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Medical grade calcium sulfate bone incorporated with streptomycin in the treatment of thoracolumbar spinal tuberculosis
Abstract
Background: Medical grade calcium sulfate bone for bone defects after removal of spinal tuberculosis is controversial; however, patients undergoing long-term intramuscular injection of streptomycin for anti-tuberculosis show a poor compliance, and local application can overcome these shortcomings. Objective: To study the clinical efficacy and outcome of medical grade calcium sulfate bone incorporated with streptomycin and autogenetic bone graft combined with posterior debridement and instrumentation for thoracolumbar spinal tuberculosis. Methods: From March 2008 to June 2012, 18 patients with thoracolumbar spinal tuberculosis were treated with one-stage posterior debridement, medical grade calcium sulfate bone incorporated with streptomycin and autogenetic bone graft and instrumentation on the basis of regular anti-tuberculosis. Incision healing, adverse reactions and the change of clinical symptoms were recorded. Bone fusion and deformity correction were analyzed by the regular X-ray examination. Results And Conclusion: All the patients acquired satisfactory incision healing without obvious general adverse reactions. Clinical symptoms were differently relived. Kyphosis was corrected to some degree and the correction had no loss. Seventeen patients were cured after the first operation. Tuberculosis recurred in one patient 9 months after the first surgery and was cured after the second anterior surgery. X-ray examination showed that the calcium sulfate bone was clear 1 week after surgery and unclear 3 months after surgery. Bone fusion appeared 6 to 9 months after operation. These findings indicate that the application of medical grade calcium sulfate bone incorporated with streptomycin could achieve good effects in the treatment of thoracolumbar spinal tuberculosis, which is an excellent substitute material for bone graft. It not only could repair bone loss but also increase the concentration of anti-tuberculosis drugs.
Objective:
To review the characteristics and applications of different implantation in cervical tuberculosis surgery and the research progress of the new implantation.
Methods:
By consulting relevant domestic and foreign research literature on cervical tuberculosis, the classification, advantages, disadvantages, and prospects of implantations were analyzed and summarized.
Results:
The incidence of cervical tuberculosis has increased recently and has a high disability rate. Currently, the implantation in the surgical treatment of cervical tuberculosis are mainly divided into bone materials, metal materials, and bioactive materials; the above materials have their own advantages and disadvantages, for example, the amount of autologous bone is limited, the complications of allogeneic bone are common, and the bone fusion effect of metal materials is poor. With the development of science and technology, the implantation are also more diverse.
Conclusion:
The choice of the implantation affects the bone fusion directly, furthermore, it affects the effectiveness of cervical tuberculosis, the development of new implantation provides a variety of options for the treatment of cervical tuberculosis.
Background:
Calcium sulfate belongs to synthetic ceramic group of bone graft substitutes having an osteoconductive property. Calcium sulfate is an easily available, economic bone graft substitute. It is a bio-inert material which over a period of weeks get resorbed and fibrovascular tissue takes its place which eventually allows neovascularisation and bone formation within the area. Use of calcium sulfate as a bone graft substitutes avoids the complications and morbidity associated with autograft like infection, second surgery, and finite amount of graft.
Material and methods:
A total of 15 patients with benign bone lesions and chronic osteomyelitis were operated and the osseous defects were filled with calcium sulfate which was comprehensively sterilized. Patients were followed with serial radiographs at six week intervals. Calcium sulfate resorption and new bone formation was studied.
Results:
Thirteen cases out of 15 showed calcium sulphate resorption and new bone incorporation. Calcaium sulphate resorption occurred at an average of 14.5 weeks (range,13-18weeks) whereas new bone incorporation occurred at an average of 6months ( range,5-7months). Thirteen patients out of these 15 cases returned to full activities of daily living. One patient had pathological fracture at the osseous defect postoperatively. One patient with GCT of distal end of tibia had recurrence of tumor and had to undergo second surgery.
