Do higher cut-off values for tuberculin skin test increase the specificity and diagnostic agreement with interferon gamma release assays in immunocompromised Bacillus Calmette-Guérin vaccinated patients?

Purpose

Immunocompromised patients with latent tuberculosis infection (LTBI) are at high risk of progression to active tuberculosis. Detection and treatment of LTBI in this group of patients are very important to control active tuberculosis. Tuberculin skin test (TST) and interferon gamma release assays (IGRAs) are two methods for detection of LTBI. Diagnostic agreement between two tests are poor especially in Bacillus Calmette-Guérin (BCG) vaccinated immunocompromised patients. In this study, we tried to figure out if the use of a higher cut-off for TST increases diagnostic agreement with IGRAs and TST specificity and or not.

Development of tuberculosis vaccines in clinical trials: Current status

Tuberculosis (TB ) is an important infectious disease worldwide. Currently, Bacillus Calmette‐Guérin (BCG ) remains the only TB vaccine licensed for human use. This TB vaccine is effective in protecting children against severe military TB but offers variable protective efficacy in adults. Therefore, new vaccines against TB are needed to overcome this serious disease. At present, around 14 TB vaccine candidates are in different phases of clinical trials. These TB vaccines in clinical evaluation can be classified into two groups including preventive pre‐ and post‐exposure vaccines: subunit vaccines (attenuated viral vectors or adjuvanted fusion proteins), and whole‐cell vaccines (genetically attenuated Mycobacterium tuberculosis (M. tb ), recombinant BCG , killed M. tb or M. vaccae ). Although, over the last two decades a great progress in the search for a more effective TB vaccine has been demonstrated there is still no replacement for the licensed BCG vaccine. This article summarizes the current status of TB vaccine development and identifies crucial gaps of research for the development of an effective TB vaccine in all age groups.     

On the intrinsic constraint of bacterial growth rate: M. tuberculosis’s view of the protein translation capacity

In nature, the maximal growth rates vary widely among different bacteria species. Fast-growing bacteria species such as Escherichia coli can have a shortest generation time of 20?min. Slow-growing bacteria species are perhaps best known for Mycobacterium tuberculosis, a human pathogen with a generation time being no less than 16?h. Despite of the significant progress made on understanding the pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly slow growth. From a global view, the intrinsic constraint of the maximal growth rate of bacteria remains to be a fundamental question in microbiology. In this review, we analyze and discuss this issue from the angle of protein translation capacity, which is the major demand for cell growth. Based on quantitative analysis, we propose four parameters: rRNA chain elongation rate, abundance of RNA polymerase engaged in rRNA synthesis, polypeptide chain elongation rate, and active ribosome fraction, which potentially limit the maximal growth rate of bacteria. We further discuss the relation of these parameters with the growth rate for M. tuberculosis as well as other bacterial species. We highlight future comprehensive investigation of these parameters for different bacteria species to understand how bacteria set their own specific growth rates.     

Coincidental diagnosis of tuberculous lymphadenitis: a case report

The aim of this case report was to present a case of multiple calcified tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in an endodontic clinic. A detailed discussion on the differential diagnosis of similar such calcification found in the same region is also presented. A 14‐year‐old girl was referred to our department with the complaint of painless swelling in the left side of the lower jaw. Clinical and radiographical examinations were performed, leading to the initial diagnosis of chronic periapical abscess. The patient's medical history was re‐evaluated. Advanced imaging and excisional biopsy were performed in order to confirm the final diagnosis. Regarding the presenting signs and symptoms of bilateral carious mandibular molars, a periapical inflammatory process was considered in the provisional diagnosis. A thorough examination and investigations were suggestive of cervical tuberculous lymphadenitis (scrofula), and the patient underwent excision of the same. The clinician should consider the possibility of chronic granulomatous inflammatory lesions in the differential diagnosis of radiopaque lesions.     

