Influence of tracheostomy on the incidence of catheter-related bloodstream infection in the catheterization of jugular vein by posterior access

There are no data about the influence of tracheostomy in the incidence of catheter-related bloodstream infection (CRBSI) on the catheterization of the jugular vein by posterior access and there are no recommendations relating to this circumstance in the guidelines of the Centers for Disease Control and Prevention (CDC) and of Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) for the prevention of CRBSI. The novel finding of this observational study was that there was a higher incidence of CRBSI in the catheterization of jugular vein by posterior access in patients with tracheostomy than without it (13.24 vs 0 episodes of CRBSI per 1,000 catheter-day; odds ratio = 23.92; 95% CI = 1.86-infinite; p = 0.008). Thus, the presence of tracheostomy is a risk factor of CRBSI on the catheterization of jugular vein by posterior access.     

Lower catheter-related bloodstream infection in arterial than in venous femoral catheter

In previous studies no differences were found in catheter-related bloodstream infection (CRBSI) between arterial and venous catheters. However, the distribution of each venous and arterial site could influence the results as in some studies a higher CRBSI incidence in venous and arterial femoral accesses has been found than in other venous and arterial accesses. Possibly, to eliminate this confounding, it might be more appropriate to compare the CRBSI incidence between arterial and venous catheters in the same site as the femoral access. Thus, the objective of this study was to compare the incidence of CRBSI between 618 arterial and 288 venous femoral accesses. We found higher CRBSI incidence in venous than in arterial femoral catheters (8.34 vs 1.92 CRBSI episodes/1,000 catheter-days; P < 0.001). Exact logistic regression analysis showed that venous femoral catheters had a higher risk of CRBSI than arterial femoral catheters (OR = 1.02; 95%CI =1.01-infinite; P < 0.001) controlled by APACHE-II score and duration of the catheter. The novel finding of our study is that the risk of CRBSI was higher in venous than in arterial femoral catheters. Thus, special approaches to prevent CRBSI might play a more important role in venous than in arterial catheters.     

Lower incidence of catheter-related bloodstream infection in subclavian venous access in the presence of tracheostomy than in femoral venous access: prospective observational study

Guidelines for the prevention of catheter-related bloodstream infection (CRBSI) recommend subclavian rather than femoral venous access to minimize the risk of CRBSI. However, they do not address the issue of CRBSI with subclavian venous access in the presence of tracheostomy, where the incidence of CRBSI has been found to be higher than without tracheostomy. In this study, we found lower CRBSI in subclavian venous access in the presence of tracheostomy than in femoral venous access (3.9 vs. 10.1 CRBSI per 1000 catheter-days; odds ratio = 0.39; 95% confidence interval ≤0.001–0.91; p 0.03).     

Reduction in catheter-related bloodstream infections in critically ill patients through a multiple system intervention

In this study, we aimed to determine the utility of a multiple system intervention to reduce catheter-related bloodstream infections (CR-BSI) in our intensive care unit (ICU). A prospective cohort study was undertaken in the medical and surgical ICU at a university hospital. We applied five measures: educational sessions about inserting and maintaining central venous catheters, skin cleaning with chlorhexidine, a checklist during catheter insertion, subclavian vein insertion and avoiding femoral insertion whenever possible, and removing unnecessary catheters. We determined the rate of CR-BSI per 1,000 catheter-days during the intervention (March to December 2007) and compared it with the rate during the same period in 2006 in which we applied only conventional preventive measures. CR-BSI was defined as the recovery of the same organism (same species, same antibiotic susceptibility profile) from catheter tip and blood cultures. We registered 4,289 patient-days and 3,572 catheter-days in the control period and 4,174 patient-days and 3,296 catheter-days in the intervention period. No significant differences in the number of patients with central venous catheters during the two periods were observed: catheters were used in 81.5% of patients during the control period and in 80.6% of patients during the intervention period. During the control period, 24 CR-BSI were diagnosed (6.7/1,000 catheter-days); during the intervention period, 8 CR-BSI were diagnosed (2.4/1,000 catheter-days) (relative risk 0.36; 95% confidence interval [CI] 0.16 to 0.80; p = 0.015). Nurses interrupted the procedure to correct at least one aspect when completing the checklist in 17.7% of insertions. In conclusion, a multiple system intervention applying evidence-based measures reduced the incidence of CR-BSI in our ICU.     

