Remission of hepatotoxicity in chronic pulmonary aspergillosis patients after lowering trough concentration of voriconazole

BACKGROUND Chronic pulmonary aspergillosis(CPA)is a rare syndrome that is often accompanied by gradual lung tissue destruction.Voriconazole is usually employed as the first-line agent for CPA treatment.However,some patients can develop hepatotoxicity and often were forced to stop voriconazole treatment.AIM To record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of voriconazole.METHODS This study retrospectively analyzed 12 adult CPA patients who developed hepatotoxicity during the voriconazole treatment.In these patients,the oral dose was reduced to 3/4 or 1/2 of the standard dose(4 mg/kg,twice daily),and the lower limit of voriconazole trough concentration was maintained more than 0.5μg/m L.The trend of remission of liver toxicity after drug reduction in 12 patients was recorded.During the same period,25 patients who received standard doses served as the control group.Data from the two groups were collected and analyzed for different parameters such as demographic characteristics,underlying pulmonary disorders,laboratory tests,and therapeutic effect.The differences between the two groups were statistically compared.RESULTS Hepatotoxicity occurred in 12 patients within 28-65 d after oral voriconazole treatment.Hepatotoxicity was mainly manifested by the significantly increased level of gamma-glutamyltransferase and a slight increase of alanine aminotransferase and aspartate aminotransferase.The oral dose of voriconazole was reduced to approximately 3 mg/kg in seven patients and approximately 2 mg/kg in five patients.The average trough concentrations for the 12 patients before and after voriconazole oral dose reduction were 3.17±1.47μg/m L(1.5-6.0μg/m L)and 1.70±0.78μg/m L(0.6-3.3μg/m L),respectively(P=0.02).After lowering the trough concentrations,the hepatotoxicity was alleviated in all the patients.However,gamma-glutamyltransferase levels declined slowly.After 4 mo of treatment,7 of the 12 patients were successfully treated in the low trough concentrations group(41.7%).Similarly,8 of the 25 patients in the standard treatment dose group(32.0%)were effectively treated.There was no statistical difference between the groups(P=0.72).CONCLUSION Reducing the lower limit of the voriconazole trough concentration to 0.5μg/m L can alleviate the hepatotoxicity and maintained certain clinical efficacy in CPA patients;however,patients should be closely monitored.

Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis:In vitro and in vivo study

Objective:To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice.Methods:GC/MS was used for analysis of active constituents of Calotropis gigantea extract.Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus.Neutropenic mice were randomly assigned into 5 groups:group 1 was neutropenic(control);group 2 was infected with Aspergillus fumigatus;group 3 was infected with Aspergillus fumigatus,and treated with Calotropis gigantea extract;group 4 was infected with Aspergillus fumigatus and treated with amphotericin B;group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B.Fresh lung tissues were histopathologically examined.Fungal burden and gliotoxin concentration were evaluated in lung tissues.Catalase,superoxide dismutase,and malondialdehyde content were determined in lung tissues.Myeloperoxidase,tumor necrosis factor-alpha,interleukin-1,and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay.Results:Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160μg/mL,respectively,for Aspergillus fumigatus.Additionally,Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95%and inhibited production of gliotoxin in lung tissues from 6320 to 1350μg/g lung.Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation.Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced.Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated Aspergillus fumigatus and leak of cellular components after damage of the cell wall.In vivo study revealed the suppression of lung tissue damage in mice of invasive pulmonary aspergillosis,which was improved with Calotropis gigantea/amphotericin B compared to the control group.Conclusions:Calotropis gigantea/amphotericin B is a promising treatment to reduce lung fungal burden and to improve the drugs’therapeutic effect against invasive pulmonary aspergillosis.