Conclusion:
Although autogenous bone graft is the gold standard for bone grafting, it has limitations like finite amount, additional surgery and donor site morbidity. Calcium sulphate is safe, efficient and easily available bone graft substitute in the treatment of osseous defects. Most common complication encountered was aseptic serous discharge. Functional results were favorable in most of the cases.
The spinal column is involved in less than 1% of all cases of tuberculosis (TB). Spinal TB is a very dangerous type of skeletal TB as it can be associated with neurologic deficit due to compression of adjacent neural structures and significant spinal deformity. Therefore, early diagnosis and management of spinal TB has special importance in preventing these serious complications. In order to extract current trends in diagnosis and medical or surgical treatment of spinal TB we performed a narrative review with analysis of all the articles available for us which were published between 1990 and 2011. Althoug h the development of more accurate imaging modalities such as magnetic resonance imaging and advanced surgical techniques have made the early diagnosis and management of spinal TB much easier, these are still very challenging topics. In this review we aim to discuss the diagnosis and management of spinal TB based on studies with acceptable design, clearly explained results and justifiable conclusions.
In developing countries, a recognized etiology of paraplegia can be tuberculous radiculomyelitis or tuberculomas, especially in patients with evidence of either active or latent tuberculosis. These entities should also be considered in high-risk patients or in patients who have emigrated from regions with a high prevalence of tuberculosis (TB). Both arachnoiditis and intradural tuberculomas are uncommon forms of spinal TB.
We report three cases of TB of the spinal cord in young males with paraplegia or paraparesis who were hospitalized over a one-year period. The clinical presentation and clinical course differed among the three patients: radiculomyelitis complicating tuberculous meningitis for the first patient and spinal tuberculomas in the other two. Neuroimaging with magnetic resonance imaging (MRI) was critical for diagnosis.
The therapy for spinal TB should be conservative since the neurologic deficits are mainly secondary to the inflammatory process. Usually these lesions respond to medical therapy alone, and with early diagnosis one can avoid unnecessary surgical intervention. In our limited clinical experience, corticosteroids (IV, intrathecal, or both) appear to have a beneficial effect.
The current available evidence for the use of bone graft substitutes in the management of subchondral bone defects associated with tibial plateau fractures as to their efficiency and safety has been collected following a literature review of the Ovid MEDLINE (1948–Present) and EMBASE (1980–Present).Nineteen studies were analysed reporting on 672 patients (674 fractures), with a mean age of 50.35 years (range 15–89), and a gender ratio of 3/2 males/females. The graft substitutes evaluated in the included studies were calcium phosphate cement, hydroxyapatite granules, calcium sulphate, bioactive glass, tricalcium phosphate, demineralised bone matrix, allografts, and xenograft.Fracture healing was uneventful in over 90% of the cases over a variant period of time. Besides two studies reporting on injectable calcium phosphate cement excellent incorporation was reported within 6 to 36 months post-surgery. No correlation was made by any of the authors between poor incorporation/resorption and adverse functional or radiological outcome. Secondary collapse of the knee joint surface ≥2 mm was reported in 8.6% in the biological substitutes (allograft, DBM, and xenograft), 5.4% in the hydroxyapatite, 3.7% in the calcium phosphate cement, and 11.1% in the calcium sulphate cases. The recorded incidence of primary surgical site and donor site infection (3.6%) was not statistically significant different, however donor site-related pain was reported up to 12 months following autologous iliac bone graft (AIBG) harvest. Shorter total operative time, greater tolerance of early weight bearing, improved early functional outcomes within the first year post-surgery was also recorded in the studies reporting on the use of injectable calcium phosphate cement (Norian SRS).Despite a lack of good quality randomised control trials, there is arguably sufficient evidence supporting the use of bone graft substitutes at the clinical setting of depressed plateau fractures.
