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1.

Background

CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation.

Methods

We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4+ and CD8+ T-cells, T-regs (CD4+CD25+FoxP3+) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10).

Results

Higher initial CMV-specific CD4+ T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes.

Conclusions

This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4+ T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.  相似文献   

2.

Background

While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.

Patients and Methods

Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.

Results

The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.

Conclusion

Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease.  相似文献   

3.

Objectives

Cytomegalovirus (CMV) infections in liver transplant recipients are common and result in significant morbidity and mortality. Intravenous ganciclovir or oral valganciclovir are the standard treatment for CMV infection. The present study investigates the efficacy of oral valganciclovir in CMV infection as a preemptive treatment after liver transplantation.

Methods

Between 2012 and 2013, 161 patients underwent liver transplantation at Samsung Medical Center. All patients received tacrolimus, steroids, and mycophenolate mofetil. Patients with CMV infection were administered oral valganciclovir (VGCV) 900mg/day daily or intravenous ganciclovir (GCV) 5mg/kg twice daily as preemptive treatment. Stable liver transplant recipients received VGCV.

Results

Eighty-three patients (51.6%) received antiviral therapy as a preemptive treatment because of CMV infection. The model for end-stage liver disease (MELD) score and the proportions of Child-Pugh class C, hepatorenal syndrome, and deceased donor liver transplantation in the CMV infection group were higher than in the no CMV infection group. Sixty-one patients received GCV and 22 patients received VGCV. The MELD scores in the GCV group were higher than in the VGCV group, but there were no statistical differences in the pretransplant variables between the two groups. AST, ALT, and total bilirubin levels in the GCV group were higher than in the VGCV group when CMV infection occurred. The incidences of recurrent CMV infection in the GCV and VGCV groups were 14.8% and 4.5%, respectively (P=0.277).

Conclusion

Oral valganciclovir is feasible as a preemptive treatment for CMV infection in liver transplant recipients with stable graft function.  相似文献   

4.

Purpose of Review

Invasive candidiasis (IC) is the leading cause of fungal infections in solid organ transplant recipients (SOT). In this article, we aim to review the epidemiology, risk factors, presentation, and management of IC in this population.

Recent Findings

Certain risk factors have been associated with IC in SOT recipients. Targeted antifungal prophylaxis for SOT recipients at the highest risk of infection is currently recommended although the choice and duration of antifungal agents remain controversial. Early diagnosis and monitoring of IC in SOT recipients are critical to achieve better outcomes and prevent serious complications. Non-culture-based diagnostic modalities have been introduced to aid in earlier and more accurate diagnosis.

Summary

The use of azoles for prophylaxis or treatment in SOT recipients allowed for selection of resistance and increased the incidence of non-albicans Candida. Drug–drug interactions, cost, and risk of resistance are to be considered when using more potent or newer antifungal agents.
  相似文献   

5.
6.
Opportunistic invasive fungal infections are important infectious complications in severely immunocompromised children with hematological malignancies and/or hematopoietic stem cell transplantation, and are causes of considerable morbidity and mortality. Voriconazole is a broad-spectrum, second generation antifungal triazole with activity against yeast and filamentous fungi and first line indications against invasive aspergillosis and invasive candidiasis. While the compound has been approved in children and adolescents for several years, the dose finding in this population is ongoing and data on safety and efficacy continue to be accrued. The purpose of this article is to provide an update on the pharmacokinetics, safety and efficacy of voriconazole in pediatric patients.  相似文献   

7.
An epidemic of cytomegalovirus disease (CMV) occurred in 38 percent of 34 renal transplant recipients during an 18-month period. A characteristic clinical pattern was noted: 40 days following transplantation, daily fevers recurred for periods of four to six weeks. This fever in conjunction with a diffuse interstitial pneumonitis and impaired hepatic and renal function constituted a diagnostic tetrad. Of all the laboratory techniques, throat and urine cultures were the most consistent in confirming the diagnosis.Analysis of the epidemic implicated the communal hemodialysis unit as the source of exposure to the virus. CMV was not seen in the first 86 patients who received transplants in the program, but with increasing use of hemodialysis, the percentage of patients with positive serologic reaction for CMV increased dramatically.  相似文献   