The Effect Analysis of Different Experimental Methods for the Diagnosis of Invasive Pulmonary Aspergillosis in a Rat Model

Background: Consensus on the most reliable assays to detect invasive aspergillosis from minimally or noninvasive samples has not been reached. In this study, we compared the efficacy of an enzyme-linked immunosorbent assay (ELISA) for galactomannan (GM) detection and quantitative real-time PCR assay (qRT-PCR) for the diagnosis of invasive pulmonary aspergillosis in a rat model. Methods: Neutropenic, male Sprague-Dawley rats (specific pathogen free;8 weeks old;weight, 200 ± 20 g) were immunosuppressed with cyclophosphamide and infected with Aspergillus fumigatus intratracheally. Tissue and whole blood samples were harvested on days 1, 3, 5, and 7 post-infection and examined with GM ELISA and qRT-PCR. Results: On day 7, A. fumigatus DNA was amplified from 14 of 48 whole blood samples from immunosuppressed infected rats: day 1 (0/12), day 3 (0/12), day 5 (6/12), day 7 (8/12) post infection. The sensitivity and specificity of the qRT-PCR assay were 29.2% and 100%, respectively. Receiver operating characteristic curve (ROC) analysis indicated a Ct cut-off value of 15.35, and the area under the curve (AUC) was 0.627. The GM assay detected antigen in sera obtained on day 1 (5/12), day 3 (9/12), day 5 (12/12), and day 7 (12/12) post-infection, and thus had a sensitivity of 79.2% and a specificity of 100%. The ROC of the GM assay indicated that the optimal cut-off value was 1.40 (specificity, 100%;AUC, 0.919). Conclusions: The GM assay was more sensitive than qRT-PCR assay in diagnosing invasive pulmonary aspergillosis in rats.

A Case of Invasive Pulmonary Aspergillosis Resulted from the Treatment of Chronic Eczema

This was an advanced male(87-year-old)with refractory chronic eczema for over 40 years,based on his allergic constitution,accompanied with chronic kidney disease due to primary hypertension(CKD,phase 3).It was so difficult to tolerate the severe itching that the glucocorticoids(GC)had to be applied to it,but some new-onset respiratory symptoms,such as cough,dyspnea after exertion etc.,occurred to this patient.Some classical IPA images were found on his pulmonary CT scanning,which were further comfirmed by the positive findings of GM-test,and then a final diagno­sis of IPA was accordingly established.Unfortunately,a persistent fever emerged after starting an antifungal therapy to the patient,and his IL-2 level was detected to be superhigh.As a response to allergic fever,GC was carefully given intravenously again to treat it,and it turned out to be totally improved since then;suggesting that systemic thinking(integrated with the other clinical evidences)is essential to diagnose IPA,and GC can also be used to improve its symptoms with the existence of antifungal therapy.

111例侵袭性肺曲霉病(IPA)的临床特征及预后风险因素

目的探讨侵袭性肺曲霉病(IPA)的临床特征、实验室检查及预后风险因素。方法回顾性分析2020年9月—2023年6月某院IPA患者的临床资料,分析其临床特征及预后风险因素。结果共纳入111例IPA患者,年龄为(68.8±12.5)岁,以男性为主(63.1%),主要分布于呼吸科、重症监护病房(ICU)、血液科及感染科,共占75.6%。IPA常见的曲霉为烟曲霉、黄曲霉及黑曲霉,分别占67.6%、19.8%、4.5%。支气管肺泡灌洗液的(1,3)-β-D-葡聚糖抗原检测(G试验)、半乳甘露聚糖抗原检测(GM试验)阳性率分别为73.7%、68.0%。111例IPA患者中,32例(28.8%)随访发现预后不良,25例(22.5%)合并病毒感染。logistic多因素回归分析显示,合并病毒感染[OR(95%CI):4.535(1.385~14.846),P=0.012]、连续3周使用糖皮质激素史[OR(95%CI):9.128(2.293~36.341),P=0.002]、机械通气[OR(95%CI):4.690(1.100~19.990),P=0.037]及留置导尿管[OR(95%CI):7.144(1.345~37.950),P=0.021]是IPA患者预后不良的独立危险因素。结论多种因素与IPA预后不良有关,应联合多种检测手段早期识别并尽早给予合理治疗,以改善患者预后,同时需采取相应预防措施,避免出现医院感染。