The treatment of contaminated and infected bone defects remains an intractable problem and the ideal approach is to control infection and repair the bone defect at the same time. Thus, developing an osteoconductive bone graft composite with antibiotic and growth factor release capabilities as well as osteogenesis-matched degradation properties is necessary. A new calcium sulphate composite consisting of vancomycin and rhBMP-2 was developed, and the present study assessed its efficiency in vitro and in a rabbit tibial defect model.
Firstly, we detected the bioactivity of rhBMP-2 released from the composites by ALP assay in vitro. Then, the released vancomycin in bone tissue within 1 cm from implanted site was detected by HLPC at 1, 3, 5, 7, 14, 21 and 28 days after implantation. The rhBMP-2 concentration of tissues around the defects was also detected by ELISA. Histomorphometry and histomorphometrical analysis at 5, 14 and 28 days post-implantation was done for assessing its osteoinductivity for bone defects.
The results showed rhBMP-2 was still active in vitro at 29 days. In vivo, the composite released an initial bolus of vancomycin and rhBMP-2 to the bone followed by gradual release for more than 14 and 21 days, respectively. The histomorphometry indicated that the composite significantly augmented new bone formation in the defect compared to the control.
This composite may be a potential therapeutic agent for contaminated or infected bone defects due to its concomitant osteoinductive and antibiotic properties.
In reconstructive foot and ankle surgery, the use of bone graft is common. Whether for trauma, acquired or congenital deformities, arthrodeses, joint replacement, bone loss from infection, or bone tumor resection, the foot and ankle surgeon must be knowledgeable about current bone grafting options to make informed decisions. Innovation and technologic advances have produced an impressive and exciting array of options, advancing us closer to mimicking the gold standard: autograft. However, the sheer volume of available products makes it challenging for the foot and ankle surgeon to stay abreast of current bone graft technology. The purpose of this article is to simplify and classify current bone grafting options, discuss advantages and disadvantages, and provide relevant clinical examples.
Revision arthroplasty is a challenging aspect of the otherwise quite successful area of joint replacement surgery. The instable interaction between implant and host bone has often initiated a destructive process of inflammation and osteolysis, rendering the revision site sclerotic and with insufficient bone stock. One way of dealing with this is to build up a bed of tightly packed morselized bone graft to support the revision implant in a procedure often referred to as impaction grafting. Fresh frozen morselized femoral head allograft is the gold standard material for impaction grafting of the large defects usually involved in revision arthroplasty. The clinical outcome does not match that of primary arthroplasties. Implant subsidence is greater, implant survival shorter, and the bone graft is often not incorporated into living bone. The studies constituting this thesis have investigated ways of improving early implant fixation and bone graft incorporation. All studies used the same experimental canine model of early fixation and osseointegration of uncemented implant components inserted into a bed of impacted bone graft. Study I compared bone grafted implants where the morselized allograft was used alone or had been added rhBMP-2, the bisphosphonate pamidronate or a combination of the two. The main object was to see wether the previously observed growth factor related accelerated allograft resorption could be counteracted by the addition of an anti-catabolic drug. The study also compared HA-coated and non-coated porous Ti implants. The untreated control implants had better mechanical fixation than all other treatment groups. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. Study II investigated the addition of a bovine bone matrix lyophilisate (Colloss) to the allograft in three different doses. The main object was to see, whether the addition of a biological delivery device of low-dose osteogenic growth factors could provide a sufficient signal to increase the bioactivity of the bone graft without also yielding mechanical instability through increased allograft resorption. Allograft resorption increased with increased signal dose, but not to the extent that it affected implant fixation negatively at the observational time point. Mechanical implant fixation was doubled, and implant osseointegration and graft incorporation were improved. Study III compared a beta-TCP ceramic bone graft substitute (Ossaplast) with and without an osteogenic signal (Colloss E) to morselized allograft with and without the same signal. The object was to investigate, whether the addition of an osteogenic stimulus to a bio ceramic could replace biological allograft bone. The addition of an osteogenic signal improved early osseointegration of implants grafted with beta-TCP granules and increased their mechanical implant fixation to a level comparable to the allografted implants. All studies I-III confirmed that the topical addition of an osteogenic signal could increase implant osseointegration and the formation of new bone within a grafted defect. Another striking observation was the near-complete absence of fibrous tissue in the treated groups. The osseointegration of ceramic bone grafts improves when both the osteoconductive as well as the osteogenic components of bone are substituted. The effect on implant fixation of devices and pharmaceuticals that influence bone metabolism can be difficult to predict, as shown in study I. There seems to be a therapeutic window for these substances. This must be further explored prior to clinical use, as the adverse effects of overdosing bone anabolic and anti-catabolic substances can be detrimental.
