Novel evidence for the role of monomeric C reactive protein and WISP2 in the modulation of catabolic and inflammatory response in cartilage and intervertebral disc

Low back pain and osteoarthritis (OA) are the two main musculoskeletal diseases cause of disability worldwide, and intervertebral disc degeneration (IVDD) is considered the main cause of low back pain. A sustained inflammatory and catabolic state has been related to the origin and progression of both, OA and IVDD. This research work introduces monomeric C reactive protein (mCRP) pro-inflammatory and catabolic effects in healthy and degenerative human intervertebral disc cells and chondrocytes, suggesting its possible role in the pathophysiology of OA and IVDD. Furthermore, this thesis describes the adipokine WISP2 relevant roles in modulating the turnover of extracellular matrix in cartilage and how its downregulation may detrimentally alter the inflammatory environment in OA joints

Discogenic low back pain : lumbar spondylodesis revisited

Neurosurgeon deals with chronic low back pain patients almost daily. Most of these patients still have complaints of low back pain despite many different previous therapies. Surgical treatment is only to be considered in few cases of chronic low back pain sufferers. From this large group of chronic low back pain patients we have tried to select a small group of patients who might benefit fiom spondylodesis. This thesis is about the selection and treatment of this patient group. Their assumed source of pain and the results of surgical treatment will also be discussed. ... Zie: Summary

Anterior Lumbar Interbody Fusion (ALIF): a 360 degrees analysis

Lower back pain is a major cause of morbidity and disability in the western world. Lumbar fusion surgery is indicated in a minority of these patients and ALIF is one of the well-accepted techniques. This thesis represents the body of work, which addresses several aspects of ALIF surgery – a 360-degree overview. Initially we review the role of infection as a cause for degeneration of intervertebral disc, which is the commonest etiology for ALIF surgery. A systematic review demonstrated a high rate of bacterial growth in symptomatic disc degeneration but also raised the concern for the role of contamination and lack of adequate power. A pilot clinical study was undertaken which revealed a similar degree of bacterial infection. This was followed by a multicenter prospective case cohort study (DISC) to compare infection rates, evaluate contamination rate and review histopathological support for inflammation. At interim analysis, we found no difference in true infection rates between cases and controls, high rate of contamination in paraspinal tissue and no correlation between histopathological signs of inflammation and growth of organism. Indications for ALIF surgery and outcomes were evaluated, and ALIF had excellent clinical and radiological outcomes in degenerative disc disease, scoliosis and spondylolisthesis. Adjacent segment disease and failed posterior fusion had small sample size and were not as successful compared to other indications. We perform a clinical study to evaluate objective measurement of physical activity by accelerometers in spine surgery, demonstrating good patient compliance and no correlation between accelerometer measured physical activity and subjective outcome scores. Several radiological outcomes were also investigated. Utilizing a new standardization technique to measure foraminal area, we found ALIF significantly improved all the foraminal parameters, and that posterior disc height correlated with foraminal height restoration. A clinical study on i-factor as a bone graft substitute revealed a high rate of radiological fusion. We also found a reasonable sustained indirect reduction of spondylolisthesis by ALIF. Finally, we evaluated the complications of ALIF surgery particularly the vascular complications. The advantages of the team approach and lessons learnt to minimize complications are discussed

Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American society of interventional pain physicians (ASIPP) guidelines

Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ)

The use of health economics in the early evaluation of regenerative medicine therapies

The aim of this thesis is to help the RM industry avoid misguidedly investing in technologies that are unlikely to be cost-effective and reimbursed by healthcare providers. Health economics provides the tools to demonstrate value for money. These tools are typically used by healthcare providers to drive demand side decisions. However, they can be used by manufacturers to inform the supply side. I propose a simple approach, termed the headroom method. This ‘back of the envelope’ calculation is based on estimates of effectiveness of the proposed treatment towards the upper end of the plausible range. The method can be used either to inform an intuitive decision to continue or abandon development, or as a screening test to decide if more elaborate models are justified. One problem I encountered was the development of technologies without clearly defining the clinical problem. In particular, the marginal gain in benefit over alternative treatments is frequently overlooked. A large part of this thesis is therefore concerned with the clinical epidemiology of the conditions at which treatment is targeted. In this way, it was found, for example, the headroom for health gain from new treatment for inguinal hernia was much smaller than that for incisional hernias.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Next generation of growth-sparing techniques: preliminary clinical results of a magnetically controlled growing rod in 14 patients

