李孔定治疗结核病经验

李孔定教授辨治结核，强调病证结合，以“扶正杀虫”为治疗大法，结合中药现代药理，善用地产草药，取得了卓越的临床疗效。     

Xpert MTB/RIF检测利福平耐药结核分枝杆菌的表型药敏结果分析

目的：分析Xpert MTB/RIF（Xpert）检测利福平耐药肺结核患者的表型药敏结果,为耐药结核病的治疗方案制定提供依据。方法：选取2015年1月至2020年12月期间在温州市中心医院感染科就诊,且痰液或肺泡灌洗液Xpert检测显示利福平耐药的结核患者,回顾分析患者结核分枝杆菌表型药敏结果。结果：570例Xpert检测利福平耐药患者获得一线抗结核药物药敏试验结果,总耐药顺位为利福平（90.18%）＞异烟肼（88.60%）＞链霉素（56.32%）＞乙胺丁醇（29.47%）;复治患者异烟肼、利福平、乙胺丁醇的耐药率（分别为94.50%、94.50%、35.78%）均高于初治患者（分别为84.94%、87.50%、25.57%）,差异有统计学意义（均P ＜0.05）;24 株菌株对一线抗结核药物均敏感,耐1种、2种、3种及4种药物分别有46株、156株、226株、118株;耐多药结核菌株476株,初治278株,复治198株,复治患者耐多药结核病比例更高（90.83% vs.78.98%,χ2=13.723,P ＜0.001）。302例Xpert检测利福平耐药患者获得二线抗结核药物药敏试验结果,总耐药顺位为氧氟沙星（35.76%）=阿米卡星（35.76%）＞卡那霉素（13.25%）=卷曲霉素（13.25%）;初治患者氧氟沙星耐药率低于复治患者（26.46% vs. 51.33%,χ2=19.044,P ＜0.05）;128株菌株对二线抗结核药物全敏感,耐1种、2种、3种及4种药物分别有111株、23株、21株、19株;泛耐药结核菌株50株,初治、复治各25株,复治患者泛耐药结核病比例更高（22.12% vs. 13.23%,χ2=4.051,P =0.044）。结论：异烟肼、氧氟沙星及阿米卡星耐药在Xpert利福平耐药肺结核患者中常见;复治患者耐药情况比初治患者更为严峻,应尽早获得一二线抗结核药物药敏结果,以指导临床用药。     

Newer trends in tubercular uveitis: a case series with systemic correlation

AIM: To determine the spectrum of uveitis, causes of visual loss in systemic tuberculosis, role of investigations and outcome after anti-tuberculosis treatment (ATT). METHODS: A retrospective study was conducted on 250 patients with systemic tuberculosis at a referral center in Chennai, South India from April 2016 to May 2019. Systemic workup comprised of Mantoux, chest X-ray, polymerase chain reaction (PCR) and QuantiFERON (QFT) TB Gold. Aqueous humor analysis by nested PCR or real time PCR (RT-PCR) and ancillary ophthalmic investigations such as fundus fluorescein angiography, optical coherence tomography were performed. RESULTS: Multifocal choroiditis and vasculitis were the most common manifestations and had a higher risk of recurrence. Pulmonary tuberculosis was more frequently associated with uveitis. Among those with extra-pulmonary tuberculosis miliary, bone and abdominal tuberculosis had uveitis. Complications such as cystoid macular edema, choroidal neovascular membranes and macular scarring caused visual loss. Aqueous humor analysis detected mycobacterium tuberculosis antigen. Collectively, systemic investigations such as chest X-ray, Mantoux test and those performed on blood samples such as PCR and QFT were positive in 39% of patients. In inconclusive patients, nested PCR and/or RT-PCR were done on aqueous humor samples and was diagnostic in 96%. A combination of tests was diagnostic in 92%. ATT in isolation in 71% and combined with corticosteroids in 29% was used for treatment of which signs of resolution and improvement in vision started as early as 6weeks in those who were started immediately on CS and ATT and longer than 3mo in those on ATT alone. Vision improved in 69%. Complete resolution occurred in 75% and worsening in 12%. CONCLUSION: A combination of investigations guided by clinical suspicion helps in precise diagnosis. In diagnostic dilemmas analysis of ocular samples is reliable and confirmatory. Prompt treatment with ATT and corticosteroids improved vision in 23% of our patients within 2mo. Vitritis with choroiditis causes cystoid macular oedema and requires longer duration of ATT. Screening all patients and a multidisciplinary approach in tuberculosis (active, healed or during treatment) is recommended.     

A cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence,risk factors and impact of anti-tuberculosis treatment

Background

To investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti-tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients.

Methods

A total of 1,904 tuberculosis patients were included in the study. A cross-sectional survey of the prevalence of leukopenia was initially conducted, and then factors influencing leukopenia were identified using Logistic regression analysis. Non-treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate COX proportional hazards models. Covariate analysis was used to assess the independent effect of different anti-tuberculosis regimens on peripheral blood leukocyte counts.

Results

Being female, advanced age and longer duration of previous anti-tuberculosis treatment (>6 month) were risk factors for leukopenia in tuberculosis patients, while secondary pulmonary tuberculosis, higher body mass index (BMI: 24−27.9 kg/m²), and higher degree of education (senior high school or above) were protective factors. Gender, vegetable consumption, drinking, pulmonary infection, other chronic diseases, and use of antibiotics were significantly associated with the development of leukopenia in patients on anti-tuberculosis treatment. In tuberculosis patients treated with anti-tuberculosis regimens not containing antibiotics, peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration. In tuberculosis patients treated with anti-tuberculosis regimens containing antibiotics, peripheral blood leukocyte levels showed a declining trend.

Conclusions

Female patients, patients at advanced age and recurrent tuberculosis patients having longer previous anti-tuberculosis treatment are high-risk populations for leukopenia. Attention should be paid to the influence of vegetable consumption and drinking, co-morbidities and use of antibiotics during anti-tuberculosis treatment.     

156例脊柱结核患者抗结核药物副作用临床分析

目的 阐明脊柱结核抗结核药物副作用发生情况及预防、处理措施.方法 对1998年1月至2007年12月间经我院确诊治疗的脊柱结核患者156例进行临床回顾性研究.结果 发生抗结核药物副作用68例(43.6%)114例次,以肝功能损害、位听神经损害、胃肠反应及视力损害为主(86.0%),因副作用致终止治疗4例,占2.6%.其中发生1种同类别副作用43例,2种副作用20例,3种以上副作用5例.抗结核药物的副作用多出现于用药早期,2个月内占67.5%.结论 抗结核药物引起的副作用较常见,临床常易忽视.若发生抗结核药物严重副作用,易引起严重后果,应引起临床医生高度重视.     

初治涂阳肺结核患者抗结核治疗不良反应发生现状及影响因素分析

目的探讨初治涂阳肺结核患者抗结核治疗不良反应发生现状,并分析其影响因素。 方法回顾性分析确诊并完成规范化治疗的初治涂阳肺结核患者280例的临床资料,总结抗结核治疗不良反应发生率、发生时间及类型,多因素Logistic回归分析其影响因素。 结果280例患者共发生抗结核治疗不良反应67例,不良反应发生率为23.93%;以单一症状不良反应为主,60例（89.55%）;大部分发生于强化期内,52例（77.61%）;以骨关节损害、肝功能损害、血液系统异常及胃肠道反应为主。不良反应组和非不良反应组年龄、体重指数、吸烟史、饮酒史、肝病史差异有统计学意义（P＜0.05或P＜0.01）。多因素Logistic回归分析显示：年龄＞60岁、体重指数＜18.5、吸烟史、饮酒史、肝病史是初治涂阳肺结核患者抗结核治疗不良反应发生的危险因素（P＜0.05或P＜0.01）。 结论初治涂阳肺结核患者规律抗结核治疗期间治疗相关不良反应以单一症状不良反应为主,大部分出现在强化期内,以骨关节损害、肝功能损害、血液系统异常及胃肠道反应为主;对年龄＞60岁、体重指数＜18.5、有吸烟史、有饮酒史、有肝病史的初治涂阳肺结核患者在行规律抗结核治疗期间要密切关注,减少或防止治疗相关不良反应的发生,提高治疗依从性并提高治愈率。     