Catheter-related bacteremia from femoral and central internal jugular venous access

The objective of this prospective observational study was to determine the influence of femoral and central internal jugular venous catheters on the incidence of catheter-related bacteremia (CRB). We included patients admitted to a 12-bed polyvalent medico-surgical intensive care unit over 4 years who received one or more femoral or central internal jugular venous catheters. We diagnosed 16 cases of CRB in 208 femoral catheters and 22 in 515 central internal jugular venous catheters. We found a higher incidence of CRB with femoral (9.52 per 1,000 catheter days) than with central internal jugular venous access (4.83 per 1,000 catheter days; risk ratio = 1.93; 95% confidence interval: 1.03-3.73; P = 0.04). Central internal jugular venous access could be considered a safer route of venous access than femoral access in minimizing the risk of central venous catheter-related bacteremia.     

CD24 expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression

Expression of the mucin-like adhesion molecule CD24 has been implicated in the progression of several types of cancer and has been identified as new prognostic factor. We evaluated CD24 expression in 268 consecutive cases of upper urinary tract urothelial carcinoma with respect to associations with tumour stage, grade, angioinvasion and infiltrative growth pattern using a tissue microarray technique and correlated data with patient outcome. CD24 expression was demonstrated in 161/259 (62%) evaluable tumours and was associated with high tumour stage [77/139 (55%) pTa/pT1 vs 84/120 (70%) pT2–pT4; P = 0.02] and high tumour grade [68/139 (49%) low vs 93/120 (78%) high grade; P < 0.001] as well as presence of angioinvasion (P = 0.002) and infiltrative pattern of invasion (P = 0.007). Patients with CD24-positive tumours tended to have a higher risk of disease progression (P = 0.065). Multivariate analysis, however, proved pT stage >1 [P < 0.001, risk ratio (RR) = 5.87, 95% confidence interval (CI) = 2.88–11.95] and high tumour grade (P < 0.001, RR = 3.30, 95% CI 1.75–6.22) as only independent predictors of metastatic disease. In conclusion, CD24 expression in upper urinary tract urothelial cancer is associated with advanced tumour stage and high tumour grade as well as histopathological features indicative of aggressive tumour behaviour, but it lacks independent impact on patient outcome.     

Rifampicin–miconazole-impregnated catheters save cost in jugular venous sites with tracheostomy

Antimicrobial-impregnated catheters are more expensive than standard catheters (S-C). A higher incidence of catheter-related bloodstream infection (CRBSI) has been found in jugular venous access with tracheostomy than without tracheostomy. The objective of this study was to determine central venous catheter (CVC)-related costs (considering only the cost of the CVC, diagnosis of CRBSI, and antimicrobial agents used to treat CRBSI) using rifampicin-miconazole-impregnated catheters (RM-C) or S-C in jugular venous access with tracheostomy. We performed a retrospective cohort study of patients admitted to the intensive care unit (ICU) with tracheostomy who received one or more jugular venous catheters. RM-C showed a lower incidence of CRBSI compared with S-C (0 vs. 20.16 CRBSI episodes/1,000 catheter-days; odds ratio=0.05; 95% confidence interval=0.001-0.32; p<0.001) and lower CVC-related costs (including the cost of the CVC, diagnosis, and treatment of CRBSI) (11.46 ± 6.25 vs. 38.11 ± 77.25; p<0.001) in jugular venous access with tracheostomy. The use of RM-C could reduce CVC-related costs in jugular venous access with tracheostomy. The results of our study may contribute to clinical decision-making and selection of those patients who could benefit from the use of antimicrobial-impregnated catheters.     

