Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection.

OBJECTIVES: There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection. METHODS: We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality. RESULTS: Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p < 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p < 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p < 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%). CONCLUSIONS: Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/µl or neutrophils <1,000/µl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Limited impact of cytomegalovirus infection in the long-term outcome of renal and liver transplant.

BACKGROUND: The strength of the assumed association of CMV and long term deleterious events in solid organ transplant recipients (SOT) is controversial. OBJECTIVES: The aim of the present study was to evaluate whether viral replication dynamics during CMV infection or CMV disease may correlate not only with graft dysfunction and survival, but also with other potentially related late events in a long-term followed cohort of kidney (KT) and liver (LT) transplant recipients. STUDY DESIGN: 162 SOT (104 kidney, 58 liver) at our institution (2003-2005) with survival over 180 days and a median follow-up of 71 months (9-86) were analyzed. Using a Cox proportional hazard model, CMV infection (including area under the curve of DNAemia[AUC]) and CMV disease in the first 180 days were evaluated as potential predictors of the following late events (>180 days): mortality, graft dysfunction (GD), graft loss (GL), cardiovascular events (CVE), malignant tumors (MT). RESULTS: CMV infection occurred in 59% and CMV disease in 8%. Late death occurred in 17%, GD in 45.6%, GL in 14.2%, CVE in 10.5% and MT in 9.9%. We found no significant association between the intensity or duration of CMV viremia (AUC, persistent viremia or untreated CMV viremia) or CMV disease and the development of evaluated late events. According multivariate analysis neither CMV infection (hazard ratio [HR] 2.18 95% CI 0.949-5 p = 0.066) nor CMV disease (HR: 1.72; 95% CI 0.59-5 p = 0.31) were significantly correlated with late mortality. CONCLUSIONS: Our data do not support that CMV infection or CMV disease contribute significantly to long-term deleterious events in SOT.

Preemptive therapy is not adequate for prevention of cytomegalovirus disease in pancreas-kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains the most common viral infection after pancreas-kidney transplantation (PKT). Comparative studies about CMV prophylaxis in PKT have not been developed. METHODS: We analyzed CMV disease in a cohort of 84 PKT recipients. All received intravenous ganciclovir during treatment with anti-thymocyte globulin and later one of the following options for pre-transplant CMV-seropositive recipients: (a) no prophylaxis (n=10 patients), (b) preemptive therapy (PT) (n=13), or (c) continuous prophylaxis (CP) for 12 weeks (n=29). Pre-transplant CMV-seronegative recipients received CP (n=21). RESULTS: Eleven patients were excluded because of organ explantation in the first 15 days. Incidence of CMV disease in seropositive recipients was 30% under no prophylaxis, 23% under PT, and 6.9% under CP. Incidence of CMV disease under CP was 33.3% in seronegative recipients. Six of 9 episodes of CMV disease under CP occurred after finishing prophylaxis. Under CP, the incidence of CMV disease was significantly higher in seronegative than in seropositive recipients (P<0.05). CONCLUSION: According to the results of our study, for CMV-seropositive PKT recipients, CP is a better strategy than PT. For CMV-seronegative recipients, 3 months of CP is an inadequate strategy.

Efficacy and safety of valgancyclovir as preemptive therapy for the prevention of cytomegalovirus disease in solid organ transplant recipients.

We prospectively followed 70 CMV-seropositive solid organ transplant recipients to evaluate the efficacy and safety of valganciclovir (VGCV) as preemptive therapy based on antigenemia test to prevent cytomegalovirus (CMV) disease. From December 2003 to May 2004, 12 of 70 (17%) asymptomatic patients who showed an antigenemia value > or =25 positive cells per 2 x 10(5) polymorphonuclear (PMN) were treated with VGCV (900 mg twice a day adjusted to renal function) until resolution of CMV antigenemia, a minimum of 14 days. No patient developed CMV disease during follow-up. Only one who showed an asymptomatic relapse of the antigenemia test > or =25 positive cells was successfully treated with a repeated course of VGCV. Mean duration of VGCV therapy was 18 days (range, 14 to 28). Antigenemia was negative in 7 of 12 (58%) patients after 14 days and negative in all patients 4 weeks after the administration of VGCV. No significant side effects were associated with the use of VGCV therapy. Preemptive VGCV therapy is safe and effective in the prevention of CMV disease in seropositive solid organ transplant recipients.

Incidence and clinical impact of fluoroquinolone-resistant Escherichia coli in the faecal flora of cancer patients treated with high dose chemotherapy and ciprofloxacin prophylaxis.

This study evaluated the susceptibility of Escherichia coli to quinolones in 72 stool samples collected from 31 patients with solid tumours who had undergone high dose chemotherapy (HDC) and peripheral blood stem-cell (PBSC) rescue with ciprofloxacin prophylaxis. Samples were obtained at admission, after completing prophylaxis and three months later. All E. coli strains isolated from baseline samples were susceptible to quinolones. Fluoroquinolone-resistant E. coli strains were isolated in 10 (32%) patients in the second sample. In eight of these patients isolates were susceptible 3 months later. No patient developed infection due to fluorquinolone-resistant E. coli. No differences were observed in outcome between patients with susceptible and resistant flora.