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1.
Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non-albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration ≤ 8 μ/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-5.0, P = 0.01], a Model for End-Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1-7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains. Liver Transpl, 2012. ? 2012 AASLD.  相似文献   

2.
Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had /=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.  相似文献   

3.
INTRODUCTION: Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. PATIENTS AND METHODS: Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23-65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7-10 days). RESULTS: One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. CONCLUSION: In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.  相似文献   

4.
Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.  相似文献   

5.
Use of various induction regimens, of novel immunosuppressive agents, and of newer prophylactic strategies continues to change the pattern of infections among solid organ transplant (SOT) recipients. Although invasive fungal infections (IFIs) occur at a lower incidence than bacterial and viral infections in this population, they remain a major cause of morbidity and mortality worldwide. In March 2008, a panel of Italian experts on fungal infections and organ transplantation convened in Castel Gandolfo (Rome) to develop consensus guidelines for the diagnosis, prevention, and treatment of IFIs among SOT recipients. We discussed the definitions, microbiological and radiological diagnoses, prophylaxis, empirical treatment, and therapy of established disease. Throughout the consensus document, recommendations as clinical guidelines were rated according to the standard scoring system of the Infectious Diseases Society of America and the United Stated Public Health Service.  相似文献   

6.
The aim of this study was the evaluation of the safety of anidulafungin in adult solid organ transplantation (SOT) recipients. During the study period (14 months), we included all consecutive SOT recipients from 14 centers who received anidulafungin for at least 48 hours for the treatment of invasive fungal infections (IFIs) or as prophylaxis. Relevant clinical and analytical information on clinical charts was reviewed. Clinical side effects, liver function tests, and serum creatinine levels were assessed at least weekly. The need for the modification of immunosuppressive drugs was also recorded by the investigators. All patients were followed for at least 1 week after the end of treatment (EOT) or until death. Eighty-six SOT recipients were evaluated (56 transplant recipients, 20 lung transplant recipients, 8 kidney transplant recipients, and 2 heart transplant recipients). Sixty-two patients (72%) received anidulafungin for prophylaxis, and 24 (28%) received anidulafungin for the treatment of IFIs [candidemia/invasive candidiasis (16) or invasive aspergillosis (8)]. At the baseline, only 5% of the patients were neutropenic (<500 neutrophils/mL). There was no need for the modification of immunosuppressive drug doses because of anidulafungin therapy. No patient discontinued anidulafungin because of severe adverse effects. While receiving anidulafungin, 1 patient developed mild liver toxicity, but the liver function normalized without the discontinuation of anidulafungin. At EOT, the median serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels were significantly lower than the baseline levels, even in liver transplant recipients and patients who had higher baseline levels of serum creatinine. In conclusion, these results show that anidulafungin is a well-tolerated drug in SOT recipients.  相似文献   

7.

Background

Fungal infections, although less frequent than bacterial infections, represent a severe comorbidity with an exponential increase in mortality rate in liver transplantation patients. The incidence of invasive fungal infections (IFIs) after solid organ transplantation ranges from 7% to 42%, with Candida spp. and Aspergillus spp. as the most common pathogens. Fungal infections in liver transplant recipients have been associated with poor outcome and mortality rates ranging from 65% to 90% for invasive aspergillosis and 30% to 50% for invasive candidiasis. The results largely depend on early diagnosis and early initiation of specific treatment for IFIs. Therefore, the diagnosis must be prompt, preferably based on microbiological data, both cultures and biomarkers, and/or based on clinical features and known risk factors.

Materials and Methods

This study evaluated the incidence of fungal infections in patients after liver transplantation in our center between January 2003 and December 2012. The retrospective analysis of 215 consecutive liver transplantation patients was undertaken to estimate incidence, risk factors, and clinical courses of IFIs in the first 3 months after liver transplantation.