Prognostic value of procalcitonin in <Emphasis Type="Italic">Legionella</Emphasis> pneumonia

The diagnostic reliability and prognostic implications of procalcitonin (PCT) (ng/ml) on admission in patients with community-acquired pneumonia (CAP) due to Legionella pneumophila are unknown. We retrospectively analysed PCT values in 29 patients with microbiologically proven Legionella-CAP admitted to the University Hospital Basel, Switzerland, between 2002 and 2007 and compared them to other markers of infection, namely, C-reactive protein (CRP) (mg/l) and leukocyte count (10⁹/l), and two prognostic severity assessment scores (PSI and CURB65). Laboratory analysis demonstrated that PCT values on admission were >0.1 in over 93%, >0.25 in over 86%, and >0.5 in over 82% of patients with Legionella-CAP. Patients with adverse medical outcomes (59%, n = 17) including need for ICU admission (55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly higher median PCT values on admission (4.27 [IQR 2.46–9.48] vs 0.97 [IQR 0.29–2.44], p = 0.01), while the PSI (124 [IQR 81–147] vs 94 [IQR 75–116], p = 0.19), the CURB65 (2 [IQR 1–2] vs 1 [1–3], p = 0.47), CRP values (282 [IQR 218–343], p = 0.28 vs 201 [IQR 147–279], p = 0.28), and leukocyte counts (12 [IQR 10–21] vs 12 [IQR 9–15], p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a higher prognostic accuracy to predict adverse outcomes (AUC 0.78 [95%CI 0.61–96]) as compared to the PSI (0.64 [95%CI 0.43–0.86], p = 0.23), the CURB65 (0.58 [95%CI 0.36–0.79], p = 0.21), CRP (0.61 [95%CI 0.39–0.84], p = 0.19), and leukocyte count (0.57 [95%CI 0.35–0.78], p = 0.12). Kaplan-Meier curves demonstrated that patients with initial PCT values above the optimal cut-off of 1.5 had a significantly higher risk of death and/or ICU admission (log rank p = 0.003) during the hospital stay. In patients with CAP due to Legionella, PCT levels on admission might be an interesting predictor for adverse medical outcomes. Jeannine Haeuptle, Roya Zaborsky, and Rico Fiumefreddo contributed equally to this article.     

Compliance with recommendations and clinical outcomes for formal and informal infectious disease specialist consultations

The purpose of this study was to compare compliance with recommendations and clinical outcomes between formal and informal infectious disease specialist consultations. Six hundred twenty-seven consecutive adult inpatients who received an infectious disease consultation in a university-affiliated hospital were included. After adjusting for quintile of propensity score, we compared compliance with the consultant’s recommendations and clinical outcomes for 443 (70.7%) and 184 (29.3%) formal and informal consultations. Informal and formal consultations were associated with comparable levels of compliance with recommendations for antimicrobial treatment (86.5% vs 88.9%; adjusted odds ratio [aOR], 0.63; 95% confidence interval, 0.34–1.14; P = 0.13) and diagnostic or monitoring tests (72.6% vs 72.0%; aOR, 0.91 [0.53–1.57]; P = 0.73). The rates of early clinical improvement (58.2% vs 58.6%; aOR, 1.11 [0.70–1.74]; P = 0.66), subsequent consultation (34.2% vs 36.3%; aOR, 0.80 [0.53–1.21]; P = 0.29), in-hospital mortality (4.9% vs 8.4%; aOR, 0.55 [0.24–1.24]; P = 0.15), and the median length of stay (23 vs 20 days; aOR of discharge, 0.90 [0.74–1.10]; P = 0.30) did not differ depending on the type of consultation. This study provides observational evidence that informal consultations result in levels of compliance with recommendations comparable to formal consultations, without compromising patient safety. Further study is needed to refine the criteria for requesting or providing informal rather than formal consultations.     

<Emphasis Type="Italic">Aspergillus</Emphasis> infection in lung transplant patients: incidence and prognosis

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992–2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01–1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14–3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.     

