Possibility of application of new pneumococcal conjugate vaccines in children in Slovenia

The emergence of pneumococcal strains resistant to penicillin caused a lot of problems in the therapy of invasive diseases, and added new dimensions to the role of immunisation. In addition to the currently available 23-valent pneumococcal polysaccharide vaccine (PPV) and a new 7-valent conjugate vaccine (PCV) (Prevnar, Wyeth Lederle), two new conjugate vaccines—a 9- and a 11-valent—are being developed. So far, the choice of most appropriate vaccines has depended on the established prevalence of serotypes causing invasive diseases and their antibiotic resistance in the Slovene children population. Between 1993 and 2001, 263 invasive pneumococcal strains isolated from children with invasive diseases were typed. During the period 1998–2001, the same 161 invasive strains were tested for their antibiotic sensitivity. Streptococcus pneumoniae was identified as the major cause of invasive bacterial diseases in the Slovene children population, especially in children under 4 years of age. Distribution by age groups showed the highest incidence in children aged 0–1 years. The predominant serotypes in all age groups were serotypes 14, 1, 19F, 23F, 6B, 18C and 6A. The distribution of penicillin-intermediate and penicillin-resistant strains showed the predominance of serotypes 23F, 14 and 19F. As concerns infection with S. pneumoniae serotypes, we have proved that children aged less than 5 years are more likely to be infected with penicillin-nonsusceptible or intermediate susceptible strains than older children. The 7-valent conjugate vaccine covers 74% of invasive strains in toddlers, but is less effective in older children.

We can conclude that the 9-valent vaccine formulation is optimal for our country, but further cost-effectiveness analysis must be done for recommendation of wide use.

At that moment it is reasonable to use the 7-valent conjugate vaccine for children with chronic cardiovascular, pulmonary, urinary and liver diseases, with asplenia, neoplasmia, diabetes, meningomyelocoele, before or after bone marrow transplantation and in cases of immunodeficiency.     

Complex hepatobiliary surgery in the community setting: is it safe and feasible?

Background

Complex hepatobiliary surgical procedures for benign and malignant conditions are regularly performed at tertiary academic referral centers with excellent outcomes, but whether similar surgical outcomes are achievable in community hospitals is not well documented.

Methods

Eighty-four patients underwent complex hepatobiliary surgery between December 2004 and December 2008. Data were prospectively analyzed, including patient demographics, operative procedures, perioperative parameters, pathology, complications up to 30 days postoperatively, and long-term outcomes.

Results

The most frequent procedures performed were isolated segmentectomy or segmentectomies (n = 41 [49%]). Major hepatic resections (n = 32 [38%]) included 25 lobectomies (30%) and 7 trisegmentectomies (8%). Nine patients (11%) had surgical complications, and the most common indications for surgery was metastatic carcinoma (n = 42 [50%]).

Conclusions

Complex hepatobiliary surgery can be performed safely at a community-based teaching hospital with excellent outcomes. In the ongoing debate centering on mandatory referral and centralization of complex surgical procedures, tertiary community hospitals with well-determined outcomes should be included.     

Meningococcal disease in Slovenia (1993-1999): serogroups and susceptibility to antibiotics. Slovenian Meningitis Study Group

The epidemiology of meningococcal disease was studied prospectively in Slovenia from 1993 to 1999 in children and from 1995 to 1999 in adults. Patients with meningococci isolated from normally sterile body sites were included in the study. Altogether 75 patients (57 children, 18 adults) were found with meningococcal diseases. The overall yearly incidence was 0.43 per 100000 inhabitants. The highest annual incidence (18.5/100000) was found in children between 1 month and 1 year of age. The case to fatality ratio was 4.1%. Group B meningococci were isolated most frequently (84.7%), followed by group C (11.1%). In six patients (8.3%) isolates were less susceptible to penicillin. Four of these were successfully treated with penicillin alone.     

PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose

Objective and Design

Inflammation is a key component of a number of diseases, including diabetic retinopathy. We investigated the cellular pathway by which protein kinase A (PKA) inhibited high mobility group box 1 (HMGB1).

