Congenital Heart Defects in Patients with Anorectal Malformations: A Retrospective Cohort Study of 281 Patients.

In patients born with anorectal malformations (ARM), additional congenital heart defects (CHD) can occur. We aimed to provide an overview on disease and treatment details of CHD identified in patients born with ARM, from a unique large cohort of a very rare disease. We performed a retrospective single-center cohort study between January 2000 and July 2023. All consecutive patients with ARM were included. Outcomes were the number of patients with CHD, and screening percentage and percentage of patients diagnosed with CHD over 3 time periods (2000-2006, 2007-2014, 2015-2023). We used uni- and multi-variable logistic regression analyses to search for associations between CHD present and baseline characteristics. In total, 281 patients were included. Some 241 (85.8%) underwent echocardiography, of whom 80 (33.2%) had CHD. Screening percentage with echocardiography increased (74.1% vs. 85.7% vs. 95.9%, p < 0.001) and percentage of patients diagnosed with CHD remained similar over time (30.2% vs. 34.5% vs. 34.0%, p = 0.836). Atrial and ventricular septal defects (n = 36, n = 29), and persistent left superior vena cava (n = 17) were most identified. The presence of VACTERL-association or a genetic syndrome was independently associated with the presence of CHD. CHD were present in 33% of patients with ARM that underwent echocardiography. Over time, the number of CHD identified through screening remained similar. Patients with the presence of VACTERL-association or a genetic syndrome had a higher risk of having CHD. Therefore, acknowledging the potential presence of CHD in patients with ARM remains important.

Row1, a member of a new family of conserved fungal proteins involved in infection, is required for appressoria functionality in Ustilago maydis.

The appressorium of phytopathogenic fungi is a specific structure with a crucial role in plant cuticle penetration. Pathogens with melanized appressoria break the cuticle through cell wall melanization and intracellular turgor pressure. However, in fungi with nonmelanized appressorium, the mechanisms governing cuticle penetration are poorly understood. Here we characterize Row1, a previously uncharacterized appressoria-specific protein of Ustilago maydis that localizes to membrane and secretory vesicles. Deletion of row1 decreases appressoria formation and plant penetration, thereby reducing virulence. Specifically, the Δrow1 mutant has a thicker cell wall that is more resistant to glucanase degradation. We also observed that the Δrow1 mutant has secretion defects. We show that Row1 is functionally conserved at least among Ustilaginaceae and belongs to the Row family, which consists of five other proteins that are highly conserved among Basidiomycota fungi and are involved in U. maydis virulence. We observed similarities in localization between Row1 and Row2, which is also involved in cell wall remodelling and secretion, suggesting similar molecular functions for members of this protein family. Our data suggest that Row1 could modify the chitin-glucan matrix of the fungal cell wall and may be involved in unconventional protein secretion, thereby promoting both appressoria maturation and penetration.

Identifying Preoperative Clinical Characteristics of Unexpected Gastrointestinal Perforation in Infants-A Retrospective Cohort Study.

BACKGROUND: Infants presenting with unexpected pneumoperitoneum upon abdominal X-ray, indicating a gastrointestinal perforation (GIP), have a surgical emergency with potential morbidity and mortality. Preoperative determination of the location of perforation is challenging but will aid the surgeon in optimizing the surgical strategy, as colon perforations are more challenging than small bowel perforations. Therefore, the aim of this study is to provide an overview of preoperative patient characteristics, determine the differences between the small bowel and colon, and determine underlying causes in a cohort of infants with unexpected GIP. METHODS: All infants (age ≤ 6 months) who presented at our center with unexpected pneumoperitoneum (no signs of pneumatosis before) undergoing surgery between 1996 and 2024 were retrospectively included. The differences between the location of perforation were analyzed using chi-squared and t-tests. Bonferroni correction was used to adjust for multiple tests. RESULTS: In total, 51 infants presented with unexpected pneumoperitoneum at our center, predominantly male (N = 36/51) and premature (N = 40/51). Among them, twenty-six had small bowel, twenty-two colon, and three stomach perforations. Prematurity (p = 0.001), birthweight < 1000 g (p = 0.001), respiratory support (p = 0.001), and lower median arterial pH levels (p = 0.001) were more present in patients with small bowel perforation compared with colon perforations. Pneumatosis intestinalis was more present in patients with colon perforation (p = 0.004). All patients with Hirschsprung disease and cystic fibrosis had colon perforation. The final diagnoses were mainly focal intestinal perforations (N = 27/51) and necrotizing enterocolitis (N = 9/51). CONCLUSIONS: Infants with unexpected GIP, birthweight < 1000 g, and prematurity have more risk for small bowel perforation. In case of colon perforation, additional screening (for Hirschsprung and cystic fibrosis) should be considered.