Rotation of antimicrobial therapy in the intensive care unit: impact on incidence of ventilator-associated pneumonia caused by antibiotic-resistant Gram-negative bacteria

The development of antibiotic resistance is associated with high morbidity and mortality, particularly in the intensive care unit (ICU) setting. We evaluated the effect of an antibiotic rotation programme on the incidence of ventilator-associated pneumonia (VAP) caused by antibiotic-resistant Gram-negative bacteria. We conducted a 2-year before-and-after study at two medical–surgical ICUs at two different tertiary referral hospitals. We included all mechanically ventilated patients admitted for ≥48 h who developed VAP. From 1 January through 31 December 2007, a quarterly rotation of antibiotics (piperacillin/tazobactam, fluoroquinolones, carbapenems and cefepime/ceftazidime) for the empirical treatment of VAP was implemented. We analysed the incidence of VAP and the antibiotic resistance patterns of the responsible pathogens in 2006, before (P1) and, in 2007, after (P2) the introduction of the scheduled rotation programme. Overall, there were 79 VAP episodes in P1 and 44 in P2; the mean incidence of VAP was 20.96 cases per 1,000 days of mechanical ventilation (MV) during P1 and 14.97 in P2, with no significant difference between periods on segmented regression analysis. We observed a non-significant reduction of the number of both the poly-microbial (14 [17.7%] in P1 and 5 [10.6%] in P2 [p = 0.32]) and of the antibiotic-resistant Gram-negative bacteria-related VAP (42 [45.2%] in P1 and 16 [34%] in P2 [p = 0.21]). Conversely, the number of VAP caused by Pseudomonas aeruginosa passed from 8.35 per 1,000 days of MV in P1 to 2.33 per 1,000 days of MV in P2 (p = 0.02). No difference in ICU mortality and crude in-hospital mortality between P1 and P2 was noted. Moreover, no significant change of microbial flora isolated through clinical cultures was observed. We were able to conclude that, despite global microbial flora not being affected by such a programme, antibiotic therapy rotation may reduce the incidence of VAP caused by antibiotic-resistant Gram-negative bacteria in the ICU, such as Pseudomonas aeruginosa. The application of this programme may also improve antibiotic susceptibility. However, further studies are needed to confirm our results.     

Impact of multi-drug-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> on clinical outcomes

We conducted a retrospective matched cohort study to examine the impact of isolation of multi-drug-resistant (MDR) Acinetobacter baumannii on patient outcomes. Cases from whom MDR A. baumannii was isolated in a clinical culture (n = 118) were compared with controls from whom MDR A. baumannii was not isolated (n = 118). Cases and controls were matched according to ward, calendar month of hospitalization, and duration of hospitalization before culture. The following outcomes were compared in multivariable analysis: in-hospital mortality, length of stay, need for mechanical ventilation, and functional status at discharge. MDR A. baumannii was determined to be a pathogen in 72% of cases. In 36% of cases, the patient died, versus 21% of controls (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.17–4.16, P = 0.014). Median length of stay for surviving cases was 17 days, versus 11 for surviving controls (multiplicative effect 1.55, 95% CI 0.99–2.44, P = 0.057). Fifty-two percent of cases required mechanical ventilation, versus 25% of controls (OR 3.72, 95% CI 1.91–7.25, P<0.001); 60% of surviving cases were discharged with reduced functional status, versus 38% of controls (OR 4.4, 95% CI 1.66–11.61, P = 0.003). In multivariable analysis, clinical isolation of MDR A. baumannii remained a significant predictor of mortality (OR 6.23, 95% CI 1.31–29.5, P = 0.021), need for mechanical ventilation (OR 7.34, 95% CI 2.24–24.0, P<0.001), and reduced functional status on discharge (OR 7.93, 95% CI 1.1–56.85, P = 0.039). Thus, MDR A. baumannii acquisition is associated with severe adverse outcomes, including increased mortality, need for mechanical ventilation, and reduced functional status.     

Incidence and risk factors for newly acquired hepatitis C virus infection among Aboriginal versus non-Aboriginal Canadians in six regions, 1999–2004