8.
Several factors including antibiotic use, immunosuppression and frequent hospitalizations make solid organ transplant (SOT) recipients vulnerable to Clostridium difficile infection (CDI). We conducted a meta-analysis of published studies from 1991-2014 to estimate the prevalence of CDI in this patient population. We searched PubMed, EMBASE and Google Scholar databases. Among the 75,940 retrieved citations, we found 30 studies coded from 35 articles that were relevant to our study. Based on these studies, we estimated the prevalence of CDI among 21,683 patients who underwent transplantation of kidney, liver, lungs, heart, pancreas, intestine or more than one organ and stratified each study based on the type of transplanted organ, place of the study conduction, and size of patient population. The overall estimated prevalence in SOT recipients was 7.4% [95%CI, (5.6-9.5%)] and it varied based on the type of organ transplant. The prevalence was 12.7% [95%CI, (6.4%-20.9%)] among patients who underwent transplantation for more than one organ. The prevalence among other SOT recipients was: lung 10.8% [95% CI, (5.5%-17.7%)], liver 9.1 % [95%CI, (5.8%-13.2%)], intestine 8% [95% CI, (2.6%-15.9%)], heart 5.2% [95%CI, (1.8%-10.2%)], kidney 4.7% [95% CI, (2.6%-7.3%)], and pancreas 3.2% [95% CI, (0.5%-7.9%)]. Among the studies that reported relevant data, the estimated prevalence of severe CDI was 5.3% [95% CI (2.3%-9.3%)] and the overall recurrence rate was 19.7% [95% CI, (13.7%-26.6%)]. In summary, CDI is a significant complication after SOT and preventive strategies are important in order to reduce the CDI related morbidity and mortality.  相似文献   

9.

Background

The Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted.

Methodology/Principal Findings

Annual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality.

Conclusions/Significance

In this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.  相似文献   

10.
目的:研究ERCP在高年龄患者中应用的有效性和安全性。方法:回顾性分析2010年6月-2011年7月在本医院进行ER-CP诊治的患者253例。按年龄分组,其≤65岁的患者(低年组)115例,65岁-80岁的患者(中高年组)79例,≥80岁的患者(高年组)59例。记录患者ASA分级、实验室指标、ERCP操作以及并发症、住院天数情况,对结果进行统计分析。结果:253例患者进行了ERCP操作,失败8例。胆总管结石患者178例,恶性肿瘤患者48例。ERCP操作成功率为96.8%(95.6%vs 97.4%vs98.3%),取石成功率98.3%(97.3%vs 98.2%vs100%),结石取尽率96.6%(96%vs 96.5%vs 97.8%),高年组患者ASA分级比中高年和低年组高,差异有统计学意义。术前实验指标差异无统计学意义。186例接受了乳头括约肌切开(EST),(71.3%vs 73.4%vs78.0%),33例患者采用了预切开术(16.5%%vs 6.3%vs15.3%),27例患者术中出现困难插管(13.0%vs 7.59%vs10.2%),ERCP诊断胆总管结石70.4%(65.2%vs 72.2%vs78.0%),以上差异均无统计学意义,恶性肿瘤19.0%,多见于高年组患者(12.2%vs 21.5%vs28.8%),低年组和高年组差异有统计学意义,十二指肠乳头周围憩室39.9%(28.7%vs 48.1%vs50.8%),低年组分别与中高和高年组差异有统计学意义。三组患者行ERCP后病情缓解天数分别为1.61±0.83,1.39±0.72,1.49±0.70。各种并发症共43例(17.0%),低年组25例(21.7%),中高年组8例(10.1%),高年组10例(16.9%),无严重并发症及死亡发生。差异均无统计学意义。结论:1.高年组患者ASA分级较高,但ERCP操作成功率、并发症发生率及治疗后病情缓解天数与其他组患者无差别,ERCP在老年患者中的应用是安全而有效的。2.中高年组及高年组十二指肠乳头周围憩室比低年组多见,但对ERCP操作成功率和并发症发生率无影响。  相似文献   