GM试验联合肺部CT特点在诊断IPA中的应用

目的:回顾性分析血清半乳甘露聚糖(GM)实验联合肺部多层螺旋CT(MSCT)检查对诊断侵袭性肺曲霉病(IPA)的临床价值。方法:对三甲医院1963例疑似侵袭性曲霉菌感染患者的GM试验、临床资料、MSCT影像学特点进行回顾性分析。将临床抗真菌治疗成功病例作为依据,以痰培养或活组织病理学检查结果为金标准,计算敏感性和特异性。采用受试者工作特征(ROC)曲线分析血清GM试验联合MSCT影像学检查对侵袭性肺曲霉菌感染的诊断价值。结果:1963例疑似侵袭性曲霉感染患者中,GM试验阳性和阴性病例数分别为244例、1719例,对应临床诊断为IPA病例数为149例、25例;CT表现为高密度影、磨玻璃影、结节影伴或不伴空洞形成的有875例,其他CT表现的有1088例,对应诊断为IPA病例数分别是139例、35例。GM试验的敏感性、特异性是85.6%、94.7%,CT的敏感性、特异性是79.9%、59.3%,两者联合检测可分别将敏感性、特异性提高至100%(并联)、99.6%(串联)。ROC结果显示,GM试验和CT对侵袭性曲霉菌感染均有一定的诊断价值,ROC曲线下面积分别为0.902(95%CI:0.871~0.933)、0.719(95%CI:0.683~0.755),联合检测可将诊断价值进一步提高,ROC曲线下面积为0.957(95%CI:0.942~0.972)。结论:GM阳性和阴性患者影像学均可以表现高密度影、磨玻璃影或小结节影伴或不伴空洞形成等征象,所以影像学诊断IPA没有明显特异性,而本研究数据显示GM试验联合肺部CT对IPA患者的诊断价值较高,并具有重要的临床应用价值。

PA-MSHA疫苗对严重创伤患者并发肺部感染的预防作用

目的研究绿脓杆菌菌毛株(PA-MSHA)疫苗对严重创伤患者免疫功能影响和对并发肺部感染的预防作用。方法选择ICU住院严重创伤患者共55例,随机分为两组:①对照组:27例,给予常规治疗;②疫苗组:28例,除常规救治外,从入院当天给予皮下注射PA-MSHA疫苗1．0 mL,1次/d,连续注射14 d。分别在入院当天和入院第14天取静脉血测定免疫功能指标,并统计入院第14天内并发肺部感染的发生率。结果疫苗组在入院第14天时血清IgG、补体C3和C4、NK(自然杀伤细胞)活性、CD3、CD4和CD4/CD8比值均比入院当天有明显升高(P＜0．01),而对照组仅有补体C3值在入院第14天出现明显升高(P＜0．05);对照组在入院第14天内并发肺部感染发生率为44．4%,疫苗组为21．4%,疫苗组肺部感染发生率明显低于对照组(P＜0．01)。结论PA-MSHA疫苗能够明显提高严重创伤患者机体免疫功能,并且能一定程度预防肺部感染的发生率。

复方葶苈注射液对肺心病急性发作期t-PA、PAI活性的影响

目的观察复方葶苈注射液对肺心病急性发作期纤溶活性的影响。方法(1)临床观察部分:将肺心病急性发作期患者随机分为治疗组与对照组,治疗组予复方葶苈注射液,对照组予酚妥拉明,观察两组治疗后t-PA及PAI活性的变化;(2)动物实验部分:将大鼠随机分为中药组(予复方葶苈注射液)、西药组(予酚妥拉明)、模型组(予生理盐水)和空白对照组(予生理盐水),造模后分别予相应药物(空白对照组不造模),观察大鼠组织型纤溶酶原激活物(t-PA)及纤溶酶原激活物抑制物(PAI)活性的改变。结果复方葶苈注射液升高t-PA活性、降低PAI活性的作用与酚妥拉明相近。结论复方葶苈注射液可改善肺心病急性发作期患者纤溶活性。