异甘草酸镁治疗HIV/MTB双重感染合并ATB-DILI患者的临床研究

目的：探讨异甘草酸镁治疗艾滋病病毒/结核分枝杆菌（HIV/MTB）双重感染合并抗结核药物性肝损伤（ATB-DILI）患者的临床疗效和安全性。方法：选取2019年9月至2020年12月凉山州布拖县人民医院诊治的200例HIV/MTB双重感染合并ATB-DILI患者,随机分为观察组101例和对照组99例。观察组给予异甘草酸镁注射液100 mg,每日1次,对照组则给予还原型谷胱甘肽注射液1.2 g,每日1次,疗程均为2周。比较2组治疗后肝功能生化指标、症状和体征、临床总有效率、CD4⁺T淋巴细胞数、血清炎性指标及不良反应发生情况。结果：2组血清ALT、AST、TBIL、ALP和γ-GT水平均较治疗前有明显降低,且观察组显著低于对照组（P<0.05）。2组临床症状和体征均较治疗前有明显改善,且观察组显著优于对照组（P<0.05）。观察组临床总有效率显著高于对照组（P<0.05）。2组血清CD4⁺T淋巴细胞数水平均较治疗前有明显增加,且治疗2周后观察组显著高于对照组（P<0.05）。2组患者WBC、PCT、Hs-CRP和ESR均较治疗前有明显降低,组间比较差异无统计学意义（P>0.05）。2组患者药物不良反应发生率相仿,组间比较差异无统计学意义（P>0.05）。结论：异甘草酸镁治疗HIV/MTB双重感染合并ATB-DILI患者的临床疗效显著,不仅能明显改善临床症状和体征,还可以促进肝功能恢复,并对机体免疫重建有一定作用,且未增加不良反应发生风险。     

抗结核新药德拉马尼作用机理和化学合成的研究进展

结核分枝杆菌感染导致的结核病仍然是全球重大公共卫生威胁。耐多药结核分枝杆菌感染所致的耐多药结核病则是2035年实现终结结核病的主要障碍之一。德拉马尼是近50年来成功研发并上市的抗结核新药之一。德拉马尼主要依据抑制枝菌酸合成的酶筛选获得,但是,其具体靶标仍然有待研究。本文综述前药德拉马尼的激活途径和基因、转录组效应、作用靶标以及化学合成,为进一步精准确定其药靶提供基础。     

抗结核药物肝毒性对血浆miRNA分子表达的影响

目的探讨抗结核药物肝毒性（ATDH）对患者血浆中微RNA（miRNA）分子表达的影响。方法对3例活动性肺结核患者用药前和发生ATDH后的血浆标本进行miRNA芯片检测。对存在差异性表达的miRNA分子,采用Real Time-PCR进行验证。应用互联网miRNA靶基因预测软件对经证实存在差异性表达的miRNA进行靶基因预测,采用PANTHER蛋白分类系统查找靶蛋白基因本体（GO）功能分类。结果ATDH发生后,血浆中共筛选出22个与用药前比较差异性表达的miRNA分子,表达上凋和下调的miRNA各11个。RealTime-PCR验证结果显示：ATDH发生后,患者血浆中显著上调的miRNA有5个,分别为miR-378i、miR-125b-5P、miR-1224-5P、miR-194-5P和miR-34a-5P;下调的miRNA有3个,分别为miR-1260a、miR-338．3P和miR-4286。结论ATDH发生患者血浆中存在与用药前比较差异性表达的miRNA分子,这些分子的存在可能与ATDH的发生有关。     

慢性肾脏病合并结核感染诊治进展

慢性肾脏病（Chronic kidney disease ,CKD）和结核病是危及人类健康的慢性疾病,慢性肾脏病患者感染结核的风险增加,与CKD的进展有关,且肺外结核发生率高,临床症状不典型,结核相关筛查实验阳性率低,CKD患者抗结核药物副作用较普通人群高且严重,预后更差,早期诊断及及时治疗对改善预后有重要意义。