Percutaneous Anorectoplasty (PARP)-An Adaptable, Minimal-Invasive Technique for Anorectal Malformation Repair

Background: Anorectal malformations comprise a broad spectrum of disease. We developed a percutaneous anorectoplasty (PARP) technique as a minimal-invasive option for repair of amenable types of lesions. Methods: Patients who underwent PARP at five institutions from 2008 through 2021 were retrospectively analyzed. Demographic information, details of the operative procedure, and perioperative complications and outcomes were collected. Results: A total of 10 patients underwent the PARP procedure during the study interval. Patients either had low perineal malformations or no appreciable fistula. Most procedures were guided by ultrasound, fluoroscopy, or endoscopy. Median age at PARP was 3 days (range 1 to 311) days;eight patients were male. Only one intraoperative complication occurred, prompting conversion to posterior sagittal anorectoplasty. Functional outcomes in most children were highly satisfactory in terms of continence and functionality. Conclusions: The PARP technique is an excellent minimal-invasive alternative for boys born with perineal fistulae, as well as patients of both sexes without fistulae. The optimal type of guidance (ultrasound, fluoroscopy, or endoscopy) depends on the anatomy of the lesion and the presence of a colostomy at the time of repair

Habitual physical activity in patients born with oesophageal atresia: a multicenter cross-sectional study and comparison to a healthy reference cohort matched for gender and age

Oesophageal atresia (EA) is associated with life-long gastrointestinal and respiratory morbidity and other associated malformations. The aim of this study is to compare physical activity (PA) levels of children and adolescents with and without EA. A validated questionnaire (MoMo-PAQ) was used to evaluate PA in EA patients EA (4–17 years), who were randomly matched for gender and age (1:5) with a representative sample of the Motorik-Modul Longitudinal Study (n = 6233). Sports activity per week (sports index) and minutes of moderate to vigorous physical activity per week (MVPA minutes) were calculated. Correlations between PA and medical factors were analysed. In total, 104 patients and 520 controls were included. Children with EA were significantly less active at higher intensities (mean MPVA minutes 462; 95% confidence interval (CI): 370–554) compared to controls (626; 95% CI: 576–676), although there was no statistically significant difference in the sports index (187; 95% CI: 156–220 versus 220; 95% CI: 203–237). A lower mean weight-for-age and height-for-age, additional urogenital (r =  − 0.20, p = 0.04) or anorectal malformation (r =  − 0.24, p = 0.01) were associated with fewer MVPA minutes. For other medical factors (prematurity, type of repair, congenital heart disease, skeletal malformation or symptom load), no statistically significant association with PA was found. Conclusion: EA patients participated in PA at a similar level but lower intensities compared to the reference cohort. PA in EA patients was largely independent of medical factors

Identification of a PA-Binding Peptide with Inhibitory Activity against Influenza A and B Virus Replication

There is an urgent need for new drugs against influenza type A and B viruses due to incomplete protection by vaccines and the emergence of resistance to current antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2 and PA subunits, represents a promising target for the development of new drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between the PB1 and PA subunits of the polymerase complex of influenza A virus using a small peptide derived from the PA-binding domain of PB1. However, this influenza A virus-derived peptide did not affect influenza B virus polymerase activity. Here we report that the PA-binding domain of the polymerase subunit PB1 of influenza A and B viruses is highly conserved and that mutual amino acid exchange shows that they cannot be functionally exchanged with each other. Based on phylogenetic analysis and a novel biochemical ELISA-based screening approach, we were able to identify an influenza A-derived peptide with a single influenza B-specific amino acid substitution which efficiently binds to PA of both virus types. This dual-binding peptide blocked the viral polymerase activity and growth of both virus types. Our findings provide proof of principle that protein-protein interaction inhibitors can be generated against influenza A and B viruses. Furthermore, this dual-binding peptide, combined with our novel screening method, is a promising platform to identify new antiviral lead compounds

Pterygium axillae as a rare manifestation of Poland syndrome

AbstractPoland syndrome is characterized by a combination of absent pectoralis muscle, abnormalities of the rib cage, the breast, as well as brachy-syndactyly. We report a case of a 3 month old girl who was born with right sided axillary pterygium combined with flattening of the right anterior chest wall. Resection of a sclerotic band with reconstruction by Z-plasty was performed. Intraoperative and histopathological findings confirmed that the axillary pterygium developed on the basis of a scarred, hypoplastic pectoralis major muscle. Our case adds to the body of evidence that Poland syndrome may present in a heterogeneous fashion, including the rare finding of axillary pterygium with associated contracture. In these cases, early intervention prevents functional impairment