卡泊芬净治疗恶性血液病合并IPA感染临床分析

目的:评估卡泊芬净治疗恶性血液病合并侵袭性肺曲霉菌(IPA)感染的临床疗效和安全性。方法:2008年1月-2012年12月恶性血液病合并IPA感染患者49例,所有患者均经CT检查和GM试验临床诊断;采用注射用醋酸卡泊芬净进行治疗,根据临床疗效标准,评价卡泊芬净治疗的疗效和安全性。结果:49例患者的治疗总有效率为91.84%(45/49)。卡泊芬净治疗过程中9例发生不良反应,不良反应发生率为18.37%。结论:卡泊芬净有很好的抗真菌活性,是治疗恶性血液病合并肺曲霉菌感染安全有效的药物。

自拟豁痰祛瘀方联合大剂量rt-PA溶栓治疗急性肺栓塞疗效及对其TNF-α、D-D的影响

目的观察自拟豁痰祛瘀方联合大剂量rt-PA溶栓治疗急性肺栓塞疗效及其对肿瘤坏死因子-α(TNF-α)、D-二聚体(D-D)的影响。方法选取急性肺栓塞患者共80例,以随机数字表法分为对照组和实验组各40例,分别采用大剂量rt-PA溶栓单用和与自拟豁痰祛瘀方联用治疗,比较两组临床疗效,治疗前后中医证候积分、血气分析指标、凝血指标、TNF-α及D-D水平。结果观察组临床疗效显著优于对照组(P <0.05);观察组治疗后中医证候积分显著低于对照组及本组治疗前(P <0.05);观察组治疗后氧分压(PaO2)、二氧化碳分压(PaCO2)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)水平均显著优于对照组及本组治疗前(P <0.05);同时观察组治疗后TNF-α和D-D水平均显著低于对照组及本组治疗前(P <0.05)。结论自拟豁痰祛瘀方联合大剂量rt-PA溶栓治疗急性肺栓塞能够有效缓解症状体征,改善肺通气功能和凝血功能,并有助于下调TNF-α和D-D水平。

Role of Triggering Receptor Expressed on Myeloid Cell-1 Expression in Mammalian Target of Rapamycin Modulation of CD8＋ T-cell Differentiation during the Immune Response to Invasive Pulmonary Aspergillosis

Background： Triggering receptor expressed on myeloid cell- 1 （TREM- 1） may play a vital role in mammalian target ofrapamycin （mTOR） modulation ofCD8＋ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis （IPA）. This study aimed to investigate whether the roTOR signaling pathway modulates the proliferation and differentiation of CD8＋ T-cells during the immune response to I PA and the role TREM-1 plays in this process. Methods： Cyclophosphamide （CTX） was injected intraperitoneally, and Asl？e;gillus.[mnigams spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model. After inoculation, rapamycin （2 mg-kg ·d -1） or interleukin （IL）-12 （5 μg/kg every other day） was given for 7 days. The number of CD8＋ effector memory T-cells （Tern）, expression of interferon （IFN）-y, roTOR, and ribosomal protein $6 kinase （S6K）, and the levels of IL-6, IL- 10, galactomannan （GM）, and soluble TREM- 1 （sTREM-I） were measured. Results： Viable A. fumigatus was cultured from the lung tissue of the inoculated mice. Histological examination indicated greater inflammation, hemorrhage, and lung tissue injury in both IPA and CTX ＋ IPA mice groups. The expression of mTOR and S6K was significantly increased in the CTX ＋ IPA ＋ I L- 12 group compared with the control, I PA （P = 0.01 ; P - 0.001 ）, and CTX ＋ 1PA （P = 0.034; P = 0.032） groups, but significantly decreased in the CTX ＋ IPA ＋ RAPA group （P 〈 0.001 ）. Compared with the CTX ＋ IPA group, the proportion of Tern, expression of IFN-y, and the level ofsTREM-I were significantly higher after IL-12 treatment （P = 0.024, P = 0.032, and P = 0.017, respectively）, and the opposite results were observed when the roTOR pathway was blocked by rapamycin （P 〈 0.001）. Compared with the CTX ＋ I PA and CTX ＋ I PA ＋ RAPA groups, IL-12 treatment increased IL-6 and downregulated IL- 10 as well as G M, which strengthened the immune response to the IPA infection. Conclusions： mTOR modulates CD8＋ T-cell differentiation during the immune response to IPA. TREM-1 may play a vital role in signal transduction between mTOR and the downstream immune response.

