人工股骨头置换治疗高龄患者股骨转子间骨折髓内钉失效的手术时机选择

目的:分析高龄患者股骨转子间骨折髓内钉失效后行人工股骨头置换术的手术时机选择。方法：2013年7月至2019年9月,采用人工股骨头置换术治疗股骨转子间骨折髓内钉固定失效后的17例高龄患者,根据从确诊内固定失效到行人工股骨头置换术的间隔时间将患者分为早期手术和延期手术两组。其中,早期手术组8例,男5例,女3例;年龄80~89（84.88±2.79）岁;间隔1~7（4.13±1.73） d。延期手术组9例,男4例,女5例;年龄80~89（84.22±3.03）岁;间隔15~30（25.56±4.36） d。比较两组患者手术时间、术中失血量、术后首次下地负重时间、术后住院时间、并发症例数及死亡例数。术后1、12个月采用Harris评分评价髋关节功能。结果：术后患者切口愈合良好,早期手术组泌尿道感染1例;延期手术组中,肌间静脉血栓2例,肺部感染1例,泌尿道感染3例,假体脱位1例。17例患者均获随访,时间12~16（14.76±1.86）个月。两组手术时间、术中失血量、死亡例数比较差异无统计学意义（P>0.05）;两组术后首次下地负重时间、术后住院时间、并发症例数比较,差异有统计学意义（P<0.05）。术后1个月两组患者Harris评分比较,差异有统计学意义（P<0.05）;术后12个月两组患者Harris评分比较,差异无统计学意义（P>0.05）。结论：高龄患者股骨转子间骨折髓内钉固定失效后,早期手术同延期手术相比,其死亡率及最终髋关节功能无明显差异,但早期行人工股骨头置换术能够让患者更早下地负重,缩短住院时间,有效减少并发症率,尽快恢复髋关节功能。     

Development and assessment of a complete-detoxication strategy for Fuzi (lateral root of Aconitum carmichaeli) and its application in rheumatoid arthritis therapy

Ethnopharmacological relevance

Fuzi (lateral root of Aconitum carmichaeli) is a popular traditional Chinese medicine well known for its both therapeutic and high-toxic activities. Its toxic alkaloid ingredients, mainly aconitine, mesaconitine, and hypaconitine, are responsible for the high toxicity. However, to date, no detoxication strategy is available to completely eliminate Fuzi's toxicity, and, whether Fuzi's efficacy could be kept after detoxication, remain unknown and debatable.

Materials and methods

The purpose of this study was to establish and validate a complete-detoxication strategy for Fuzi via acute toxicity test, to clarify the detoxication mechanism by HPLC and titrimetric analyses, and to evaluate the therapeutic effect of detoxicated Fuzi on adjuvant arthritis (AA). Three processed Fuzi (Bai-fu-pian) with 30-min, 60-min, and 120-min decoctions, respectively, named dBfp-30, dBfp-60, and dBfp-120, were prepared for this study. For the acute toxicity test, their oral doses to male and female Kunming mice were up to 70–190 g/kg body weight, and their toxicological profiles were evaluated by median lethal dose (LD₅₀), maximal tolerance dose (MTD), minimal lethal dose (MLD), no-observed-adverse-effect-level (NOAEL), and time–concentration–mortality (TCM) modeling methods using a 14-day schedule with up to five doses. The HPLC analysis was performed to determine the detoxication-induced changes in composition and amount of aconitine, mesaconitine and hypaconitine in Fuzi, whilst the titrimetric method was adopted to estimate the amount changes of Fuzi's total alkaloids. AA model was established by incomplete Freund's adjuvant injection in Wistar rats, and the animal's physiological (body weight, food intake, etc.), clinical (hind paw volume), and immunological (IL-1 and TNF-α) parameters were assessed as markers of inflammation and arthritis.

Results

With increasing decoction time, the acute toxicity of detoxicated Fuzi became decreased in the following order: dBfp-30 (LD₅₀ of 145.1 g/kg; MTD of 70 g/kg; MLD of 100 g/kg; NOAEL of 70 g/kg) >dBfp-60 (too large LD₅₀; MTD of 160 g/kg; MLD of 190 g/kg; NOAEL of 100 g/kg) >dBfp-120 (no LD₅₀; unlimited MTD; unlimited MLD; NOAEL of 130 g/kg). dBfp-30 and dBfp-60 displayed the toxicity at a dose-dependent manner with maximum mortalities reaching 100% and 50% respectively, whereas no mortality or signs of intoxication was induced by dBfp-120. The chemical analyses revealed a dramatic reduction of the toxic alkaloids as well as total alkaloids in Fuzi after the detoxication, from which no level of aconitine and only minimum residual of mesaconitine (0.56±0.02 μg/g) and hypaconitine (8.73±0.13 μg/g) were detected in dBfp-120. However, no significant difference of total alkaloid amount was found among dBfp-30, dBfp-60, and dBfp-120 (P>0.05), suggesting an equivalent conversion from toxic alkaloids to its non-toxic derivants in dBfp-120. Further, also no significant differences were seen among dBfp-30, dBfp-60, and dBfp-120 for the therapeutic effects on physiological, clinical, and immunological parameters in AA rat, indicating that dBfp-120 is of non-toxicity and efficacy.