Methods

Primary human retinal endothelial cells (REC) were grown in normal glucose (5 mM) or high glucose (25 mM). Cells in high glucose were treated with exchange protein for cAMP 1 (Epac1) and IGFBP-3 siRNA. Additional cells in high glucose were treated with forskolin, a PKA agonist, and Epac1 siRNA. Some cells were treated with a plasmid for insulin-like growth factor binding protein 3 (IGFBP-3) that does not bind IGF-1. Finally, some REC received Ex527, a sirtuin 1 (SIRT1) antagonist, prior to forskolin treatment. Protein analyses were done for HMGB1, Epac1, IGFBP-3, SIRT1, and PKA.

Results

PKA inhibited cytoplasmic HMGB1, independent of Epac1 actions. PKA activated IGFBP-3 and SIRT1 to inhibit cytoplasmic HMGB1. High glucose inhibited SIRT1 levels and increased cytoplasmic HMGB1 in REC.

Conclusions

PKA requires active IGFBP-3 and SIRT1 to inhibit HMGB1 inflammatory actions in the retina vasculature. Activation of these pathways may offer new targets for therapy development.

     

Macrolide resistance rates in respiratory pathogens in Slovenia following reduced macrolide use

The aim of this study was to investigate the association between decreased use of macrolides and resistance of common respiratory pathogens in Slovenia from 1999 to 2004. Over a 6-year period the consumption of macrolides in Slovenia decreased by 21.3%, from 3.81 defined daily doses/1000 inhabitants per day (DID) to 3.0 DID. The use of short-acting, intermediate-acting and long-acting subclasses of macrolides decreased by 50%, 18% and 13%, respectively. In the same period, resistance of invasive strains of Streptococcus pneumoniae increased from 4.6% to 11.1% and resistance of non-invasive strains of S. pneumoniae and Streptococcus pyogenes increased from 12.8% to 20.2% and from 7.4% to 12.5%, respectively. Resistance increased significantly more in children than in adults (P = 0.05) and was significantly correlated with increased use of intermediate-acting macrolides (r = 0.94 for non-invasive S. pneumoniae and r = 0.96 for S. pyogenes) in children. Resistance of Haemophilus influenzae and Moraxella catarrhalis was low and did not change. In children and adults, the emergence and spread of multidrug-resistant strains of invasive S. pneumoniae was observed. The decline in total macrolide use was not paralleled by reduced macrolide resistance rates of S. pyogenes and S. pneumoniae during the 6-year period. There was a strong correlation between the use of intermediate-acting macrolides and macrolide resistance of S. pyogenes and S. pneumoniae in children. Further reduction in the use of intermediate- and long-acting macrolides should be encouraged.     

Characterisation of invasive Haemophilus influenzae isolates in Slovenia, 1993–2008

The objectives of our study were to describe the epidemiology of invasive Haemophilus influenzae disease from 1993 to 2008 in Slovenia, a country with routine H. influenzae serotype b (Hib) conjugate vaccination since the year 2000. A total of 292 isolates of H. influenzae, recovered from a normally sterile site, were collected in the study period. The isolates were serotyped by slide agglutination and antibiotic susceptibility was determined. One hundred and eight isolates received after the year 2000 were serotyped by slide agglutination and by polymerase chain reaction (PCR) capsule typing, and both methods were compared. After the introduction of the routine Hib vaccination, the incidence of H. influenzae disease in children under the age of 5 years has decreased by 87.6% and type b was replaced by non-typeable H. influenzae as the predominant serotype. The proportion of serotype b decreased from 85.3% in the pre-vaccination period to 13.0% in the vaccination period and the proportion of non-capsulated isolates increased from 12.0 to 85.2%. The study of genetic relatedness by pulsed-field gel electrophoresis (PFGE) demonstrated that the isolates of serotypes b and f were genetically homogeneous within the serotype. The results of our national surveillance showed that the vaccine has been very efficient in preventing Hib invasive disease in Slovenia. Nevertheless, we see a need for further monitoring of invasive H. influenzae infections at a national level.     

Complex Pancreatic Surgery: Safety and Feasibility in the Community Setting

Introduction  

Advances in technology, innovative surgical procedures, and enhanced perioperative care have allowed more patients to be considered for complex pancreatic surgery. Published reports on the outcomes of pancreatic surgery performed at high volume tertiary referral centers have yielded excellent results. However, similar outcome and safety data from community hospitals is limited.