Prognostic value of serum galactomannan index in critically ill patients with chronic obstructive pulmonary disease at risk of invasive pulmonary aspergillosis

Background Critically ill chronic obstructive pulmonary disease （COPD） patients admitted to an intensive care unit （ICU） due to respiratory failure are at particularly high risk of Aspergillus infection.The serum galactomannan index （GMI） has proven to be one of the prognostic criteria for invasive pulmonary aspergillosis （IPA） in classical immunocompromised patients.However,the prognostic value of serum GMI in critically ill COPD patients needs evaluation.The purpose of this study is to investigate the prognostic value of serum GMI in patients with severe COPD.Methods In this single-center prospective cohort study,serum samples for GMI assay were collected twice a week from the first day of ICU admission to the day of the patients＇ discharge or death.Patients were divided into two groups according to their clinical outcome on the 28th day of their ICU admission.Univariate analysis and survival analysis were tested in these two groups.Results One hundred and fifty-three critically ill COPD patients were included and were divided into survival group （106 cases） and non-survival group （47 cases） according to their outcome.Univariate analysis showed that the highest GMI level during the first week after admission （GMI-high 1st week） was statistically different between the two groups.Independent prognostic factors for poor outcome in severe COPD patients were：GMI-high 1st week ＞0.5 （RR：4.04,95％ CI：2.17-7.51） combined with accumulative dosage of corticosteroids ＞216 mg before the RICU admission （RR：2.25,95％ CI：1.11-4.56） and clearance of creatinine （Ccr） ＜64.31 ml/min （RR：2.48,95％ CI：1.22-5.07）.Conclusions The positive GMI-high 1st week （＞0.5） combined with an accumulative dosage of corticosteroids ＞216 mg before the ICU admission and a low Ccr may predicate a poor outcome of critically ill COPD patients.

Initial computed tomography findings of invasive pulmonary aspergillosis in non-hematological patients

Background The computed tomography （CT） findings of invasive pulmonary aspergillosis （IPA） are unclear in non- hematological patients. The present study was a retrospective evaluation of CT images in non-hematological patients with IPA. Methods All adult patients who met the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group （EORTC/MSG） criteria for proven or probable IPA were included during a 5-year study at our institutions. Initial CT findings in our cohort were retrospectively reviewed by two independent thoracic radiologists blinded to patient demographics and clinical outcomes. The presence, pattern, and distribution of abnormalities were recorded. Results Twenty-three non-hematological patients with pathologically confirmed IPA were included in our study. Areas of ground-glass opacities were present in 14 patients （61%）, which were bilateral in 10 patients and unilateral in four. This pattern mainly involved the middle and upper lung zones. Air-space consolidation was identified in 12 patients （52%）, and the areas were distributed along the bronchus or subpleura in most cases. Other findings, including five small nodules （22%）, three macronodules （13%）, and one halo sign （4%）, were less common. Conclusions CT findings of IPA in non-hematological patients frequently manifested as acute bronchopneumonia, and ground-glass opacities and air-space consolidations were the most common CT findings of IPA in these patients.

Altered CD8＋ T-cell counts as an early predictor of prognosis in critically ill immunocompromised patients with invasive pulmonary aspergillosis

