs from the mines in northern Sweden to harbours on the Atlantic and on the Baltic. The original axle load was 14 ton. In order to lower freight costs, the axle loads has gradually been increased to 25 ton in 1955, to 30 ton in 1998,  and to 32.5 ton in 2017-2019. The increases in axle loads have been proceeded by monitoring and assessment studies of the bridges. Many of the bridges could carry a higher load than what it was designed for. Experiences from studies are presented showing that much money can be saved by a well planned maintenance and retrofitting/replacement program

Railway Bridges on the Iron Ore Line in Northern Sweden : From Axle Loads of 14 to 32,5 ton

The Iron Ore Railway Line was built around 1900 and has more than 100 bridges. It has a length of ca 500 km and runs from Kiruna and Malmberget in northern Sweden to the ice-free harbour in Narvik in Norway on the Atlantic and to Luleå in Sweden on the Baltic. The original axle load was 14 ton. The axle load has gradually been increased to 25 ton in 1955, to 30 ton in 1998 and to 32,5 ton in 2017. The increases in axle loads have been preceded by monitoring and assessment studies of the bridges. The capacity and need for strengthening or replacement of the bridges have been evaluated. Many of the bridges could carry a higher load than what it was designed for. Experiences from studies before the axle load was increased in 1998 and 2017 are presented and discussed.ISBN för värdpublikation: 978-1-5108-9208-8</p

A Parametric Study of an old Concrete Trough Bridge using non-linear Finite Element analysis

At least 20% of existing railway bridges in Sweden are reinforced concrete (RC) trough bridge that consist in a slab carried by two longitudinal main beams. As these bridges are getting old, there is an urging need to assess their remaining capacity with the aim of prolonging their service lives. The limited literature on the topic has pointed out that there is a significant difference between the capacity predicted by available codes and that obtained experimentally. In this paper, a review of the Bridge and Tunnel Management database (BaTMan) of railway infrastructure in Sweden, is carried out to gain an overview of the current state of the Swedish railway bridge, with focus on trough bridges. Then, a non-linear finite element model is calibrated using the experimental results of the previous testing of a decommissioned trough bridge. The model is used in a parametric study where the effect of key mechanical parameters on the capacity of trough bridges is studied. ISBN for host publication: 978-385748183-3</p

Pressure Distribution Patterns Between the Ballast and the Concrete Slab in Railway Trough Bridges

In Sweden, a substantial amount of railway bridges is approaching their intended lifespans and are planned to be replaced. However, it is not sustainable neither from a financial nor an environmental perspective to replace these bridges if they are still sound and safe. Thus, an evaluation of their actual capacity is required with the aim of extending their lifespans. A way to obtain a more accurate capacity is to determine the loads that are acting on them. Available literature points out the lack of experimental investigations on sleeper-ballast contact pressure, as well as on the stress distribution along and across the ballast. Consequently, railway bridge design has been based on traditional rather than rational assumptions, which can be quite conservative. In this paper, a review of models is carried out for evaluating stress patterns on the surface of the slab on ballasted concrete bridges. Then, a simplified finite element model of a concrete trough bridge, a common type of structure in Sweden, is used in a parametric analysis aimed to understand how the identified pressure distribution patterns affect the performance of this type of structure. Finally, with the purpose of studying how some parameters influence the bridge safety, a probabilistic reliability analysis is used. The reliability index beta (b) is obtained using the polynomial response surface method and its value is compared for different boundary condition scenarios. Also, the sensitivity factors for the considered random variables are compared and analyzed. Results show that the assumption of support condition and pressure pattern has a significant impact on the capacity, failure mode and probability of failure of this type of structure.ISBN för värdpublikation: 978-981-18-2016-8</p

Full Scale Test of a PC Bridge to Calibrate Assessment Methods

In this paper, experiences on the development of an assessment method for existing bridges are presented. The method is calibrated using the results of full-scale testing to failure of a prestressed bridge in Sweden. To evaluate the key parameters for the structural response, measured by deflections, strains in tendons and stirrups and crack openings, a sensitivity study based on the concept of fractional factorial design is incorporated to the assessment. Results showed that the most significant parameters are related to the tensile properties of the concrete (tensile strength and fracture energy) and the boundary conditions. A finite element (FE) model in which the results of the sensitivity analysis were applied, was able to predict accurately the load-carrying capacity of the bridge and its failure mode. Two additional existing prestressed concrete bridges, that will be used to improve further the method, are also described, and discussed.Funder: BBT; LKAB; Swedish Universities of the Built Environment</p

Comparing posterior cervical foraminotomy with anterior cervical discectomy and fusion in radiculopathic patients: an analysis from the Quality Outcomes Database