Session 3A - Early Onset Scoliosis: Paper no. 33SUMMARY: Growth-sparing techniques are commonly used for the treatment of progressive EOS. The standard growing rod (GR) technique requires multiple surgeries for lengthening. The preliminary results of MCGR has shown the comparable outcomes to standard GR without the need for repeated surgery which can be expected to reduce the overall complication rate in GR surgery. INTRODUCTION: The growing rod (GR) technique for management of progressive Early-Onset Scoliosis (EOS) is a viable alternative but with a high complication rate attributed to frequent surgical lengthenings. The safety and efficacy of a non-invasive Magnetically Controlled Growing Rod (MCGR) has been previously reported in a porcine model. We are reporting the preliminary results of this technique in EOS. METHODS: Retrospective review of prospectively collected multi-center data. Only patients who underwent MCGR surgery and at least 3 subsequent spinal distractions were included in this preliminary review. Distractions were performed in clinic without anesthesia or analgesics. T1-T12 and T1-S1 height and the distraction distance inside the actuator were analyzed in addition to conventional clinical and radiographic data. RESULTS: Patients (N=14; 7 F and 7 M) had a mean age of 8y+10m (3y+6m to 12y+7m) and underwent a total of 14 index surgeries (SR: index single rod in 5 and DR: dual rod in 9) and 91 distractions. There were 5 idiopathic, 4 neuromuscular, 2 congenital, 2 syndromic and one NF. Mean follow-up (FU) was 10 months (5.8-18.2). Mean Cobb changed from 57° pre-op to 35° post-op and correction was maintained (35°) at latest FU. T1-T12 increased by 4 mm for SR and 10 mm for DR with mean monthly gain of 0.5 and 1.39, respectively. T1-S1 gain was 4 mm for SR and 17 mm for DR with mean monthly gain of 0.5 mm for SR and 2.35 mm for DR. The mean interval between index surgery and the first distraction was 66 days and thereafter was 43 days. Complications included one superficial infection in (SR), one prominent implant (DR) and minimal loss of initial distraction in three after index MCGR (all SR). Overall, partial loss of distraction was observed following 14 of the 91 distractions (one DR and 13 SR). This loss was regained in subsequent distractions. There was no neurologic deficit or implant failure. CONCLUSION: MCGR appears to be safe and provided adequate distraction similar to the standard GR technique without the need for repeated surgeries. DR patients had better initial curve correction and greater spinal height. No major complications were observed during the short follow-up period. The FDA has not cleared the drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an ‘off label’ use).postprin

Biocultural perspectives on birth defects in medieval urban and rural English populations.

The biocultural and epidemiological approaches have been used as investigative methods by which to assess the prevalence of birth defects of the axial skeleton among five English Medieval population samples (Raunds Fumells, Northamptonshire; the hospital/almshouse of St James and St Mary Magdalene, Chichester, West Sussex; St Helen-on-the-Walls, York; Wharram Percy, East Yorkshire, and the Augustinian Friary cemetery, Hull, Humberside).The author hypothesises that Medieval urban populations produced offspring with higher frequencies of skeletal defects because they were subject to the adverse health-mediating effects of higher population density. These include poor quality, frequently overcrowded living conditions, poor sanitation, increased rates of disease threat and transmission, poorer quality food and drink due to pollution and adulteration, and greater levels of industrial-related air and water pollution. The author proposes that this response was a consequence of the impaired interaction between a population-wide compromised nutritional status and a co-existing weakened immune response. It is proposed that rural populations will express significantly lower frequencies of the same skeletal defects, as they are not subject to the same adverse environmental effects of population density and urban living conditions. The results support this hypothesis among the four populations derived from burial grounds associated with residential areas, whilst the Hull population expresses a rural pattern of defect prevalence, raising questions of possibly limited, exclusive access to burial at that site, available to non-urban dwellers. The author suggests that similar reproductive effects may be found today in populations undergoing demographic transition, for example, those experiencing the process of urbanisation in the developing world, or those migrating to the developed West. The author also shows how the results, when viewed alongside the medical literature, may indicate the presence of soft-tissue anomalies which are invisible to those working with dry bone. Keywords: urban, rural, medieval, birth defects, congenital, urbanisation, population density, biocultural, epidemiology, spine, cleft palate, skeleton, archaeology, palaeopathology