The purpose of this study was to compare hepatitis C virus (HCV) incidence and recent patterns of transmission within Aboriginal and non-Aboriginal Canadians. Cases of newly acquired HCV infection (in patients ≥15 years) reported to the Enhanced Hepatitis Strain Surveillance System from six jurisdictions in Canada were analyzed. Information on demographic and clinical characteristics as well as risk factors for HCV infection was collected using standardized questionnaires. Univariate analysis showed Aboriginal patients to be significantly more likely than non-Aboriginal patients to report injection drug use (77.1% vs. 64.0%; p < 0.05), to be female (54.6% vs. 37.6%; p < 0.05), to report high-risk sexual behaviors (48.6% vs. 34.1%, p < 0.05), and to report drug snorting (45.7% vs. 32.7%, p < 0.05). The median age of Aboriginal patients was significantly younger than that of non-Aboriginal patients (31 years [range, 15–71] vs. 34 years [range, 15–81]; p < 0.05). The overall incidence of HCV infection per 100,000 people aged 15 years and older was 18.9 (95% confidence interval [CI] 15.5–23.1) in Aboriginal people and 2.8 (95%CI 2.6–3.1) in non-Aboriginal people. Poisson regression analysis revealed that Aboriginal Canadians were more likely than non-Aboriginal Canadians to develop acute hepatitis C (adjusted rate ratio 5.8, 95%CI 4.7–7.3). An appropriate and effective public health strategy that includes planned and implemented prevention programs in partnership with the Aboriginal community is needed.     

Fungal colonization and/or infection in non-neutropenic critically ill patients: results of the EPCAN observational study

The purpose of this paper is to determine the incidence of fungal colonization and infection in non-neutropenic critically ill patients and to identify factors favoring infection by Candida spp. A total of 1,655 consecutive patients (>18 years of age) admitted for ≥7 days to 73 medical-surgical Spanish intensive care units (ICUs) participated in an observational prospective cohort study. Surveillance samples were obtained once a week. One or more fungi were isolated in different samples in 59.2% of patients, 94.2% of which were Candida spp. There were 864 (52.2%) patients with Candida spp. colonization and 92 (5.5%) with proven Candida infection. In the logistic regression analysis risk factors independently associated with Candida spp. infection were sepsis (odds ratio [OR] = 8.29, 95% confidence interval [CI] 5.07–13.6), multifocal colonization (OR = 3.49, 95% CI 1.74–7.00), surgery (OR = 2.04, 95% CI 1.27–3.30), and the use of total parenteral nutrition (OR = 4.37, 95% CI 2.16–8.33). Patients with Candida spp. infection showed significantly higher in-hospital and intra-ICU mortality rates than those colonized or non-colonized non-infected (P < 0.001). Fungal colonization, mainly due to Candida spp., was documented in nearly 60% of non-neutropenic critically ill patients admitted to the ICU for more than 7 days. Proven candidal infection was diagnosed in 5.5% of cases. Risk factors independently associated with Candida spp. infection were sepsis, multifocal colonization, surgery, and the use of total parenteral nutrition.     

Influence of complete spinal cord injury on skeletal muscle mechanics within the first 6 months of injury

In this study we examined the influence of complete spinal cord injury (SCI) on the mechanical characteristics of skeletal muscle in vivo within 6 months of the injury. Surface electrical stimulation (ES) was applied to the left m. quadriceps femoris of patients at 6, 11 and 24 weeks after injury. Surface ES was also applied to seven able-bodied controls (AB) at two time points 18 weeks apart. ES consisted of 2 bouts of 20, 1-s isometric contractions with 2 s and 2 min of rest between contractions and bouts, respectively. The time from 20–80% of peak torque (rise time) and the half relaxation time (1/2 RT) were determined for the first and for the last few contractions. Force loss over repeat contractions was greater in SCI than AB (27% vs 95%; P = 0.0001), and did not change over the 18-week period. Rise time did not change over repeat contractions, was not different between groups, and nor did it change over the 18-week period (range: 150–172 ms). 1/2 RT showed several group differences. Overall, 1/2 RT was longer at the beginning of ES in SCI than AB [mean (SE) 133 (15) ms vs 90 (6) ms, P = 0.037]. Slowing of relaxation time with force loss over repeat contractions was found in SCI at 24 weeks after injury [167 (18) ms, P = 0.016], but not at 6 [128 (14) ms] or 11 [145 (12) ms] weeks after injury. AB, in contrast, showed prolonged relaxation times, with force loss at both time points [115 (10) ms and 113 (11) ms; P = 0.0001]. The results indicate that SCI alters the relaxation but not contractile properties of mixed skeletal muscle within the first 24 weeks of injury. Altered calcium handling and contraction-induced fiber injury are suggested to explain the slower relaxation time per se, and the prolonged relaxation with force loss observed after SCI. Accepted: 19 July 1999     