The objective of this study was to compare clinical and patient-reported outcomes (PROs) between posterior foraminotomy and anterior cervical discectomy and fusion (ACDF) in patients presenting with cervical radiculopathy. The Quality Outcomes Database was queried for patients who had undergone ACDF or posterior foraminotomy for radiculopathy. To create two highly homogeneous groups, optimal individual matching was performed at a 5:1 ratio between the two groups on 29 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, underlying pathologies, and levels treated). Outcomes of interest were length of stay, reoperations, patient-reported satisfaction, increase in EQ-5D score, and decrease in Neck Disability Index (NDI) scores for arm and neck pain as long as 1 year after surgery. Noninferiority analysis of achieving patient satisfaction and minimal clinically important difference (MCID) in PROs was performed with an accepted risk difference of 5%. A total of 7805 eligible patients were identified: 216 of these underwent posterior foraminotomy and were matched to 1080 patients who underwent ACDF. The patients who underwent ACDF had more underlying pathologies, lower EQ-5D scores, and higher NDI and neck pain scores at baseline. Posterior foraminotomy was associated with shorter hospitalization (0.5 vs 0.9 days, p < 0.001). Reoperations within 12 months were significantly more common among the posterior foraminotomy group (4.2% vs 1.9%, p = 0.04). The two groups performed similarly in PROs, with posterior foraminotomy being noninferior to ACDF in achieving MCID in EQ-5D and neck pain scores but also having lower rates of maximal satisfaction at 12 months (North American Spine Society score of 1 achieved by 65.2% posterior foraminotomy patients vs 74.6% of ACDF patients, p = 0.02). The two procedures were found to be offered to different populations, with ACDF being selected for patients with more complicated pathologies and symptoms. After individual matching, posterior foraminotomy was associated with a higher reoperation risk within 1 year after surgery compared to ACDF (4.2% vs 1.9%). In terms of 12-month PROs, posterior foraminotomy was noninferior to ACDF in improving quality of life and neck pain. The two procedures also performed similarly in improving NDI scores and arm pain, but ACDF patients had higher maximal satisfaction rates

How closely are outcome questionnaires correlated to patient satisfaction after cervical spine surgery for myelopathy?

Patient-reported outcomes (PROs) have become the standard means to measure surgical outcomes. Insurers and policy makers are also increasingly utilizing PROs to assess the value of care and measure different aspects of a patient's condition. For cervical myelopathy, it is currently unclear which outcome measure best reflects patient satisfaction. In this investigation, the authors evaluated patients treated for cervical myelopathy to determine which outcome questionnaires best correlate with patient satisfaction. The Quality Outcomes Database (QOD), a prospectively collected multi-institutional database, was used to retrospectively analyze patients undergoing surgery for cervical myelopathy. The North American Spine Society (NASS) satisfaction index, Neck Disability Index (NDI), numeric rating scales for neck pain (NP-NRS) and arm pain (AP-NRS), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scale were evaluated. The analysis included 1141 patients diagnosed with myelopathy, of whom 1099 had an NASS satisfaction index recorded at any of the follow-up time points. Concomitant radiculopathy was an indication for surgery in 368 (33.5%) patients, and severe neck pain (NP-NRS ≥ 7) was present in 471 (42.8%) patients. At the 3-month follow-up, NASS patient satisfaction index scores were positively correlated with scores for the NP-NRS (r = 0.30), AP-NRS (r = 0.32), and NDI (r = 0.36) and negatively correlated with EQ-5D (r = -0.38) and mJOA (r = -0.29) scores (all p < 0.001). At the 12-month follow-up, scores for the NASS index were positively correlated with scores for the NP-NRS (r = 0.44), AP-NRS (r = 0.38), and NDI (r = 0.46) and negatively correlated with scores for the EQ-5D (r = -0.40) and mJOA (r = -0.36) (all p < 0.001). At the 24-month follow-up, NASS index scores were positively correlated with NP-NRS (r = 0.49), AP-NRS (r = 0.36), and NDI (r = 0.49) scores and negatively correlated with EQ-5D (r = -0.44) and mJOA (r = -0.38) scores (all p < 0.001). Neck pain was highly prevalent in patients with myelopathy. Notably, improvement in neck pain-associated disability rather than improvement in myelopathy was the most prominent PRO factor for patients. This finding may reflect greater patient concern for active pain symptoms than for neurological symptoms caused by myelopathy. As commercial payers begin to examine novel remuneration strategies for surgical interventions, thoughtful analysis of PRO measurements will have increasing relevance

Cervical spondylotic myelopathy and driving abilities: defining the prevalence and long-term postoperative outcomes using the Quality Outcomes Database

Cervical spondylotic myelopathy (CSM) can cause significant difficulty with driving and a subsequent reduction in an individual's quality of life due to neurological deterioration. The positive impact of surgery on postoperative patient-reported driving capabilities has been seldom explored. The CSM module of the Quality Outcomes Database was utilized. Patient-reported driving ability was assessed via the driving section of the Neck Disability Index (NDI) questionnaire. This is an ordinal scale in which 0 represents the absence of symptoms while driving and 5 represents a complete inability to drive due to symptoms. Patients were considered to have an impairment in their driving ability if they reported an NDI driving score of 3 or higher (signifying impairment in driving duration due to symptoms). Multivariable logistic regression models were fitted to evaluate mediators of baseline impairment and improvement at 24 months after surgery, which was defined as an NDI driving score < 3. A total of 1128 patients who underwent surgical intervention for CSM were included, of whom 354 (31.4%) had baseline driving impairment due to CSM. Moderate (OR 2.3) and severe (OR 6.3) neck pain, severe arm pain (OR 1.6), mild-moderate (OR 2.1) and severe (OR 2.5) impairment in hand/arm dexterity, severe impairment in leg use/walking (OR 1.9), and severe impairment of urinary function (OR 1.8) were associated with impaired driving ability at baseline. Of the 291 patients with baseline impairment and available 24-month follow-up data, 209 (71.8%) reported postoperative improvement in their driving ability. This improvement seemed to be mediated particularly through the achievement of the minimal clinically important difference (MCID) in neck pain and improvement in leg function/walking. Patients with improved driving at 24 months noted higher postoperative satisfaction (88.5% vs 62.2%, p < 0.01) and were more likely to achieve a clinically significant improvement in their quality of life (50.7% vs 37.8%, p < 0.01). Nearly one-third of patients with CSM report impaired driving ability at presentation. Seventy-two percent of these patients reported improvements in their driving ability within 24 months of surgery. Surgical management of CSM can significantly improve patients' driving abilities at 24 months and hence patients' quality of life