Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

OBJECTIVES Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. METHODS Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) ≥0.4) and occurrence of IAC during a 4-week period. RESULTS Within 4 weeks after inclusion a CCI ≥0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1, -2, -3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI ≥0.4. Similarly, none of the analyzed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p = 0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. CONCLUSION Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.

Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection

During a two-stage revision for prosthetic joint infections (PJI), joint aspirations, open tissue sampling and serum inflammatory markers are performed before re-implantation to exclude ongoing silent infection. We investigated the performance of these diagnostic procedures on the risk of recurrence of PJI among asymptomatic patients undergoing a two-stage revision. A total of 62 PJI were found in 58 patients. All patients had intra-operative surgical exploration during re-implantation, and 48 of them had intra-operative microbiological swabs. Additionally, 18 joint aspirations and one open biopsy were performed before second-stage reimplantation. Recurrence or persistence of PJI occurred in 12 cases with a mean delay of 218 days after re-implantation, but only four pre- or intraoperative invasive joint samples had grown a pathogen in cultures. In at least seven recurrent PJIs (58%), patients had a normal C-reactive protein (CRP, < 10 mg/l) level before re-implantation. The sensitivity, specificity, positive predictive and negative predictive values of pre-operative invasive joint aspiration and CRP for the prediction of PJI recurrence was 0.58, 0.88, 0.5, 0.84 and 0.17, 0.81, 0.13, 0.86, respectively. As a conclusion, pre-operative joint aspiration, intraoperative bacterial sampling, surgical exploration and serum inflammatory markers are poor predictors of PJI recurrence. The onset of reinfection usually occurs far later than reimplantation.

Characterization of the porcine transferrin gene (TF) and its association with disease severity following an experimental Actinobacillus pleuropneumoniae infection

Transferrin (TF)-mediated provision of iron is essential for a productive infection by many bacterial pathogens, and iron-depletion of TF is a first line defence against bacterial infections. Therefore, the transferrin (TF) gene can be considered a candidate gene for disease resistance. We obtained the complete DNA sequence of the porcine TF gene, which spans 40 kb and contains 17 exons. We identified polymorphisms on a panel of 10 different pig breeds. Comparative intra- and interbreed sequence analysis revealed 62 polymorphisms in the TF gene including one microsatellite. Ten polymorphisms were located in the coding sequence of the TF gene. Four SNPs (c.902A>T, c.980G>A, c.1417A>G, c.1810A>C) were predicted to cause amino acid exchanges (p.Lys301Ile, p.Arg327Lys, p.Lys473Glu, p.Asn604His). We performed association analyses using six selected TF markers and 116 pigs experimentally infected with Actinobacillus pleuropneumoniae serotype 7. The analysis showed breed-specific TF allele frequencies. In German Landrace, we found evidence for a possible association of the severity of A. pleuropneumoniae infection with TF genotypes.

Intraperitoneal and intra-nasal vaccination of mice with three distinct recombinant Neospora caninum antigens results in differential effects with regard to protection against experimental challenge with Neospora caninum tachyzoites

Recombinant NcPDI(recNcPDI), NcROP2(recNcROP2), and NcMAG1(recNcMAG1) were expressed in Escherichia coli and purified, and evaluated as potential vaccine candidates by employing the C57Bl/6 mouse cerebral infection model. Intraperitoneal application of these proteins suspended in saponin adjuvants lead to protection against disease in 50% and 70% of mice vaccinated with recNcMAG1 and recNcROP2, respectively, while only 20% of mice vaccinated with recNcPDI remained without clinical signs. In contrast, a 90% protection rate was achieved following intra-nasal vaccination with recNcPDI emulsified in cholera toxin. Only 1 mouse vaccinated intra-nasally with recNcMAG1 survived the challenge infection, and protection achieved with intra-nasally applied recNcROP2 was at 60%. Determination of cerebral parasite burdens by real-time PCR showed that these were significantly reduced only in recNcROP2-vaccinated animals (following intraperitoneal and intra-nasal application) and in recNcPDI-vaccinated mice (intra-nasal application only). Quantification of viable tachyzoites in brain tissue of intra-nasally vaccinated mice showed that immunization with recNcPDI resulted in significantly decreased numbers of live parasites. These data show that, besides the nature of the antigen, the protective effect of vaccination also depends largely on the route of antigen delivery. In the case of recNcPDI, the intra-nasal route provides a platform to generate a highly protective immune response.

Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study

The CIAO Study ("Complicated Intra-Abdominal infection Observational" Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4-98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Limited open reduction and internal fixation of displaced intra-articular fractures of the calcaneum

The extended lateral L-shaped approach for the treatment of displaced intra-articular fractures of the calcaneum may be complicated by wound infection, haematoma, dehiscence and injury to the sural nerve. In an effort to reduce the risk of problems with wound healing a technique was developed that combined open reduction and fixation of the joint fragments and of the anterior process with percutaneous reduction and screw fixation of the tuberosity. A group of 24 patients with unilateral isolated closed Sanders type II and III fractures was treated using this technique and compared to a similar group of 26 patients managed by the extended approach and lateral plating. The operation was significantly shorter (p < 0.001) in the first group, but more minor secondary procedures and removal of heel screws were necessary. There were no wound complications in this group, whereas four minor complications occurred in the second group. The accuracy and maintenance of reduction, and ultimate function were equivalent.

Intra-abdominal pressure development after different temporary abdominal closure techniques in a porcine model

BACKGROUND: Decompressive laparotomy followed by temporary abdominal closure (TAC) is an established prophylaxis and treatment for abdominal compartment syndrome. The herein presented study aimed at the comparison of volume reserve capacity and development of intra-abdominal hypertension after forced primary abdominal closure and different TAC techniques in a porcine model. METHODS: Eight anesthesized and mechanically ventilated domestic pigs underwent a standardized midline laparotomy. A bag was placed into the abdominal cavity. Before abdominal closure, the bag was prefilled with 3,000 mL water to simulate increased intra-abdominal volume. The intra-abdominal pressure (IAP) was then increased in 2 mm Hg steps up to 30 mm Hg by adding volume (volume reserve capacity) to the intra-abdominal bag. Volume reserve capacity with the corresponding IAP were analyzed and compared for primary abdominal closure, bag silo closure, a zipper system, and vacuum-assisted closure (VAC) with different negative pressures (-50, -100, and -150 mm Hg). Hemodynamic and pulmonary parameters were monitored throughout the experiment. RESULTS: Volume reserve capacity was the highest for bag silo closure followed by the zipper system and VAC with primary abdominal closure providing the least volume reserve capacity in the whole IAP range. Of interest, VAC -50 mm Hg resulted in a lower volume reserve capacity when compared with VAC -100 and -150 mm Hg. Pulmonary and hemodynamic parameters demonstrated no significant differences between primary abdominal closure and the evaluated TAC techniques at all IAP levels. CONCLUSIONS: The present experimental in vivo study indicates that bag silo closure and zipper systems may be favorable TAC techniques after decompressive laparotomy. In contrast, the VAC techniques resulted in lower volume reserve capacity and therefore may bear an increased risk for recurrent intra-abdominal hypertension in the initial phase after decompressive laparotomy.

Listeria monocytogenes spreads within the brain by actin-based intra-axonal migration

Listeria monocytogenes rhombencephalitis is a severe progressive disease despite a swift intrathecal immune response. Based on previous observations, we hypothesized that the disease progresses by intra-axonal spread within the central nervous system. To test this hypothesis, neuroanatomical mapping of lesions, immunofluorescence analysis, and electron microscopy were performed on brains of ruminants with naturally occurring rhombencephalitis. In addition, infection assays were performed in bovine brain cell cultures. Mapping of lesions revealed a consistent pattern with a preferential affection of certain nuclear areas and white matter tracts, indicating that Listeria monocytogenes spreads intra-axonally within the brain along interneuronal connections. These results were supported by immunofluorescence and ultrastructural data localizing Listeria monocytogenes inside axons and dendrites associated with networks of fibrillary structures consistent with actin tails. In vitro infection assays confirmed that bacteria were moving within axon-like processes by employing their actin tail machinery. Remarkably, in vivo, neutrophils invaded the axonal space and the axon itself, apparently by moving between split myelin lamellae of intact myelin sheaths. This intra-axonal invasion of neutrophils was associated with various stages of axonal degeneration and bacterial phagocytosis. Paradoxically, the ensuing adaxonal microabscesses appeared to provide new bacterial replication sites, thus supporting further bacterial spread. In conclusion, intra-axonal bacterial migration and possibly also the innate immune response play an important role in the intracerebral spread of the agent and hence the progression of listeric rhombencephalitis.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.