The prognosis for survival has improved dramatically for cancer patients over the past three decades. Advances in systemic therapy have prolonged survival even in those who cannot be cured. The importance of managing spinal column disease and protecting the spinal cord has subsequently been amplified. Almost any patient presenting with detectable neurologic function and enough physical reserve to withstand an operation will benefit from a spinal stabilization, pain relief, and neural decompression; there are few exceptions. Advances in surgical technique and biomaterials have not only improved survival and functional outcome, they have diminished many of the postoperative complications that plagued earlier treatment techniques. Methods of preventing or correcting iatrogenic deformity have improved outcome. Newer fixation techniques promise to eliminate many of the causes of hardware and fixation failure previously seen. Improved medical management, antibiotics, and preoperative planning, along with techniques of preoperative embolization and early postoperative mobilization have made surgical management much less risky. Vertebrectomy, considered a last alternative in the past, is now coming to be seen as the conservative approach to tumor management in many situations. Appropriate surgical treatment can have a dramatic impact on function and outcome in patients with tumors of the spinal column, and should never be dismissed as an option without serious consideration. Advances in fixation systems, local and systemic therapy, and in our understanding of the biology of cancer promise even greater improvements for the future.
The object of this report is to highlight some of the less known atypical features of spinal tuberculosis (TB) in the hope of facilitating early diagnosis. Pure neural arch and sacral TB is rare and the co-existence of these two as widely separated skip lesions in the same patient is even rarer.
An unusual case of tuberculous process affecting the sacrum as well as the neural arches of upper cervical vertebrae is presented. Neither the clinical features nor the imaging techniques, including radiography, bone scintigraphy, computed tomography, and magnetic resonance imaging, were helpful in establishing the diagnosis. The destructive lesion of the sacrum with a rectally palpable presacral mass was thought to be a chordoma or chondrosarcoma until the patient developed upper cervical cord compression with an extradural myelographic block. Development of this second destructive lesion involving the posterior spinal elements (the neural arch) led to a diagnosis of malignant spinal metastasis. The true diagnosis was only revealed by the histology of the solid tumor-like extradural mass in the upper cervical region and demonstration of acid-fast bacilli (AFB) in the lesion. Anti-TB chemotherapy resulted in complete resolution of sacral and cervical lesions as well as the neurologic deficits.
Differential diagnosis of the obscure spinal lesion should include tuberculosis, specifically the atypical forms; especially because complete cure is possible with early treatment and neurologic morbidity is high in neglected cases.
Pott disease and tuberculosis have been with humans for countless millennia. Before the mid-twentieth century, the treatment of tuberculous spondylitis was primarily supportive and typically resulted in dismal neurological, functional and cosmetic outcomes. The contemporary development of effective antituberculous medications, imaging modalities, anesthesia, operative techniques and spinal instrumentation resulted in quantum improvements in the diagnosis, management and outcome of spinal tuberculosis. With the successful treatment of tuberculosis worldwide, interest in Pott disease has faded from the surgical forefront over the last 20 years. With the recent unchecked global pandemic of human immunodeficiency virus, the number of tuberculosis and secondary spondylitis cases is again increasing at an alarming rate. A surgical revisitation of Pott disease is thus essential to prepare spinal surgeons for this impending resurgence of tuberculosis.