Conclusions

A complete-detoxication strategy has been developed successfully for ensuring the safe and effective use of Fuzi. The detoxication mechanism associated with elimination of toxic alkaloids has kept Fuzi's efficacy, indicating a non-interdependent relationship between its efficacy and toxicity. This is the first report on such an optimal detoxication strategy and on the application of detoxicated Fuzi in AA. It may provide in depth understanding to the toxicological and pharmacological profiles of Fuzi and further benefit the herbal drug development with safety and efficacy for disease especially RA therapy.     

Clinical outcomes of open reduction and internal fixation for intra-articular complex tibial plateau non-union with 3-year minimum follow-up

BackgroundA tibial plateau fracture is one of the most challenging fractures for both knee and trauma surgeons because of the high incidence of post-traumatic knee osteoarthritis. To our knowledge, there has been no study concerning the clinical outcomes after surgery in patients with non-union of complex intra-articular tibial plateau fractures. Thus, the present study aimed to assess and report the clinical outcomes in them.MethodsThe study included four patients with non-union of complex tibial plateau fractures who underwent failed initial fixation treatment or could not undergo initial fixation owing to concomitant injury and who were followed up with a diagnosis of non-union for a minimum of 6 months. At the latest follow-up, patient-reported outcome measures, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford 12-item Knee Score (OKS), were assessed. Additionally, the knee range of motion (ROM) was evaluated.ResultsThe mean duration from the initial surgery to revision surgery was 8.8 months, and the mean duration from the revision surgery to fracture union was 4.8 months. At the latest follow-up, the mean WOMAC score was 9.8 and the mean OKS was 43.5. Additionally, the mean knee ROM values were ?11 degrees of extension and 100 degrees of flexion. All four patients had become able to walk without any aid after averaged 4.5-years follow up.ConclusionFavorable clinical outcomes can be achieved following revision surgery involving open reduction and IF in patients with non-union of complex tibial plateau fractures after failed initial treatment.Level of evidenceLevel IV, Case report.     

直接前入路全髋关节置换术应用氨甲环酸的有效性及安全性

目的：评估局部应用氨甲环酸（tranexamic acid,TXA）降低直接前入路（direct anterior approach,DAA）全髋关节置换术围手术期失血量的有效性和安全性。方法：自2013年7月至2018年9月,采用直接前入路初次全髋关节置换治疗的46例股骨头坏死患者,分为氨甲环酸组和生理盐水组,各23例。其中,氨甲环酸组中男14例,女9例,年龄52~72（63.70±5.34）岁,采用氨甲环酸3 g稀释于50 ml生理盐水中,在假体置换完毕后关节腔浸泡3 min;生理盐水组中男13例,女10例,年龄55~73（61.26±5.78）岁,采用等量生理盐水,相同方法关节腔浸泡。比较两组患者的失血量、血红蛋白值、输血例数、术后首次下地时间、血栓以及切口不良事件的发生率,术后1、3个月采用Harris评分评价髋关节功能。结果：术后患者切口愈合良好,两组无明显并发症发生。46例患者获随访,时间12~59个月,平均31.11个月。随访患者无髋部疼痛,髋关节功能有效改善,均未出现假体松动。术后氨甲环酸组和生理盐水组围手术期总失血量分别为（740.09±77.14）、（1 069.07±113.53）ml,术后24 h引流量为（87.61±9.28）、（233.83±25.62）ml,隐性失血量为（409.65±38.01）、（588.33±57.16）ml,手术前后血红蛋白差值为（24.78±2.19）、（33.57±2.95）g/L,差异有统计学意义（P<0.05）。两组术中失血量、深静脉血栓及肺栓塞的发生率、术后髋关节Harris评分比较差异无统计学意义（P>0.05）。。结论：直接前入路全髋关节置换术中局部应用氨甲环酸可安全、有效地减少围手术期失血量,且不增加血栓形成的风险,不影响关节功能正常恢复。