Background The number of critically ill immunocompromised （CIIC） patients has increased dramatically in recent years,and they represent a high risk population for invasive pulmonary aspergillosis （IPA） infection.Host immunity should play a major role in determining the outcome and recovery of these patients.The purpose of this study was to evaluate the dynamic changes in host immune status and its potential influence on prognosis in CIIC patients with IPA.Methods We monitored the evolution of a number of key cellular and humoral parameters on days 1,3,and 10 （D1,D3 and D10） following ICU admission in sixty-two CIIC patients with microbiological evidence of IPA.We included immunoglobulins IgG,IgA and IgM,complement factors C3 and C4,and lymphocyte subgroups CD3＋,CD4＋,CD8＋,CD28＋CD4＋,and CD28＋CD8＋ T cells,CD19＋B cells,and CD3-CD16＋CD56＋ natural killer cells （NK）.Results The primary outcome was 28-day mortality.Thirty-eight （61.3％） patients died within the 28 days following ICU admission.Compared to patients who died,CD3＋,CD8＋,CD28＋CD8＋ T-cell counts on D1,D3,and D10,CD28＋CD4＋ T-cell counts on D3 and D10,and NK counts on D3 and D10 were significantly higher in survivors.Receiver operating characteristic （ROC） analysis of immune parameters predicting 28-day mortality revealed area under the curve （AUC） values of 0.82 （95％ CI 0.71-0.92）,0.94 （95％ CI 0.87-0.99）,and 0.94 （95％ CI 0.85-0.99） for CD8＋ T-cell counts for D1,D3,and D10 respectively,and 0.84 （95％ CI 0.75-0.94）,0.92 （95％ CI 0.85-0.99）,and 0.90 （95％ CI 0.79-0.99） for CD28＋CD8＋ T-cell counts for D1,D3,and D10 respectively.Kaplan-Meier survival analysis showed that CD8＋ T-cell counts ＜149.5×106 cells/L and CD28＋CD8＋ T-cell counts ＜75×106 cells/L at ICU admission were associated with lower survival probabilities in CIIC patients with IPA （both Log rank：P＜0.001）.Conclusions Low CD8＋ and CD28＋CD8＋ T-cell counts were associated with high mortality in CIIC patients with IPA.Early counts of CD8＋ and CD28＋CD8＋ T cells in CIIC patients with IPA may be valuable for predicting outcome.

血浆BNP及PA/A预测COPD合并肺动脉高压的价值

目的探讨慢性阻塞性肺疾病(COPD)患者血浆BNP水平、PA/A对肺动脉高压的价值。方法选取在我院治疗的COPD急性加重患者93例,根据右心导管的检测分为高压组(37例)和非高压组(56例)。比较两组患者的一般资料,包括年龄、性别、BMI、吸烟史、MRC评分、合并右心衰竭比率、胸部CT的肺动脉直径和主动脉直径、血浆BNP、血浆cTnT、氧合指数、PaCO_2;应用多因素Logistic回归分析,筛选肺动脉高压的独立影响因素。作散点图,分析血浆BNP和PA/A的相关性,绘制ROC曲线,反映BNP、PA/A两者联合的诊断效能。结果 PA/A(OR=1.45)和血浆BNP(OR=1.98)是肺动脉高压的独立影响因素;血浆BNP与PA/A数值呈正相关(r=-0.553,P<0.001)。BNP和PA/A诊断肺动脉高压的最佳诊断点为1 298.425 ng/L和1.065,其敏感度为73%和64.9%,特异性为89.3%和83.9%。两者联合诊断肺动脉高压的敏感度为86.5%,特异性为82.1%。结论联合BNP或PA/A对于COPD患者肺动脉高压的诊断具有一定价值,值得在临床上合理应用。