Results

Candidemia and invasive candidiasis microbiologically proven were found in 26 patients (12%), whereas in 6 patients (2.8%) invasive fungal infections from other non-Candida fungi developed: Aspergillus (4 cases: 2 A fumigatus, 2 A terreus), Fusarium oxysporum (1 case), and Rhodotorula rubra (1 case). Two patients with Aspergillus and the patient with Fusarium died. The patient with Rhodotorula as well as 22 of the patients with candidemia (85%) survived. All of the episodes developed during the first 3 months posttransplantation. All cases have followed a previous polymicrobial bacterial infection (especially in the biliary tract) with large use of combined antibiotic therapies.

Conclusions

The rate of fungal infection was found to increase in parallel with the number of risk factors. Prophylactic strategies can decrease the risk of fungal infections. Early detection and treatment with adequate early empiric therapy is the key to obtaining a better outcome in liver transplantation patients.  相似文献   

8.

Background

In recent years the incidence of invasive fungal infections (IFIs) in post liver transplant (LT) has reduced to about 5%, however the majority of IFIs develops early in the post-transplant course. Candida species are the most frequent causative pathogens followed by Aspergillus species. Mortality for invasive candidiasis is still 40–50%. For this reason universal prophylaxis is still considered useful and is adopted by different LT centers, although it is not justified by available data. The aim of study is to evaluate Candida infection incidence and mortality in low risk patients and therefore not subjected to antifungal prophylaxis in the immediate post-LT.

Methods

The patient is defined low risk if without any risk factor for IFIs as reported in literature and according to our center protocol described below. We analyzed retrospectively the records (with 90 days follow-up) of all adult patients underwent to LT at our center in 2011–2012.

Results

At our center between 2011 and 2012, 247 LT in 232 adult patients were performed: 137 patients (59%) received prophylaxis with Amphotericin B lipid complex or liposomal Amphotericin B, 95 patients (41%) didn't receive any prophylaxis. In these latter patients was observed only one case of Candida oesophagitis at the second month post-LT. The incidence of invasive candidiasis was 0%, and there wasn't mortality ascribed to Candida infection.

Conclusions

It is possible to identify low risk patients for IFIs post-LT and the no prophylaxis policy in the early LT course appears safe and feasible.  相似文献   

9.
Clinical spectrum of fungal infections after orthotopic liver transplantation   总被引:14,自引:0,他引:14  
During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.  相似文献   

10.
Invasive fungal infections are a significant cause of morbidity and mortality for patients undergoing solid organ transplantation. Our aim was to evaluate the incidence of invasive fungal infections in solid organ recipients within a dedicated intensive care unit (ICU). MATERIALS AND METHODS: From May 2002 to May 2005, 278 patients undergoing solid organ transplantation (105 liver, 142 kidney, 20 lung, 2 combined liver-kidney, 9 combined pancreas-kidney) were admitted to our posttransplant intensive care unit. We retrospectively analyzed data obtained from the ICU stay. Fungal infection was defined by positivity of normally sterile biological samples and by elevated positivity of normally non sterile biological samples. We did not consider superficial fungal infections and asymptomatic colonizations. RESULTS: Forty-six patients (16.5%) developed a fungal infection; at least one mycotic agent was isolated from each patient. Candida albicans was the most common pathogen, isolated from 71 % of infected patients (33 of 46). Infected patients showed a mortality rate of 35%, while that for non infected recipients was 3.5%. Total length of ICU stay was the most significant risk factor among infected patients (30.26 days vs 5.04 days P < .0001). Mean time between transplantation and first positive samples was 6.17 days (SD 8.88). CONCLUSION: Fungal infections in solid organ transplant patients are a major issue because of their associated morbidity and mortality. Candida albicans was the most common pathogen and total length of ICU stay was the most important risk factor.  相似文献   

