Application of Octenidine into Nasal Vestibules Does Not Influence SARS-CoV-2 Detection via PCR or Antigen Test Methods.

The targeted or universal decolonization of patients through octenidine for nasal treatment and antiseptic body wash for 3 to 5 days prior elective surgery has been implemented in several surgical disciplines in order to significantly reduce surgical site infections (SSIs) caused by Staphylococcus aureus carriage. However, as most healthcare facilities also screen patients on admission for pilot infection, it is imperative that a prophylactic nasal decolonization procedure not yield a false negative SARS-CoV-2 status in otherwise positive patients. We assessed the effect of a commercially available octenidine-containing nasal gel on two different screening methods-antigen (Ag) detection based on colloidal gold immunochromatography and RT-PCR-in a prospective-type accuracy pilot study in asymptomatic SARS-CoV-2-positive inpatients. All patients still showed a positive test result after using the octenidine-containing nasal gel for about 3 days; therefore, its application did not influence SARS-CoV-2 screening, which is of high clinical relevance. Of note is that Ag detection was less sensitive, regardless of the presence of octenidine. From an infection prevention perspective, these results favor octenidine-based decolonization strategies, even during seasonal SARS-CoV-2 periods. As only asymptomatic patients are considered for elective interventions, screening programs based on RT-PCR technology should be preferred.

Midterm results of the Ponseti method in the treatment of congenital clubfoot.

PURPOSE: The Ponseti method has become the gold standard for clubfoot treatment. Although promising short-term results have been published, only a few studies report results at the end of the bracing period. We aimed to evaluate the functional midterm results, rate of recurrence and need for subsequent surgery. METHODS: Patients from our prospective database of clubfeet treated with the Ponseti method with a minimum age of three years were identified. Exclusion criteria were syndrome or neurogenic association, address in a foreign country, presentation after six weeks of age, more than three casts applied elsewhere and correction with less than three casts. A total of 125 patients met the inclusion criteria. The Pediatric Outcomes Data Collection Instrument (PODCI), the disease-specific instrument (DSI) questionnaire and an invitation for a clinical examination were sent out. For patients not presenting for evaluation, data from the last follow-up were extracted. RESULTS: Seventy questionnaires (56 %) of patients with a mean age of 5.7 years (3.3-8.9 years) were returned. The DSI score (n = 65) was 85.3 (± 13.01 SD) and the PODCI score (n = 59) was 95.5 (± 6.3 SD). A total of 113 of 125 patients (90.4 %) with 182 clubfeet were examined in the study or seen in follow-up. During a mean follow-up of 5.2 years (range 3-8.5 years) a repeat tenotomy was performed in 4 % of cases, a percutaneous Achilles tendon lengthening in 3 %, a tibialis anterior tendon transfer in 13 % and open joint surgery in 5 %. The mean dorsiflexion with knee extended was 15.9° (range 0-32°; SD ± 5.5) with 16 feet (9 %) presenting less than 10°. CONCLUSIONS: The functional scores indicate that the Ponseti method results in mostly pain-free feet not limiting age-appropriate activity. In this consecutive case series open joint surgery could be avoided in 95 % of cases with a good functional and anatomic outcome.

The two-component adjuvant IC31® boosts type i interferon production of human monocyte-derived dendritic cells via ligation of endosomal TLRs.

The aim of this study was to characterize and identify the mode of action of IC31®, a two-component vaccine adjuvant. We found that IC31® was accumulated in human peripheral blood monocytes, MHC class II positive cells and monocyte-derived DCs (moDCs) but not in plasmacytoid DCs (pDCs). In the presence of IC31® the differentiation of inflammatory CD1a(+) moDCs and the secretion of chemokines, TNF-α and IL-6 cytokines was inhibited but the production of IFNß was increased. Sustained addition of IC31® to differentiating moDCs interfered with IκBα phosphorylation, while the level of phospho-IRF3 increased. We also showed that both IC31® and its KLK component exhibited a booster effect on type I IFN responses induced by the specific ligands of TLR3 or TLR7/8, whereas TLR9 ligand induces type I IFN production only in the presence of IC31® or ODN1. Furthermore, long term incubation of moDCs with IC31® caused significantly higher expression of IRF and IFN genes than a single 24 hr treatment. The adjuvant activity of IC31® on the IFN response was shown to be exerted through TLRs residing in the vesicular compartment of moDCs. Based on these results IC31® was identified as a moDC modulatory adjuvant that sets the balance of the NF-κB and IRF3 mediated signaling pathways to the production of IFNß. Thus IC31® is emerging as a potent adjuvant to increase immune responses against intracellular pathogens and cancer in future vaccination strategies.