To revisit the numerous treatment modalities for Pott disease and their outcomes. From this information, a critical reappraisal of surgical nuances with regard to decision making, timing, operative approach, graft types and the use of instrumentation were conducted.
A concise review of the diagnosis, management and surgical treatment of Pott disease.
A broad review of the literature was conducted with a particular focus on the different surgical treatment modalities for Pott disease and their outcomes regarding neurological deficit, kyphosis and spinal stability.
Whereas a variety of management schemes have been used for the debridement and reconstruction of tuberculous spondylitis, there has also been a spectrum of outcomes regarding neurological function and deformity. Medical treatment alone remains the cornerstone of therapy for the majority of Pott disease cases. Surgical intervention should be limited primarily to cases of severe or progressive deformity and/or neurological deficit. Based on the available evidence, radical ventral debridement and grafting appears to provide reproducibly good long-term neurological outcomes. Furthermore, recurrence of infection is lowest with such techniques. Posterior operative techniques are most effective in the reduction and prevention of spinal deformity.
Unlike historical times, effective medical and surgical management of tuberculous spondyitis is now possible. Proper selection of drug therapy and operative modalities, however, is needed to optimize functional outcomes for each individual case of Pott disease.
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are latently infected with MTB. Unfortunately, no new drugs except rifabutin and rifapentine has been marketed for TB in the US and other countries during the 40 years after release of rifampicin. There are a number of constraints that have deterred companies from investing in new anti-TB drugs. The research is expensive, slow and difficult, and requires specialized facilities for handling MTB. There are few animal models that closely mimic the human TB disease. Development time of any anti-TB drug will be long. In fact, clinical trials will require the minimum six-month therapy, with a follow-up period of one year or more. In addition, it is hard to demonstrate obvious benefit of a new anti-TB agents over pre-existing drugs, since clinical trials involve multidrug combination therapy using highly effective ordinary anti-TB drugs. Finaly, there is the perceived lack of commercial return to companies engaged in the development of new anti-TB drugs, because over 95% of TB cases worldwide are in developing countries. In this symposium, we reviewed the following areas. 1. Critical new information on the entire genome of MTB recently obtained and increasing knowledge of various mycobacterial virulence genes are greatly promoting the identification of genes that code for new drug targets. In this context, Dr. Namba reviewed the status of new types of compounds which are being developed as anti-TB drug. He also discussed the development of new antimycobacterial drugs according to new and potential pharmacological targets and the best clinical development plans for new-TB drugs in relation to corporate strategy. 2. Using such findings for mycobacterial genomes, bioinformatics/genomics/proteomics-based drug design and drug development using quantitative structure-activity relationships may be possible in the near future. In this context, Dr. Suwa and Dr. Suzuki reviewed the usefulness of chemical genomics in searching novel drug targets for development of new antituberculous drugs. The authors reviewed (1) the history and present status of chemical genomics that is defined as the systemic search for a selective small molecular modulator for each function of all gene products, (2) recent studies of the authors on profiles of the interactions between various kinds of human proteins and small molecule modulators using the new technology devised by Reverse Proteomics Research Institute, and (3) future prospects of the development of new antituberculous drugs based on chemical genomics. 3. It appears also promising to develop new types of drug administration systems using drug vehicles, which enable efficacious drug delivery to their target in vivo. Dr. Izumikawa, Dr. Ohno and Dr. Kohno reviewed the usefulness of liposome- and polymer-based technologies, which enable efficacious delivery of encapsulated drugs at required doses for prolonged periods of time with only a single shot without toxicity, and also enable highly targeted delivery of drugs to their target in vivo. They indicated that the applications of drug delivery system using conventional anti-mycobacterial agents are challenging to improve the compliance of treatment and better clinical outcome. 