11.
BACKGROUND: Posttransplant renal replacement therapy has been shown to be an independently significant risk factor for invasive fungal infections after liver transplantation. We assessed the efficacy of a lipid preparation of amphotericin B as prophylaxis for invasive fungal infections, directed toward liver transplant recipients requiring renal replacement therapy. METHODS: A total of 148 patients transplanted between 1990 and 1997 received no antifungal prophylaxis. Since 1997, 38 patients underwent liver transplantation; antifungal prophylaxis with a lipid preparation of amphotericin B was used in patients requiring renal replacement therapy. RESULTS: Fifteen percent (22 of 148) of the patients transplanted before 1997 required renal replacement therapy. In this cohort, the incidence of invasive fungal infections (36% vs. 7%, P=0.0007) and invasive aspergillosis (14% vs. 2%, P=0.02) was significantly higher in patients who required renal replacement therapy compared with those who did not. Since 1997, 29% (11 of 38) of the patients required renal replacement therapy and received antifungal prophylaxis. Invasive fungal infections occurred in 36% (8 of 22) of the patients who received no prophylaxis (patients before 1997), and 0% (0 of 11, P=0.03) in those who received antifungal prophylaxis (since 1997). Antifungal prophylaxis was independently associated with protection from fungal infection (P=0.017). No reduction in mortality with antifungal prophylaxis was documented. CONCLUSION: Prophylaxis with a lipid preparation of amphotericin B was associated with a significant reduction in invasive fungal infections in high-risk liver transplant recipients, i.e., those requiring renal replacement therapy. However, no beneficial effect on survival could be documented.  相似文献   

12.
Viral and fungal infections in liver transplant recipients are important to recognize and treat early because of their association with substantial morbidity and mortality. Some viruses, such as cytomegalovirus and human herpesvirus 6, have immunomodulatory properties and can facilitate other infections, including fungal infections. Cytomegalovirus has long been recognized as an important virus in transplantation, but in the past decade other viruses have also received attention in the medical literature because of their association with particular clinical syndromes. Although human herpesvirus 6 has been associated with fever, rash, and encephalitis, a direct cause-and-effect relationship is still lacking. Human herpesvirus 8 has been found to be the cause of Kaposi sarcoma. Molecular techniques (e.g., pp65 antigenemia and polymerase chain reaction) that have been introduced for routine diagnosis of viruses have facilitated the diagnosis of asymptomatic viral infections and the institution of preemptive therapy. Nonetheless, the diagnosis of invasive fungal infections in liver transplant recipients is often delayed and thus associated with high mortality. Despite the use of new antifungal agents in clinical practice and the reduced incidence of fungal infections because of antifungal prophylaxis regimens, mortality has not decreased. Future patient outcomes may improve with early identification of patients who have risk factors for invasive fungal infections and with the development of new molecular diagnostic techniques for early detection.  相似文献   

13.
Fungal infections in ICU patients: epidemiology and the role of diagnostics   总被引:1,自引:0,他引:1  
Invasive fungal infections (IFIs) are on the increase not only among oncology and transplant patients but also among patients admitted to intensive care units (ICU). The rise in ICU IFIs can be attributed to the growing use of complex surgical procedures, invasive medical devices, and long-term, broad-spectrum antibiotic therapy. The majority of these life-threatening infections are caused by the well-known opportunistic pathogens Candida albicans and Aspergillus fumigatus, but new opportunistic pathogens, including yeast-like and other filamentous fungi, have emerged as additional causes. Invasive Candida infections, particularly candidemia, represent the most common IFI in critically ill patients. The species that cause candidemia markedly differ in their responses to antifungal drugs; for this reason, therapy must be tailored to the susceptibility characteristics of the infectious agent. Candidemia caused by non-albicans Candida species is increasing worldwide, and these infections are generally associated with high mortality rates, particularly bloodstream infections caused by C. krusei, which is innately resistant to fluconazole, or C. glabrata, which easily develops azole resistance. Although invasive yeast infections can be considered the most important causes of morbidity and mortality in ICU patients, pulmonary aspergillosis has recently emerged as an additional complication. Diagnosis of IFIs can be achieved using conventional approaches (microscopy, culture, and serology) and newer methods, including antigen detection and polymerase chain reaction (PCR) assays. Because most of the conventional approaches lack sensitivity, antigen detection and PCR assays could represent a valid alternative; however, these procedures need to be standardized and evaluated in a large number of patients.  相似文献   