Analysis of Risk Factors for Ventilator-Associated Pneumonia in a Multidisciplinary Intensive Care Unit

 A prospective study was conducted to determine the incidence, risk factors and pathogens of ventilator-associated pneumonia (VAP) in 198 patients requiring mechanical ventilation for more than 48 hours. VAP occurred in 67 (33.8%) patients. Risk factors associated with VAP were admission APACHE II score >20 (odds ratio [OR] 4.77, 95% confidence interval [CI] 2.04–11.27, P<0.001), mechanical ventilation >10 days (OR 44.4, 95% CI 2.16–26.7, P<0.0001), ICU length of stay >10 days (OR 9.4, 95% CI 3.55–25.65, P<0.0001), and admission PaO₂/FiO₂ ratio <200 mmHg (OR 3.4, 95% CI 1.00–11.41, P<0.05). Logistic regression analysis showed a relationship between VAP and length of stay in ICU, duration of fever and presence of catheter-related infection. The pathogens isolated were predominantly gram-negative bacteria (83.2%), with a high proportion of Acinetobacter spp. (35%) resistant to commonly used antimicrobial agents. The mortality rate was not influenced by VAP.     

Infections in Renal Transplant Recipients Receiving Mycophenolate Versus Azathioprine-Based Immunosuppression

Differences in the incidence, etiology, type, and outcome of infections occurring during the first 6 months after transplantation were evaluated in two consecutive cohorts of kidney recipients who received immunosuppressive regimens based on either azathioprine (plus antilymphocyte globulin, cyclosporine A, and prednisone) (ATG-AZA cohort) or mycophenolate-mofetil (plus cyclosporine A and prednisone) (MMF cohort). The overall incidence of infections in the two cohorts was similar (0.99±1.06 infections/patient in the MMF cohort and 1.04±0.99 in the ATG-AZA cohort, P=0.3), as was the incidence of bacterial and fungal infections. In patients who received mycophenolate, cytomegalovirus disease occurred at a higher incidence (0.3±0.54 vs. 0.1±0.34 episodes/patient, P=0.005) and affected the upper gastrointestinal tract more frequently (0.21±0.48 vs. 0.025±0.16 episodes of cytomegalovirus ulcerative esophagitis, gastritis, or duodenitis per patient; P=0.001). A nonsignificant trend toward a higher recipient survival for patients receiving mycophenolate was noted (100% vs. 95%, P=0.07). In multivariate analysis, the following factors were independently associated with a higher risk of cytomegalovirus disease: the serostatus R–/D+ (seronegative recipients who received a kidney from a seropositive donor) (RR=35.7 [95%CI, 7.4–166.7]), treatment with mycophenolate (RR=10.4 [95%CI, 2.7–38.4]), and the development of any episodes of acute rejection (RR=10.1 [95%CI, 2.5–41.6]). These data show that kidney recipients receiving mycophenolate have a higher incidence of cytomegalovirus disease, mainly affecting the upper gastrointestinal tract, compared to those receiving azathioprine-based immunosuppression. Electronic Publication     

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of case–control observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using “Epstein-Barr virus” and “multiple sclerosis” as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 3.37–8.81; p < 0.0001), anti-complex EBNA IgG (OR = 5.4; 95% CI = 2.94–9.76; p < 0.0001) and anti-EBNA-1 IgG (OR = 12.1; 95% CI = 3.13–46.89; p < 0.0001). No significant association could be found when studying anti-EA IgG (OR = 1.3; 95% CI = 0.68–2.35; p = 0.457), EBV DNA in serum (OR = 1.8; 95% CI = 0.99–3.36; p = 0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR = 0.9; 95% CI = 0.38–2.01; p = 0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anti-complex EBNA and anti-VCA IgG.     

LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma

Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan–Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62–87%] versus 60% [95% CI: 32–80%], p = 0.062) and EFS (74% [95% CI: 58–85%] versus 43% [95% CI: 15–69%], p = 0.070) and LI with OS (71% [95% CI: 57–81%] versus 56% [95% CI: 26–78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.