In vitro bacterial adherence to teicoplanin and calcium sulfate-soaked bone cement

The aim of this study was to assess in vitro the improvement in release kinetics for teicoplanin and the inhibition of bacterial adhesion on calcium sulfate-soaked PMMA discs. Calcium sulfate has been used in vivo and shown to be biocompatible, and prevention of bacterial adhesion may be expected with calcium sulfate-soaked polymethylmethacrylate (PMMA). Discs were made by adding teicoplanin and calcium sulfate in powder form to PMMA powder. The antibiotic concentration eluted from PMMA discs was assayed by agar diffusion assay. Nonadherent bacteria were removed by washing and adherent bacteria were detached by sonication. The suspension including nonadherent bacteria was seeded on sheep blood agar plate and incubated for 24 h at 37 degrees C for the growth of microorganisms. The teicoplanin released from discs containing calcium sulfate was higher than that released from discs which had not been soaked with calcium sulfate. The count of bacteria adhering to the calcium sulfate-soaked discs was lower than that from the discs without calcium sulfate. In conclusion, the addition of calcium sulfate to teicoplanin-loaded PMMA bone cement may provide local antibiotic concentrations higher than MIC values due to increased antibiotic release. Furthermore, calcium sulfate was found to be effective in reducing bacterial adherence to treated discs.     

Long-term intramuscular teicoplanin treatment of chronic osteomyelitis due to oxacillin-resistant Staphylococcus aureus in outpatients

Oxacillin-resistant staphylococci are the most serious pathogens in chronic osteomyelitis and only glycopeptides have been shown to be efficacious against them. We assessed the safety and efficacy of a regimen of teicoplanin 400 mg/day i.m. as long-term treatment in outpatients with osteomyelitis. A total of 76 patients received teicoplanin. Twenty-five patients had chronic prosthetic osteomyelitis (20 hip) and 51 patients had osteomyelitis caused by osteo-synthesis devices. Oxacillin-resistant Staphylococcus aureus was isolated in pure culture in 55 patients (72%). A total of 21 patients had polymicrobial infection with a total of 48 isolated strains. All patients were treated with teicoplanin 400 mg i.m. once-a-day alone or with other drugs for a minimum of 4 months. Only one patient had side effects requiring discontinuation of treatment. The teicoplanin dose was reduced to 200 mg/day i.m. in 2 patients to decrease creatinine clearance values. Seventy out of 76 patients were cured.     

Combined therapy of teicoplanin and caffeic acid phenethyl ester (CAPE) in the treatment of experimental mediastinitis in the rat

Post-sternotomy mediastinitis affects 1-3% of patients undergoing cardiac surgery and is lethal in 10-47% of these patients. We investigated the effect of an antioxidant/anti-inflammatory agent, caffeic acid phenethyl ester (CAPE), in the attenuation of inflammatory response induced by methicillin-resistant Staphylococcus aureus (MRSA) infection in a rat experimental mediastinitis model. Rats, divided into six equal groups, received MRSA precolonized stainless steel wire pieces implanted into their mediastinal spaces. Control group and CAPE control group received saline and CAPE 10 micromol/kg.day(-1 )respectively, where Group A received a single dose of teicoplanin 24 mg/kg i.m. for the first day and then 12 mg/kg.day(-1) . Group B received teicoplanin as in Group A plus CAPE 10 micromol/kg. day(-1 )intra-peritoneally. Group C received teicoplanin 60 mg/kg i.m. for the first day and then 30 mg/kg.day(-1 )and Group D received teicoplanin as in Group C plus CAPE 10 micromol/kg.day(-1) . By the end of 14 days rats were sacrificed and serum malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), urea and creatinine levels were evaluated. Mediastinal organ tissues were collected for histopathological analysis. Infection rates in all the drug-treated groups were lower than the control groups ( P=0.002) but statistical significance was attained only between the groups A and D ( P=0.018). In connective tissues and the peribronchial area polymorphonuclear leukocytic (PNL) infiltration in the treatment groups, although becoming very close, did not reach statistical significance (P =0.053, P=0.075, respectively). PNL infiltration especially in the peribronchial tissues of the Group B animals was found to be significantly less than the Control and CAPE Control groups with P values of 0.013 and 0.010, respectively. MDA and MPO levels were significantly lower in the treatment groups ( P<0.001 and P<0.001 respectively). Levels of the degradation products of NO were lower in treatment groups compared to two control groups (P=0.003, P= 0.005). NO levels in Group D were lowest among all treatment groups ( P=0.001). It has been demonstrated that although bacterial colonization can be controlled in mediastinitis, the inflammatory response persists. The combination of an antioxidant / anti-inflammatory agent, CAPE, added to standard antibiotic therapy might be effective in the treatment of post-sternotomy mediastinitis due to MRSA.     