Erratum: Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

[This corrects the article DOI: 10.1055/a-2227-6389.].

Systematic review on management of high-output enterostomy in children: An urgent call for evidence.

OBJECTIVES/BACKGROUND: High-output stoma is one of the most common major morbidities in young children with an enterostomy that could lead to intestinal failure. Management of high-output enterostomy in children is mostly based on personal experience. This systematic review aims to clarify the evidence-based therapeutic approach of high-output enterostomy in children. METHODS: A systematic review was performed using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published until March 20, 2023, following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The study population comprised children (i.e., age <18 years) with high-output enterostomy (i.e., jejuno-, ileo-, and/or colostomy), regardless of underlying aetiology. Interventions comprised any (non)pharmacological and/or surgical treatment. Interventions were compared with each other, placebos, and/or no interventions. Primary outcome was reduction of enterostomy output. Secondary outcomes were morbidity, mortality, quality of life, associated healthcare costs, and adverse events. RESULTS: The literature search identified 4278 original articles of which 366 were screened on full text, revealing that none of the articles met the inclusion criteria. CONCLUSION: This first systematic review on management of high-output enterostomy in children revealed that any evidence on the primary and secondary outcomes is lacking. There is an urgent need for evidence on conservative treatment strategies including fluid restrictions, dietary advices, oral rehydration solution, chyme re-infusion, and pharmacological and surgical treatments of high-output enterostomy in children, aiming to reduce the risk for short- and long-term complications. Till more evidence is available, a systematic and multidisciplinary step-up approach is needed. Therefore, a therapeutic work-up is proposed that could guide the care.

Different Analgesia Techniques for Postoperative Pain in Children Undergoing Abdominal Surgery for Intractable Constipation: A Retrospective Cohort Study in a Single Tertiary Children's Hospital.

Functional constipation in the pediatric population is a prevalent issue that is usually well managed. However, in rare cases, conservative treatment fails, and surgical intervention is necessary. This retrospective cohort study aimed to describe and compare different perioperative analgesic techniques in children undergoing major abdominal surgery for intractable constipation. Conducted between 2011 and 2021, this study enrolled patients under 18 years old who underwent initial major abdominal surgery for intractable constipation (i.e., creation of ostomy or subtotal colectomy). Patients were categorized according to the perioperative analgesic technique (i.e., systemic, neuraxial, or truncal block). Of 65 patients, 46 (70.8%) were female, and the median age was 13.5 [8.8-16.1] years during initial major abdominal surgery. Systemic analgesia was used in 43 (66.2%), neuraxial in 17 (26.2%), and truncal blocks in 5 (7.7%) of the surgeries. Patients with neuraxial analgesia reported less postoperative pain (median [interquartile range] numeric rating scale (NRS) 2.0 [0-4.0]), compared to systemic analgesia (5.0 [2.0-7.0], p < 0.001) and to truncal blocks (5.0 [3.0-6.5], p < 0.001). In this preliminary investigation, neuraxial analgesia appears to be the most effective approach to reducing acute postoperative pain in pediatric patients undergoing major abdominal surgery for intractable functional constipation. However, well-designed studies are warranted.