14.
BACKGROUND: This study determines whether the spectrum, risk factors, and outcome of invasive candidiasis in liver transplant recipients have changed. METHODS: Thirty-five consecutive liver transplant recipients with invasive candidiasis were prospectively studied in a case-controlled, multicenter study. One control was matched with the case for duration of hospitalization and the other for antibiotic use so that risk factors unique in liver transplantation could be elicited. RESULTS: In matched-pair analysis, antibiotic prophylaxis for spontaneous bacterial peritonitis (odds ratio [OR] 8.3, P=0.002), posttransplant dialysis (OR 7.6, P=0.0009), and retransplantation (OR 16.4, P=0.0018) were independently significant predictors of invasive candidiasis. Candida spp. included C. albicans in 65% of patients, C. glabrata in 21%, C. tropicalis in 9%, C. parapsilosis in 3%, and C. guilliermondii in 3%. Patients with C. albicans infections were less likely to have received antifungal prophylaxis than those with non-albicans Candida infections (13.6% vs. 50%, P=0.04). The mortality rate was 36.1% for the cases and 2.8% for the controls (OR 25.0, 95% confidence interval, 6.2-100.5, P=0.0002). Non-albicans Candida infections (P=0.04) and prior antifungal prophylaxis (P=0.05) correlated with poorer outcome in the cases. CONCLUSIONS: Our study has identified predictors for Candida infections in the current era that have implications relevant for targeting the prophylaxis toward the high-risk patients. Routine use of antifungal prophylaxis warrants concern given the emergence of non-albicans Candida spp. as significant pathogens after liver transplantation and higher mortality in patients with these infections.  相似文献   

15.
16.
Invasive fungal infections are life-threatening complications in solid-organ transplantation. Although the rate of fungal infections in transplant recipients is lower than that of other infections, the mortality rate is higher. The most frequent fungi isolated from these kinds of infections are Candida spp. and Aspergillus spp. We retrospectively evaluated the clinical and laboratory findings in eight patients who were treated for invasive aspergillosis (IA) at our center. This report describes these cases and discusses the relevant literature.  相似文献   

17.
Retransplantation is a major risk factor for invasive aspergillosis in liver transplant recipients. However, the risk for invasive aspergillosis with time elapsed since retransplantation, clinical characteristics, and outcome of patients who develop this infection after retransplantation of the liver has not been defined. Patients comprised 17 liver retransplant recipients with invasive aspergillosis between 1990 and 2004. Retransplantation was considered early if it was performed within 30 days and late if performed after 30 days of the first or primary transplant. Retransplant recipients comprised 25% of all cases of invasive aspergillosis after liver transplantation. Fifty-three percent of the Aspergillus infections occurred within 30 days, and 76% within 90 days of retransplantation. In all, 53% (9/17) of the patients were late retransplant recipients. Late compared to early retransplant recipients with invasive aspergillosis were more likely to have central nervous system involvement with invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late and 63% for early retransplant recipients with Aspergillus infections. In conclusion, time-varying risk for invasive aspergillosis after retransplantation has implications relevant for guiding antifungal prophylaxis. Given a greater risk for disseminated infection and poor outcome in late retransplant recipients with aspergillosis, potent and aggressive antifungal therapy should be considered upfront in these patients.  相似文献   

18.
Fungal infections in liver transplant recipients   总被引:17,自引:0,他引:17  
Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.  相似文献   

19.
Lung transplantation (LT) is now considered to be the standard therapeutic intervention in some patients with end-stage pulmonary disease. Infectious complications after LT are relatively common due to the aggressive immunosuppression used in these receptors and local host factors derived from this type of transplant. The incidence of fungal infections after LT ranges up to 30%. However, the incidence of invasive mycoses has declined over the past decade. These mycoses are associated with high overall mortality rates despite increase of the antifungal armamentarium in the last years. Candida and Aspergillus spp produce most of these infections, but unusual moulds such as Scedosporium spp are increasingly recognized as opportunistic pathogens in LT. This review highlights the changing spectrum of invasive fungal infections, risk factors, antifungal prophylaxis, diagnosis, and treatment after LT.  相似文献   

20.
The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon‐γ (IFN‐γ) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN‐γ injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN‐γ immunotherapy was seen and no IFI relapsed during long‐term follow‐up. Our experience is both uncontrolled and in patients with unpredictable fungal infection‐related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN‐γ immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group.  相似文献   

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