Three-times weekly teicoplanin in the outpatient treatment of acute methicillin-resistant staphylococcal osteomyelitis: a pilot study

Treatment of osteomyelitis requires prolonged hospital stay, lengthy antibiotic therapy and adequate surgical debridement. Outpatient parenteral antibiotic therapy (OPAT) is a new approach to reduce patient discomfort and hospital costs. Teicoplanin, a glycopeptide antibiotic with a long half-life (72 hours), is one of the most useful drugs for OPAT. We performed a pilot study to assess the safety and efficacy of three-times weekly teicoplanin in the treatment of methicillin-resistant (MR) acute staphylococcal osteomyelitis. Ten patients with acute post-traumatic osteomyelitis were enrolled. Pathogens were MR Staphylococcus aureus (5 patients) and MR coagulase-negative staphylococci (5 patients). After a loading dose of 400 mg b.i.d. for 3 days, patients were treated with an intravenous dose of 1000 mg on Mondays and Wednesdays and with a 1200 mg dose on Fridays. Teicoplanin trough levels were maintained within a 10 to 20 mg/L range. If hardware removal had been possible at enrollment, treatment was carried out for at least 4 weeks. If, on the contrary, hardware removal had not been possible, teicoplanin was administered as suppressive therapy until hardware removal. Treatment was successfully performed in 9 out of 10 patients, whereas in one patient only improvement was achieved. Side effects were not recorded. Three times weekly teicoplanin seems to be a valuable option in the treatment of acute MR staphylococcal osteomyelitis. Further studies are warranted in order to better define the role of this new administration schedule in this field.     

万古霉素加硫酸钙骨粉治疗慢性骨髓炎

目的探讨医用硫酸钙骨粉（csc）结合万古霉素治疗骨髓炎的疗效。方法自2004年1月起,对11例骨髓炎患者,一期行清创扩创、充分引流或灌洗、抗生素骨水泥填充,二期采用医用硫酸钙骨粉（思迪骨粉Stimulan pellets）结合万古霉素植入骨髓炎病灶。结果所有填充自制备载药万古霉素骨粉的病例均获随访（10～20个月）,平均13个月,8例得到一次性治愈,3例手术后有渗出,经换药后愈合,未出现任何全身异常反应和并发症。结论载有万古霉素的硫酸钙骨粉（CSC）固化后较坚固,具有填充和释放抗生素作用,在解决骨缺损的同时,还可以维持局部抗生素浓度在较高水平,是治疗骨髓炎的较为理想的方法。     

异体DBM骨粒复合rhBMP-2及骨水泥材料修复骨缺损的实验研究

目的探讨异体脱钙骨基质（DBM）骨粒、骨水泥（BC）及重组人骨形态发生蛋白-2（rhBMP-2）复合材料修复实验性骨缺损的能力。方法复合材料植入兔实验性尺骨骨缺损部位（A组），B组植入纯骨水泥棒材作为对照。不同时间行组织学、印度墨汁动脉血管灌注及材料自然断面扫描电镜观察。结果材料植入第2周表面纤维组织样完整包膜形成，材料外周及两端血管形成密集，并向材料中长入；第4、8、12周新生血管明显增多，且深入至材料中央，新生间充质组织继续大量长入；包绕DBM骨粒的间充质组织部分4周转化为软骨。第8、12周软骨趋于成熟，可见含有造血骨髓的新生骨组织形成，其间可见较多的哈佛氏系统；同时，可见明显DBM骨粒被新生组织爬行吸收现象。第4周原自然裂隙部分已被结构紊乱的胶原纤维束充填。第8至12周，可见大量排列紊乱的矿化骨结构沿多方向长入，新生骨组织附于脱钙骨基质骨粒及骨水泥表面，原自然裂隙几近消失。植入B组材料者除外被纤维膜外余无变化。结论脱钙骨基质骨粒、骨形态发生蛋白、骨水泥复合材料具有良好的骨诱导及骨引导生成作用，是良好的骨缺损修复材料。     

The use of serial bone scans in assessing response of bone metastases to systemic treatment

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.     