Telementoring in Minimally Invasive Esophageal Atresia Repair: Results of a Case-Control Study and Lessons Learned from the TIC-PEA Study (Telemedical Interdisciplinary Care for Patients with Esophageal Atresia)

Minimally invasive esophageal atresia (EA) repair is deemed one of the most demanding procedures in pediatric surgery. Open repair is considered the gold standard and learning opportunities for minimally invasive repairs remain scarce. “Telemedical Interdisciplinary Care for Patients with Esophageal Atresia (TIC-PEA)” offers free access to an interdisciplinary network of experts for telemedical consultation (telementoring). The aim of this study was to determine the frequency of minimally invasive surgery (MIS) in TIC-PEA patients compared to the general population. TIC-PEA patients were matched and compared to controls regarding the use of MIS, patient characteristics, and complications. Patients (n = 31) were included at a mean age of 62.8 days (95%-CI: 41.4–84.3, 77% after the primary esophageal repair). The odds-ratio to have MIS was 4.03 (95%-confidence interval: 0.79–20.55) for esophageal anastomosis and 4.60 (95%-confidence interval: 0.87–24.22) for tracheoesophageal fistula-repair in the TIC-PEA group. Telementoring offered the chance to select the ideal candidate for MIS, plan the procedure, and review intraoperative images and videos with the expert. Telementoring as offered is ideal to promote MIS for EA and helps to address the individual learning curve. In order to maximize benefits, patients need to be included prior to the first esophageal procedure

Reply to Peña, A. Comment on “Küppers et al. Percutaneous Anorectoplasty (PARP)—An Adaptable, Minimal-Invasive Technique for Anorectal Malformation Repair. <i>Children</i> 2022, <i>9</i>, 587”

Thank you so much for your thoughtful comments [...

Dual-binding properties of the FluA/B peptide chimera PB1_1–25A_T6Y.

<p>(A) – (D) Binding of overexpressed HA-tagged PA subunits of differing influenza strains in cell extracts to the immobilized peptides corresponding to the domains of FluA PB1 (PB1_1–25A), FluB PB1 (PB1_1–25B) or FluA PB1 T6Y (PB1_1–25A_T6Y) was determined by ELISA. Signals using the cognate peptide and lysate were normalized to 1. Binding of the PA subunits to the control peptides was not observed (data not shown). Upper panels: Western blot of the PA-containing cell extracts used. Molecular weights shown in kilodaltons. (F) Structure of FluA PB1_1–15 (green) bound to FluA PA (grey) as published <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007517#pone.0007517-He1" target="_blank">[25]</a>. T6 forms a hydrogen bond (green line) to a water molecule (blue). Molecular modeling suggests that the aromatic side chain in the mutant T6Y (orange) fits into a hydrophobic pocket and displaces the water molecule.</p

Virus type-specific conservation of the PA-binding domain and interaction of PA with PB1.

<p>(A) Upper panel: Alignment of the N-terminal 25 aa of FluA and FluB PB1. The dotted box indicates the 3₁₀-helix comprising the core PA-binding domain of PB1. FluA-specific (blue) and FluB-specific (red) aa are highlighted. Middle and lower panels: Alignment of the N-terminal 25 aa of all available FluA and FluB sequences available in the NCBI influenza virus database. Figures on the right hand side indicate the number of sequences present in the database. Grey bars highlight aa which reconstitute the 3₁₀-helix of FluA PA and possibly of FluB PA. (B) A/SC35M- and B/Yamagata/73-derived PB1 chimeras used in (b). Note that all PB1 proteins were expressed with C-terminal HA-tags. (C) Human 293T cells were transfected with expression plasmids coding for the indicated PB1 proteins and the C-terminally hexahistidine-tagged PA of FluA (FluA-PA_His). Cell lysates were prepared 24 hours post transfection and subjected to immunoprecipitation (IP) using anti-HA (αHA) agarose. Precipitated material was separated by SDS-PAGE and analyzed by Western blot for the presence of either His- or HA-tagged polymerase subunits using appropriate antibodies. Protein expression was controlled by analyzing equal amounts of cell lysate. Molecular weights are shown in kilodaltons.</p