前路病灶清除植骨内固定结合局部灌洗化疗治疗下颈椎结核伴巨大脓肿

目的:评价前路病灶清除植骨内固定结合术后异烟肼生理盐水持续灌洗局部化疗治疗下颈椎结核伴巨大脓肿的临床疗效.方法:2001年6月～2010年6月收治下颈椎结核伴巨大脓肿患者13例,男8例,女5例;年龄28～62岁,平均44岁.病变累及部位:C3～C4 2例,C4～C5 3例,C5～C6 4例,C5 2例,C6 2例;脓肿累及节段:C3～C6 5例,C3～C7 3例,C4～C7 4例,C4～T1 1例.患者均存在颈部疼痛和不同程度的吞咽及呼吸困难,术前颈部疼痛VAS评分7～10分(8.1±1.3分).10例出现神经功能障碍,JOA评分5～12分(8.3±1.7分).术前血沉78±12mm/h,C反应蛋白65±17mg/L.均在全身抗结核药物治疗下采用颈前路结核病灶清除、钛网填充自体髂骨植骨内固定,术后异烟肼生理盐水持续局部灌洗化疗,并继续全身抗结核治疗12～18个月.随访观察患者临床症状改善、脓肿清除和植骨融合情况.结果:手术均顺利完成,所有患者无术中及术后并发症,术后异烟肼生理盐水持续灌洗14～26d,平均18d.未出现窦道、瘘管和脑脊膜感染.随访24～72个月,平均42个月,血沉和C反应蛋白在术后3个月内均恢复正常,手术节段在3～7个月(平均5.8个月)均得到骨性融合.颈部疼痛VAS评分末次随访时为0～3分(1.5±0.7分),与术前比较有显著性差异(P＜0.05).末次随访时JOA评分为12～17分(14.6±1.5分),与术前比较有显著性差异(P＜0.05).末次随访复查MRI均未见结核复发.结论:在全身规范抗结核药物治疗的前提下,采用前路病灶清除植骨内固定结合术后持续局部灌洗化疗治疗下颈椎结核伴巨大脓肿安全有效,临床效果满意.     

结核分枝杆菌耐利福平诊断试验的系统评价

目的采用Meta分析的方法评价LiPA和phage-based assays法检测结核分枝杆菌耐利祸平诊断试验的准确性：方法通过检索PubMed、EMbase、CBMWeb、CSJD、CJFD数据库和其他方式广泛收集文献：根据QUADAS质量评价标准评价纳入文献的质量，用Meta-Disc软件对其敏感度、特异度、阳性似然比、阴性似然比等进行合并分析，并进行异质性检验，对无异质性的研究绘制SROC曲线。结果最终纳入42篇文献：（1）LiPA法检测结核分支杆菌耐利福平时，7个研究以BACTEC460法为参考，合并敏感度0.98，合并特异度0.98，SROC（AUC）=0.9924；6个研究以proportion法为参考，合并敏感度0.97，合并特异度1.00，SROC（AUC）=0.9961；3个研究以BACTEC460、Proportion法作为参考，合斤敏感度0.92，合并特异度0.98，SROC（AUC）=0.9842；（2）噬菌体扩增法（商用）检测结核分枝杆菌耐利福平的7个研究，以BACTEC460、Proportion法为参考，合并敏感度0.95，合并特异度0.95，SROC（AUC）=0.9842，（3）噬菌体扩增法（内部的）检测结核分支杆菌耐利福平的7个研究，以BACTEC460、比例法、绝对浓度法和电阻率法为参考，其合并敏感度0.98，合并特异度0.98，SROC（AUC）=0.9949；（4）光素酶噬菌体报告技术检测结核分枝杆菌耐利福平的7个研究，以BACTEC460、比例法、绝对浓度法为参考，其合并敏感度0.98，合并特异度0.98，SROC（AUC）=0.9788。结论现有研究证实：（1）采用分离培养时，噬菌体检测法存检洲结核分枝杆菌耐利福平方面具有较高的敏感度和特异度，在提高耐多药结核病诊断准确性方面具有潜力、（2）LiPA任检测结俊分枝杆菌耐利福平方面也具有较高的敏感度和特异度，但直接应用临床标本检测时敏感度似乎稍有下降一上述结果尚需更多设计严谨、科学的临床试验进一步证实。     