Targeted and systemic radiotherapy in the treatment of bone metastasis

Cancer metastasis to the bone develops commonly in patients with a variety of malignancies, and is a major cause of morbidity and diminished quality of life in a significant proportion of cancer patients. The effective treatment of bone metastasis requires cooperation between medical, surgical and radiation oncologists. Radiotherapy, either in the form of targeted external beam radiation therapy, or systemic administration of radionuclides, plays a central role in treatment of symptomatic bone metastases. The appropriate external beam treatment techniques, dose and fractionation regimens for the treatment of symptomatic, localized bone metastasis have been established in prospective clinical trials. Large-field, hemi-body irradiation has been utilized for treatment of symptoms related to more widely disseminated bone metastases, but has been associated with substantial toxicity. Strontium-89 and Samarium-153 are widely available systemically administered radionuclides that are useful for the treatment of widely disseminated disease, and have largely supplanted the use of hemi-body irradiation. Combined with appropriate medical and surgical interventions, as well as the appropriate use of analgesics, radiotherapy is a well-tolerated and highly effective treatment for the palliation of symptomatic bone metastases.     

In vivo evaluation of teicoplanin- and calcium sulfate-loaded PMMA bone cement in preventing implant-related osteomyelitis in rats

The objective of this study was to evaluate the efficacy of teicoplanin- and calcium sulphate-loaded polymethylmethacrylate (PMMA) bone cements in preventing experimental implant-related osteomyelitis in rats. Four groups of antibiotic-loaded rods were prepared and were implanted into the lateral condylus of the rat femur after inoculation of Staphylococcus aureus. The effectiveness of these were assessed microbiologically, radiographically, and histopathologically. Radiographic evaluation revealed a significant reduction of periostal reaction and osteolysis in rats that received calcium sulphate- and teicoplanin-loaded rods. Histopathological evaluation confirmed these results. Acute infection and bone necrosis were found to be significantly lower in rats that had received calcium sulphate- and teicoplanin-loaded rods. The addition of calcium sulfate to teicoplanin-loaded PMMA bone cement appeared satisfactory as an antibiotic-carrying system for prophylaxis of experimental implant-related osteomyelitis, but further investigations are needed to reach definitive statements for clinical applications.     

Assessment of response to systemic therapy focusing on metastatic bone disease.

The 25-year-old rules for response evaluation developed by UICC and WHO still remain the cornerstone for response evaluation and documentation of treatment effects from systemic cancer treatment. Often, however, plain radiographs are insensitive to changes in tumour growth and disagree with clinical findings. Other methods of evaluation, such as biochemical markers and newer imaging technology may provide valuable additional information in these cases. Copyright2001 Harcourt Publishers Ltd Copyright 2001 Harcourt Publishers Ltd.     

Comparison of the efficacy of tigecycline and teicoplanin in an experimental methicillin-resistant Staphylococcus aureus osteomyelitis model

We evaluated the efficacy of tigecycline and teicoplanin in a rat model of MRSA osteomyelitis. Osteomyelitis was induced with an intramedullary injection of 10(8 )colony-forming units (cfu) of MRSA. After osteomyelitis formation was confirmed on Day 14, infected rats were randomly divided into three groups: tigecycline (n=13), teicoplanin (n=13), and no-treatment control (n=14). A 28-day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily) or intramuscular administration of teicoplanin (20 mg/kg daily) was administered. Rats were then sacrificed, and the tibias were harvested. The bones were weighed and then cultured. Our results indicated that bacterial growth was significantly reduced in teicoplanin and tigecycline groups, compared to the control group (p=0.019 and p=0.006, respectively). However, no difference was detected between the two antibiotic groups (p=1.000). No bacterial growth was detected in 7 out of 13 and 9 out of 13 specimens of the teicoplanin and tigecycline treated groups, respectively. Although this result was numerically in favor of tigecycline, the difference was not statistically significant (p=0.427). In conclusion, tigecycline, a novel antibiotic, appears as an effective alternative to teicoplanin in the treatment of osteomyelitis caused by MRSA.     