4. Immunoadjunctive therapy appears to be promising in improving outcome of clinical control of refractory mycobacterial infections, including MDR-TB and M. avium complex infection. Dr. Shimizu, Dr. Sato and Dr. Tomioka reviewed the present status of immunotherapy of mycobacterial infections in combination with antimycobacterial drugs. They indicated that the development of new classes of immunomodulators other than cytokines (IL-2, IFN-gamma, GM-CSF, IL-12, etc.) particularly those with no severe side-effects, are urgently needed. Their review dealed with some promising immunoadjunctive agents, especially ATP and its analogues, which potentiate macrophage antimycobacterial activity via purinergic P2 receptors. The aim of this symposium is to address the future prospects of the development of new drugs and drug regimens for anti-TB chemotherapy. There are a number of difficulties in drug-design for the development of new drug formulations with increased potential for antimycobacterial effects, excellent pharmacokinetics, and tolerability. It should be emphasized that the most urgent goal of chemotherapy of TB and MAC infections, especially that associated with HIV infection, is to develop highly active, low-cost drugs which can be used not only in industrialized countries but also in developing countries, since the incidences of AIDS-associated intractable TB and MAC infections are rapidly increasing in the latter. We strongly wish a great advance of fundametal and practical studies in developing such kinds of new anti-TB drugs in the near future. 1. Prospects for non-clinical or clinical development of new antituberculous drugs in relation to corporate strategy: Kenji NAMBA (New Product Research Laboratories I, Daiichi Pharmaceutical Co., Ltd.) Tuberculosis (TB) remains one of the deadliest threats to public health. No new anti-TB drugs have been brought into the clinic in the past 40 years. Current non-clinical works with progressed technology and Global Alliance for TB Drug Development, a non-profit organization established in 2000, accelerate research and development of faster-acting anti-TB compounds. We reviewed the status of new types of compounds which are being developed as anti-TB drug, such as diarylquinoline (TMC 207), nitroimidazole (PA-824 and OPC-67683), and moxifloxacin (MFLX). We also discussed the best clinical development plans for new-TB drugs in relation to corporate strategy. 2. Exploring novel drug targets through the chemical genomics approach and its possible application to the development of anti-tuberculosis drugs: Yorimasa SUWA (Reverse Proteomics Research Institute Co., Ltd.), Yohji SUZUKI (Teijin Ltd.) Recently, chemical genomics approach has been focused as an emerging technology for the drug discovery. In advance to a very large scale national project in US started last year, Reverse Proteomics Research Institute Co., Ltd. (REPRORI) has developed the core technologies for chemical genomics. Here we describe the outline of chemical genomics study, especially that of REPRORI, and discuss about its possible application to the development of anti-tuberculosis drugs. 3. Anti-mycobacterial agents and drug delivery: Koichi IZUMIKAWA, Hideaki OHNO, Shigeru KOHNO (Second Department of Internal Medicine, Nagasaki University School of Medicine) Mycobacterium infection is a major clinical concern in whole world. Since the newly developed anti-mycobacterial agents are few and still unavailable in clinical settings, the applications of drug delivery system using conventional anti-mycobacterial agents are challenging to improve the compliance of treatment and better efficacy. The efficacy of anti-mycobacterial agents modified by liposome or polymer based technology have been investigated and reported using various animal models. Drug delivery system increased and prolonged the drug concentrations at the blood and targeted organs and the duration of sustained drug release, respectively. These effects lead to decrease in the frequency of drug administrations dramatically and better efficacy rates. The studies, however, were performed only in animal models, the further investigations and evaluations in human are required for practical use. 4. Adjunctive immunotherapy of mycobacterial infections: Toshiaki SHIMIZU, Katsumasa SATO, Haruaki TOMIOKA (Department of Microbiology and Immunology, Shimane University School of Medicine) There is an urgent need to develop new antimicrobials and protocols for the administration of drugs that are potently efficacious against intractable mycobacterial infections. Unfortunately, development of the new drugs for solving this problem is not progressing. (ABSTRACT TRUNCATED)