一期手术经后路病灶清除植骨融合内固定治疗胸椎结核

目的探讨一期手术经后路结核病灶清除植骨融合内固定治疗胸椎结核的效果。方法 12例胸椎结核患者均采用一期经后路病灶清除、前后路植骨融合和后路钉棒系统内固定术。术后定期复查X线片了解Cobb角变化和椎间植骨融合情况,采用ASIA分级评定术后脊髓功能恢复情况。结果术中无大血管或脊髓损伤。患者均获随访,时间16～38个月。结核症状均消失无复发,无切口感染、窦道形成或内固定失败等并发症发生;复查血沉均正常。术后4～8个月X线片提示椎间植骨均融合,后路植骨融合时间6～9个月,内固定在位。末次随访Cobb角为18°～36°。脊髓功能ASIA分级:B级5例中有2例恢复至C级、3例无恢复,C级5例均恢复至D级,D级2例均恢复至E级。结论一期经后路清除胸椎结核病灶彻底,椎管减压可靠,行自体或同种异体骨植骨钉棒系统内固定可有效重建胸段脊柱的稳定性,矫形效果显著。     

颗粒植骨，钛网植骨和髂骨植骨在后入路单节段腰椎结核病灶清除术中的疗效研究

目的　比较颗粒植骨,钛网植骨和自体髂骨植骨在后入路单节段腰椎结核病灶清除术中的临床疗效。 方法　回顾性分析本科2015年7月至2020年9月接受后入路单节段腰椎结核病灶清除 + 植骨融合内固定术的98例患者,其中32例自体髂骨植骨,32例钛网植骨,34例颗粒植骨。主要的观察指标包括：手术时间,术中出血量,术后住院时间,VAS评分（visual analogue scale,VAS）,血细胞沉降率,C反应蛋白和美国脊髓损伤协会分级;次要参考指标：矫正和丢失Cobb角,植骨融合时间。记录所有参考数据并进行统计学分析。 结果　术后平均随访时间为28月（14 ~ 53月）。颗粒组手术时间（192.6±42.2）min,植骨融合时间（5.2±1.1）月,均优于髂骨块组（229.2 ± 61.6）min,（8.0 ± 2.9）月和钛网组（233.1±51.1）min,（8.6±5.6）月,P<0.05。术中出血量颗粒组（385.3±251.8）ml,少于钛网组（660.9 ± 486.4）mL,P<0.05;与髂骨块组（534.4 ± 395.4）ml无统计学差异,P＝0.122。术后末次随访患者腰椎节段后凸Cobb角均较术前显著改善（P<0.05）,丢失及矫正Cobb角各组间无统计学差异（P>0.05）。余指标3组间无统计学差异。 结论　与髂骨块植骨和钛网植骨相比,颗粒骨植骨简单易行,手术时间短,术中出血量少,术后植骨融合快,应用于后入路单节段腰椎结核术中,是一种安全,有效的植骨方式。     

腺苷脱氨酶活性检测在胸腔积液诊断中的临床价值

目的探讨腺苷脱氨酶（ADA）活性测定在胸腔积液诊断和抗结核疗效观察中的应用价值。方法采用北京利德曼生物技术有限公司ADA液体试剂盒，对127例胸腔积液患者胸腔积液中ADA活性进行检测，并对44例结核性胸腔积液和83例非结核性胸腔积液进行ADA活性比较及结核性胸腔积液治疗前、后ADA活性变化比较。结果127例患者胸腔积液中ADA活性增高共43例，其中结核组41例，非结核组2例，结核性胸腔积液组ADA活性为（40．67±10．22）U／L，明显高于癌性胸腔积液组[（5．98±5．56）U／L3及炎性胸腔积液组[（6．35±4．65）U／L3，差异有统计学意义（P〈0．05）；ADA诊断结核性胸腔积液的敏感性为93．2％（41／44），特异性为97．6％（81／83）。结核性胸腔积液患者ADA活性治疗前[（40．67±10．22）U／L3与治疗后[（9．12±6．24）U／L3比较，差异有统计学意义（P〈0．05）。结论胸腔积液ADA活性检测可以作为鉴别结核核性与非结核性胸腔积液的指标，并可作为抗结核治疗疗效观察的指标。     

Disseminated tuberculosis complicating anti-TNF-alpha treatment

An unusually large number of cases of tuberculosis, often of miliary or disseminated form, have been reported in patients receiving infliximab therapy for rheumatoid arthritis or Crohn's disease. We describe a patient with rheumatoid arthritis who was treated with infliximab and became systemically ill with Mycobacterium tuberculosis-disseminated infection. Patients who are candidates for treatment with tumour necrosis factor-alfa inhibitors should be evaluated for the presence of latent or active