祛痰救肺汤辅助rt-PA溶栓对急性肺栓塞的治疗效果及对凝血指标、TNF-α及D-D水平的影响

目的观察祛痰救肺汤辅助重组织型纤溶酶原激活剂(recombinant tissue-type plasminogen activator, rt-PA)溶栓对急性肺栓塞的治疗效果及对凝血指标、TNF-α及D-D水平的影响。方法选择2018年2月—2019年10月医院收治的急性肺栓塞患者97例,依据治疗方式的不同分为研究组和对照组,研究组49例,对照组48例。对照组入院后均给予氧气吸入、镇痛、检测心率、血压等常规治疗,并采用大剂量rt-PA溶栓,具体:将100 mg阿普替酶加入50 mL注射用水中,采用静脉输注,并2 h内输注完。研究组在对照组治疗的基础上,口服祛痰救肺汤治疗。两组均治疗2周。比较两组治疗前后中医症候积分和临床疗效;比较两组治疗前后PaO2、PaCO2和HR水平;比较两组治疗前后凝血功能指标PT、APTT和TT;比较两组治疗前后TNF-α和D-D水平。结果研究组治疗总有效率为87.76%(43/49)高于对照组总有效率的70.83%(34/48)(P<0.05);研究组治疗后气短、胸痛、心悸、咳嗽和疲惫乏力等中医证候积分低于对照组(P<0.05);研究组治疗后PaO2、PaCO2水平高于对照组,HR水平低于对照组(P<0.05);研究组治疗后凝血功能指标PT、APTT和TT水平高于对照组(P<0.05);研究组治疗后TNF-α和D-D水平低于对照组(P<0.05)。结论祛痰救肺汤结合rt-PA溶栓治疗急性肺栓塞疗效显著,可有效的改善患者的临床症状,纠正患者的低氧血症和血气功能,改善急性肺栓塞患者纤溶-凝血系统,减轻炎症损伤,提高治疗疗效,值得临床推广应用。

小剂量rt-PA治疗急性肺栓塞疗效分析

目的探讨小剂量重组组织型纤溶酶原激活剂(rt-PA)应用于治疗急性肺栓塞的效果。方法选择我院收治的急性肺栓塞患者60例,随机分为对照组,rt-PA组及尿激酶(UK)组,各20例,对照组采用抗凝治疗,rt-PA组采用小剂量rt-PA联合抗凝治疗,UK组采用尿激酶联合抗凝治疗,比较三组疗效、治疗时间及安全性。结果 rt-PA组与UK组的有效率及住院时间比较,差异无统计学意义(P>0.05);两组与对照组有效率及住院时间比较,差异均有统计学意义(P<0.05);三组不良反应比较,UK组多于rt-PA组及对照组,差异有统计学意义(P<0.05)。结论小剂量rt-PA治疗急性肺栓塞安全可靠。

CYP2C19 Genotyping Plus Therapeutic Drug Monitoring Dependent Voriconazole Treatment for Invasive Pulmonary Aspergillosis in a Patient with Liver Failure

Invasive pulmonary aspergillosis(IPA)is a lethal infectious disease with high mortality in patients with liver failure.Early recognition of the risk factors prompting earlier diagnosis and treatment may improve the outcomes.Voriconazole is recommended as the first-line drug for IPA,but hepatotoxicity limits its use in the context of liver diseases.We report a case of a 63-year-old female who was admitted to the Third Affiliated Hospital of Hebei Medical University due to IPA after glucocorticoid therapy for liver failure.The polymorphism of cytochrome P450(CYP)isoenzymes showed CYP2C19∗1/∗2 genotype associated with intermediate metabolism of voriconazole.However,the patient developed side effects such as skin rash,vomiting,hyperbilirubinemia,and alteration of consciousness,even if she received half of the recommended dosage for voriconazole.Therapeutic drug monitoring(TDM)was applied to guide the dosage adjustment of voriconazole in this patient,and consequently,the patient presented a favorable outcome.In conclusion,genotyping screening plus TDM dependent individualized treatment of voriconazole may improve the survival of liver failure patient with IPA.

肺动脉置管灌注r-PA治疗肺动脉栓塞的疗效观察

目的:观察重组人组织型纤溶酶原激酶衍生物(瑞通立r-PA)肺动脉灌注治疗肺动脉栓塞的疗效及安全性。方法:在数字减影血管造影(DSA)下采用瑞通立肺动脉置管灌注治疗肺动脉栓塞26例,观察处理前后肺动脉压、动脉血氧分压、收缩压变化。结果:26例患者术前肺动脉压、动脉血氧分压和收缩压分别为(64.45±7.62)、(75.38±15.87)、(86.53±12.87)mmHg;术后分别为(26.13±9.26)、(90.43±9.27)、(112.73±13.81)mmHg,治疗前后比较均有统计学差异(P<0.01)。结论:瑞通立溶栓可快速缓解肺动脉栓塞临床症状,是一种疗效肯定且安全的方法。