Tubercular osteomyelitis of the mastoid temporal bone

Infective osteomyelitis of mastoid temporal bone was a frequent complication of middle ear disease before the advent of antibiotics and chemotherapy, but now it is quite rare (Kelemen, 1957, Misra & Prakash, 1968). Tubercular osteomyelitis is rarer still (Shambaugh, 1959). A case of tubercular osteomyelitis of the mastoid temporal bone is reported.     

小剂量骨水泥PVP治疗多节段椎体压缩性骨折

目的 探讨采用小剂量骨水泥椎体成形术治疗多节段骨质疏松伴椎体压缩性骨折的临床效果。方法 回顾性研究自2006年９月至2011年８月我院采用小剂量骨水泥椎体成形术治疗46例多节段骨质疏松伴椎体压缩性骨折的病例。其中,男11例,女35例,年龄56～83岁,平均67.3岁。所有患者术前均行骨密度测定Ｔ值≤-2.5,提示骨质疏松,并行Ｘ线片、CT及MRI检查明确责任椎体及后壁完整情况。本组治疗的病例均为多节段椎体压缩性骨折,责任椎体分别分布在：胸６椎（１个）、胸７椎（１个）、胸８椎（２个）、 胸９椎（２个）、胸10椎（５个）、胸11椎（11个）、胸12椎（31个）、腰１椎（36个）、腰２椎（８个）,腰３椎（９个）、腰４椎（13个）、腰５椎（14个）等,本组治疗的病变椎体最少２个,最多４个,平均2.32个。所有患者均经单侧椎弓根穿刺椎体,１次对２个或２个以上责任椎体行小剂量骨水泥椎体成形术。术前、术后３天、１周、术后６个月随访时进行疼痛视觉类比评分（VAS）,评价临床治疗效果。结果 46例患者共行108个椎体成形术,平均１次2.32个椎体,单个椎体内骨水泥注射剂量约1.2～2.1 ml,平均（1.8±0.38）ml。所有患者定期随访,随访时间6～18个月（平均12.6个月）,术前患者VAS评分为7.95±0.82,术后３天VAS评分为4.48±0.80,随访时VAS评分为2.38±0.55,采用配对 t 检验对术前、术后随访时VAS评分进行统计学分析,差异有统计学意义（P＜0.001,α＝0.05）。结论 小剂量骨水泥椎体成形术作为一种微创手术,可有效地缓解多节段骨质疏松伴椎体压缩性骨折引起的疼痛症状,是一种有效的治疗方法。     

高粘度骨水泥在肿瘤颈椎骨转移中的应用

目的:探讨高粘度骨水泥在肿瘤颈椎骨转移中的应用效果。方法:回顾性分析我院2013年1月至2017年1月行高粘度骨水泥治疗的30例肿瘤颈椎骨转移患者相关资料,评价临床疗效、并发症情况,并测定治疗前后不同时间点测量数值评分量表（NRS）及Karnofsky评分。结果:骨水泥注射成功率100.00%,骨水泥平均用量4.0 ml;发生无症状骨水泥外漏1例;术后影像学检查显示骨水泥完全填充椎体28例,大部分椎体填充2例;与术前24 h比较,术后24 h、1周、3个月NRS评分均显著低,Karnofsky评分显著高,差异有统计学意义（P<0.05）;术后6个月Karnofsky评分（52.68±16.39）分,较术前24 h的（55.67±8.92）分差异无统计学意义（P>0.05）。结论:骨水泥注射能迅速减轻肿瘤颈椎骨转移引发的疼痛,能有效提高患者近期存活质量。     

Radiation therapy in the treatment of giant cell tumor of bone

Purpose: To assess the local control rate and potential complications of radiotherapy, and the factors influencing response to radiotherapy for primary and locally recurrent giant cell tumor of bone.Methods and Materials: Twenty patients were irradiated for giant cell tumor of bone between 1983 and 1993. Fourteen patients received radiotherapy at the time of primary diagnosis (10 had biopsy and 4 partial surgery) and 6 patients at the time of local recurrence (following additional surgery in 2). Fourteen patients had tumors of the extremity and six of the vertebral column. The radiotherapy dose ranged from 40–60 Gy in 15–30 fractions over 3–6 weeks. The response to radiotherapy was assessed by clinical and radiological criteria and the probable factors influencing response were analyzed.Results: The median follow-up period was 48 months (range, 4 months to 13 years). Local control was obtained in 18/20 patients. The two local failures were salvaged, one by reirradiation and the other by surgery. Only one patient died of giant cell tumor, following extensive bone marrow infiltration. There was no serious late toxicity or malignant transformation. The response to radiotherapy was not influenced by disease status at presentation, tumor site, radiotherapy schedule, or presence of soft tissue extension.Conclusions: Radiotherapy is effective in producing local control in primary as well as recurrent giant cell tumor of bone. There are no major complications and no significant risk of malignant transformation. Radiotherapy could be considered as the primary treatment modality in patients where surgery would produce functional deficits.     