11.
Spain has one of the world’s largest pools of organ donors and is a global leader in terms of the number of transplants it performs. The current outbreak of leishmaniasis in Fuenlabrada (in the southwest of the region of Madrid, Spain) has involved 600 clinical cases since late 2009 (prevalence 0.2%). It may therefore be wise to monitor the town’s transplanted population for Leishmania infantum; its members are immunosuppressed and at greater risk of infection and relapse following treatment. The present work examines the use of cytokine release assays to determine the prevalence of Leishmania infection in this population, and to confirm recovery following treatment for visceral leishmaniasis (VL). The humoral and cellular immune responses to L. infantum were characterized in 63 solid organ transplant (SOT) recipients from Fuenlabrada, 57 of whom reported no previous episode of VL (NVL subjects), and six of whom had been cured of VL (CVL subjects). Seventeen subjects (12 NVL and 5 CVL) showed a patent lymphoproliferative response to soluble Leishmania antigen (SLA). Stimulation of peripheral blood mononuclear cell cultures and of whole blood with SLA led to the production of different combinations of cytokines that might serve to confirm Leishmania infection or recovery from VL and help prevent cured patients from relapsing into this serious condition.  相似文献   

12.

Background

Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients.

Methods

A retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence.

Results

XDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p = 0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p = 0.01; odds ratio = 7.88 [95% CI: 1.60–38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p = 0.03).

Conclusions

XDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.  相似文献   

13.
14.

Introduction

Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group.

Objective

We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis.

Result

CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%–97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%–97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%–99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women.

Conclusion

CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.  相似文献   

15.
目的:通过对器官移植术后受者外周血中巨细胞病毒(CMV)早期抗原pp65和晚期抗原pp67-mRNA的监测,评价其对于诊断器官移植术后CMV感染、发病及预后的价值,为临床准确有效地分析理解检测结果提供依据。方法:收集28例器官移植受者EDTA抗凝外周血标本共120份,用免疫荧光技术(IFA)检测其中CMV早期抗原pp65;用核酸基础序列扩增法(NASBA)测定晚期CMVpp67-mRNA,绘制2组用于诊断CMV的受试者特征曲线(ROC曲线),比较2组曲线下面积。结果1120份样本中,42份为CMVpp65阳性(≥1个阳性细胞/2×105白细胞),23份为CMVpp67-mRNA阳性。28例器官移植受者中,9例CMVpp65和pp67-mRNA均为阳性(其中3例pp65和pp67-mRNA在同一时间为阳性),8例pp65为阳性而pp67-mRNA为阴性,2例pp65为阴性而pp67-mRNA为阳性。临床诊断感染CMV的患者4例,在感染早期无临床症状病毒潜伏期间,受试者工作特征(ROC)曲线下面积(AUC)pp65为0.9542,pp67-mRNA为0.6611,即pp65检测的灵敏度和特异性高于pp67-mRNA;而在出现临床症状并治疗后期,pp65的AUC为0.8300,pp67-mRNA为0.9232,pp67-mRNA的灵敏度和特异性高于pp65。根据ROC曲线查得,以每2x105白细胞中有10个阳性细胞为诊断CMV活动性感染的最佳临界值。结论:AUC结果表明,pp65、pp67-mRNA均具有诊断意义。pp65检测更适于早期CMV活动性诊断,对于提示临床开始抗病毒治疗具有早期快速的意义;pp67-mRNA检测快速、结果准确,可作为结束抗病毒治疗的参考指标;两者联合检测用于监测CMV,对于辅助临床诊断有很好的价值。  相似文献   

16.
Insomnia, defined as difficulty in falling asleep and/or staying asleep, short sleep duration, or poor quality sleep, is a common sleep disorder affecting 30-40% of adult population. We have conducted a randomized, double-blind, placebo-controlled study to test if anesthesia is therapeutically beneficial in patients with refractory chronic primary insomnia. We have assessed the efficacy and safety of propofol-induced sleep in these patients. This study comprised of 103 patients with refractory chronic primary insomnia (including 59 non-pregnant, non-lactating women; 28-60 years) and the participants were randomized to receive either physiological saline (placebo) (n = 39) or 3.0 g/l propofol (n = 64) in a 2-h continuous intravenous infusion for five consecutive nights. The Leeds Sleep Evaluation Questionnaire was used for the subjective assessment of sleep, and polysomnography was used for the objective measurement of sleep architecture and patterns. The assessments were done prior to and at the end of the 5-day treatment and 6 months after treatment period. The adverse effects of the treatment were also recorded. A 2-h continuous intravenous infusion of 3.0 g/l propofol for five consecutive nights improved the subjective and objective assessments of sleep in 64 patients with refractory chronic primary insomnia. This improvement occurred immediately after the therapy and persisted for 6 months. No serious adverse events were noticed during the period of drug administration or 6 months after the treatment. Propofol therapy is an efficacious and safe choice for restoring normal sleep in patients with refractory chronic primary insomnia.  相似文献   