Adjuvating the adjuvant: facilitated delivery of an immunomodulatory oligonucleotide to TLR9 by a cationic antimicrobial peptide in dendritic cells.

IC31(®) is a novel bi-component vaccine adjuvant consisting of the peptide KLKL(5)KLK (KLK) and the TLR9 agonist oligonucleotide d(IC)(13) (ODN1a). While membrane-interacting properties of KLK and immuno-modulating capabilities of ODN1a have been characterized in detail, little is known of how these two molecules function together and synergize in interacting with their primary target cells, dendritic cells (DCs). We have found that KLK-triggered aggregates entrapped ODN1a and these complexes readily associated with the DC cell surface. KLK stimulated the uptake and internalization of ODN1a via endocytosis, while the bulk of the peptide remained associated with the cell periphery. ODN1a co-localized with early and late endosomes as well as endoplasmic reticular structures. ODN1a co-localized with TLR9 positive compartments following KLK mediated uptake. These features did not depend on the expression of TLR-9. Our results reveal novel mechanisms that allow KLK to enhance the effects of the TLR-9 ligand ODN1a in immunomodulation.

Interobserver reliability of radiographic measurements of contralateral feet of pediatric patients with unilateral clubfoot.

BACKGROUND: Radiographs have traditionally been used to describe and quantify foot deformities in infants and children. We hypothesized that the interobserver reliability of measurements obtained from radiographs of pediatric feet would be low, especially with regard to the infant foot, and that normal ranges and standard deviations would decrease in association with increasing patient age. METHODS: We retrospectively reviewed 494 radiographs of 121 patients treated for unilateral clubfoot at our institution and studied the contralateral normal foot. All anteroposterior radiographs, lateral radiographs, and lateral radiographs made with the foot in maximum dorsiflexion were analyzed by three observers, and the values were recorded. The databases created by the three observers were statistically analyzed according to five predefined age groups (birth to less than three months, three months to less than twelve months, twelve months to less than three years, three years to less than seven years, and seven years to less than fourteen years). RESULTS: The anteroposterior talocalcaneal angle was rated as having good interobserver reliability (i.e., an intraclass correlation coefficient of 0.61 to 0.80) for all patients in each age group. Other angles that were associated with good interobserver reliability were the anteroposterior calcaneus-fifth metatarsal angle in the twelve months to less than three-year age group, the three-year to less than seven-year age group, and the seven-year to less than fourteen-year age group; the lateral talocalcaneal angle in the three-year to less than seven-year age group; the lateral tibiotalar angle in the three-year to less than seven-year age group; and the lateral talus-first metatarsal angle in the seven-year to less than fourteen-year age group. All other angles were rated as having very good interobserver reliability (i.e., an intraclass correlation coefficient of 0.81 to 1). The mean difference and the maximum difference among the observers decreased for all angles in nearly all age groups. CONCLUSIONS: Interobserver reliability with regard to the radiographic measurement of pediatric feet was higher than expected, although measurement discrepancies can be as great as 30° with the infant foot. Interobserver reliability tended to improve with increasing patient age. The standard deviation showed a trend toward a decrease as patient age increased, although the trend was less notable than expected.

The novel adjuvant IC31 strongly improves influenza vaccine-specific cellular and humoral immune responses in young adult and aged mice.

The compromised immune responses in the elderly as well as the threat of pandemic influenza necessitate the development of improved influenza vaccines. This study provides evidence that IC31, a two-component synthetic adjuvant signalling through TLR-9, augments humoral and cellular immune responses to seasonal influenza vaccines. Experiments performed in young adult mice showed increased HI titres and higher levels of IgG2a antibodies that were accompanied by the induction of IFN-gamma producing CD4(+) T cells after single vaccination with reduced doses of vaccine antigens, even 200 days after single immunisation. Importantly, similar effects were seen in aged mice, although most pronounced upon booster immunisation. Thus, IC31 fulfils important criteria of novel influenza vaccine adjuvants.

IC31 and IC30, novel types of vaccine adjuvant based on peptide delivery systems.

Toll-like receptor (TLR) agonists have a proven potential to become the adjuvants of the next generation when admixed and formulated with all kinds of vaccine compositions. The quality and magnitude of a vaccine-induced immune response is often strongly facilitated by TLR agonists, with the result that protection is increased and expanded toward type 1-driven immunity. DNA oligodeoxynucleotides bind to TLR9 and have been tested in a variety of vaccine settings with encouraging results. Combining oligodeoxynucleotides with poly-L-arginine (IC30) or certain artificial antimicrobial peptides dramatically improves and synergizes with the adjuvant action of TLR9 agonists, a notion that has prompted the development of IC31, an adjuvant with a promising profile in both preclinical and clinical trials.