Second-line systemic therapy for the treatment of metastatic renal cell cancer

The discovery of molecular mechanisms driving the progression of renal cell carcinoma (RCC) has led to the development of drugs that target RCC at the molecular level. Inhibition of VEGF-targeting pathways is successful as a front-line treatment in patients with metastatic RCC. In addition, bevacizumab/IFN-α, sunitinib and pazopanib are recommended for first-line use in good- or intermediate-risk patients, whereas temsirolimus is approved for poor-risk patients. Second-line options are valuable as these patients eventually progress. The present review addresses which drug is best in this second-line setting. Options for sequential therapy include tyrosine kinase inhibitor (TKI)–mTOR inhibitor or TKI–TKI sequences. We also address the question of whether sequential therapy with TKIs or the combination of VEGF followed by mTOR inhibition is the best choice for specific patients, and which sequence of TKIs is most beneficial.     

Second-line systemic therapy for the treatment of metastatic renal cell cancer

The discovery of molecular mechanisms driving the progression of renal cell carcinoma (RCC) has led to the development of drugs that target RCC at the molecular level. Inhibition of VEGF-targeting pathways is successful as a front-line treatment in patients with metastatic RCC. In addition, bevacizumab/IFN-α, sunitinib and pazopanib are recommended for first-line use in good- or intermediate-risk patients, whereas temsirolimus is approved for poor-risk patients. Second-line options are valuable as these patients eventually progress. The present review addresses which drug is best in this second-line setting. Options for sequential therapy include tyrosine kinase inhibitor (TKI)-mTOR inhibitor or TKI-TKI sequences. We also address the question of whether sequential therapy with TKIs or the combination of VEGF followed by mTOR inhibition is the best choice for specific patients, and which sequence of TKIs is most beneficial.     

New treatment paradigm with systemic therapy in intermediate-stage hepatocellular carcinoma

Since the approval of sorafenib for the treatment of unresectable hepatocellular carcinoma in 2007 (in 2009 in Japan), five more regimens have been approved: lenvatinib, and atezolizumab plus bevacizumab for first-line treatment, and regorafenib, cabozantinib, and ramucirumab for second-line treatment, which are currently available for clinical use. The positive results of durvalumab, a programmed cell death ligand 1 antibody, plus tremelimumab, an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, were also presented at the 2022 American Society Clinical Oncology Gastrointestinal Cancers Symposium as superior to sorafenib in prolonging the overall survival; this combination is expected to be approved by the end of 2022. These systemic therapies are changing the treatment paradigm not only for advanced hepatocellular carcinoma but also for intermediate-stage hepatocellular carcinoma. This review focuses on the role of systemic therapy in intermediate-stage hepatocellular carcinoma.

     

自制磷酸钙骨水泥对顺铂缓释作用的动物体内实验

目的:研究自制含顺铂磷酸钙骨水泥(CPC)植入体在实验动物体内的药物缓释性能。方法:将顺铂与CPC固相按1:19的比例混合后制成含顺铂磷酸钙骨水泥植入体,对照为不含顺铂的磷酸钙骨水泥植入体;以家兔为实验对象,实验组兔股骨远侧干骺端放置含顺铂植入体,对照组相同部位放置不含顺铂植入体并由耳缘静脉注射0.1%顺铂溶液,术后于不同时间点取血液及局部骨组织标本,用原子吸收分光光度仪检测顺铂含量。结果:与对照组相比,实验组兔血清中顺铂浓度低,局部骨组织中顺铂含量高,药物并不出现明显释放波峰,缓释体在兔体内释放顺铂时间长达1 6周以上,第1 6周时局部骨组织中顺铂含量仍有13.58μg/g,磷酸钙骨水泥植入体在局部骨组织中不出现明显溶解吸收现象。结论:自制含顺铂磷酸钙骨水泥载体对顺铂有缓慢而持久的体内释放作用,可望成为临床治疗骨肿瘤的一种新方法。