17.
BackgroundAcute lymphoblastic leukemia (ALL) is more common in children than in adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported. However, only one study has demonstrated SNs in adult ALL. Because of the poorer survival of adult ALL, the incidence might be underestimated.ObjectiveTo evaluate the incidence and risk factors of secondary solid organ neoplasms among adult and child ALL patients.MethodsNewly diagnosed ALL patients between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent or combined malignancies were excluded. Standardized incidence ratios (SIRs) were analyzed to compare the risk of our cohort to general population in the same age, sex and calendar year. Risk factors for SN development were analyzed by Cox proportional hazards models. Effects of treatments were treated as time-dependent variables.ResultsThe 15-year cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL patients, respectively. The SIR was significantly increased in child ALL (SIR 6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14, 2.24, .87 and .71 at ≥ 10 years, 5–10 years, 1–5 years and 0–1, respectively. Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type. Multivariate analysis showed that age ≥ 20 years (hazard ratio [HR] 5.04), end-stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent risk factors for cancer development.ConclusionsWhen compared with the general population, child ALL shows a increased risk of developing SNs. CNS tumors are the most common type, and cranial irradiation is an independent risk factor. With longer follow-up, the risk of SNs increases. Hence, physicians need to pay more attention on the risk of developing SNs in long-term ALL survivors with risk factors.  相似文献   

18.

Background

Posttraumatic pseudoaneurysms (PAs) have been recognized as the cause of delayed hemorrhage complicated with nonoperative management (NOM), although the need for intervention in patients with small-sized PAs and the relationship between the occurrence of PAs and bed-rest has been also unclear.

Objectives

The purpose of this study was to investigate the clinical history of small-sized PAs (less than 10 mm in diameter) which occurred in abdominal solid organs, and to analyze the relationship between the occurrence of PAs and early mobilization from bed.

Methods

Sixty-two patients who were successfully managed with NOM were investigated. Mobilization within three days post-injury was defined as “early mobilization” and bed-rest lasting over three days was defined as “late mobilization.” A comparison of the clinical factors, including the duration of bed-rest between patients with and without PAs detected by follow-up CT was performed. Furthermore, a multiple logistic regression model analysis on the occurrence of PAs was performed.

Results

PAs were detected in 7 of the 62 patients. The One patient with PAs measuring larger than 10 mm received trans-arterial embolization, and the remaining six patients with PAs smaller than 10 mm were managed conservatively. Consequently, no delayed hemorrhage occurred, and the PAs spontaneously disappeared in all of the six patients managed without intervention. The multiple regression model analysis revealed that early mobilization was not a significant factor predicting new-onset PAs.

Conclusions

Small PAs can be expected to disappear spontaneously. Moreover, early mobilization is not a significant risk factor for the occurrence of PAs.  相似文献   

19.
20.
目的:观察不同剂量辛伐他汀治疗老年高血脂患者疗效与安全性。方法:将纳入研究的80例老年高血脂患者随机分为高剂量组和低剂量组,各40例。高剂量组给予辛伐他汀剂40 mg/日,低剂量组给予20 mg/日。治疗2个月后观察疗效、血脂水平变化情况,并统计两组不良反应的发生情况。结果:高剂量组总有效率95%显著高于低剂量组的80%(P0.05);治疗后,两组TG、TC、LDL-C、HDL-C水平均有改善,与本组治疗前比较均有显著性差异(P均0.05),且高剂量组上述指标改善明显优于低剂量组(P均0.05);治疗期间两组不良反应发生率无统计学意义(P0.05)。结论:辛伐他汀高剂量(40 mg/日)治疗老年高血脂的疗效优于低剂量(20 mg/日),且不增加不良反应发生的风险。  相似文献   

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