Green Synthesis of Er-Doped ZnO Nanoparticles: An Investigation on the Methylene Blue, Eosin, and Ibuprofen Removal by Photodegradation.

We present a study on the green synthesis of undoped and Er-doped ZnO compounds using Mangifera indica gum (MI). A set of tests were conducted to assess the structure of the material. The tests included X-ray diffraction, Raman, and Fourier-transform infrared spectroscopy. Optical properties were studied using diffuse reflectance and photoluminescence. Morphological and textural investigations were done using SEM images and N2 adsorption/desorption. Furthermore, photocatalytic tests were performed with methylene blue (MB), yellow eosin (EY), and the pharmaceutical drug ibuprofen (IBU) under UV irradiation. The study demonstrated that replacing the stabilizing agent with Mangifera indica gum is an effective method for obtaining ZnO nanoparticles. Additionally, the energy gap of the nanoparticles exhibits a slight reduction in value. Photoluminescence studies showed the presence of zinc vacancies and other defects in both samples. In the photocatalytic test, the sample containing Er3+ exhibited a degradation of 99.7% for methylene blue, 81.2% for yellow eosin, and 52.3% for ibuprofen over 120 min. In the presence of methyl alcohol, the degradation of MB and EY dyes is 16.7% and 55.7%, respectively. This suggests that hydroxyl radicals are responsible for the direct degradation of both dyes. In addition, after the second reuse, the degradation rate for MB was 94.08%, and for EY, it was 82.35%. For the third reuse, the degradation rate for MB was 97.15%, and for EY, it was 17%. These results indicate the significant potential of the new semiconductor in environmental remediation applications from an ecological synthesis.

Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

We present the case of a patient with the rare type D esophageal atresia (EA), diagnosed after correction of an EA initially diagnosed as type C. Routine postoperative contrast esophagogram showed a missed proximal tracheoesophageal fistula. This case report illustrates the potential difficulties to diagnose type D EA.

Anatomical Gynecological Anomalies in Girls Born with Anorectal Malformations: A Retrospective Cohort Study of 128 Patients.

STUDY OBJECTIVE: In girls born with an anorectal malformation (ARM), anatomical gynecological anomalies (GA) may be present and might need treatment. Therefore, the aim of this study was to provide an overview of GA in girls born with ARM in our cohort. Additionally, diagnostic timing and methods for GA were assessed. METHODS: A retrospective mono-center study was performed from January 2000 to December 2022. All patients assigned female at birth were eligible for inclusion. GA were classified according to ESHRE/ESGE classification. Outcomes were the number of girls with GA with subsequent screening methods, factors associated with GA, and GA requiring treatment. Uni- and multivariable logistic regression analyses were performed to identify the association between baseline characteristics and the presence of GA. RESULTS: In total, 128 girls were included, of whom 30 (24.1%) had additional GA, with vaginal anomalies being present most often (n = 17). Fifty-six patients (43.8%) underwent full screening, and this number improved over time (37.7% before 2018 vs 72.7% after 2018; P = .003). Thirteen of 30 patients (43.3%) required surgical treatment for their GA, without the occurrence of postoperative complications. CONCLUSION: Additional GA were present in almost a quarter of the girls born with an ARM, with vaginal anomalies most often identified. Despite GA being most often found in patients with cloacal malformations, these anomalies were also identified in patients with other ARM types. Surgical treatment was required in almost half of the girls with GA. Therefore, this study emphasizes the importance of screening for GA in patients with an ARM, regardless of the ARM type.

Facile Synthesis of Ni-Doped ZnO Nanoparticles Using Cashew Gum: Investigation of the Structural, Optical, and Photocatalytic Properties.

This work adopted a green synthesis route using cashew tree gum as a mediating agent to obtain Ni-doped ZnO nanoparticles through the sol-gel method. Structural analysis confirmed the formation of the hexagonal wurtzite phase and distortions in the crystal lattice due to the inclusion of Ni cations, which increased the average crystallite size from 61.9 nm to 81.6 nm. These distortions resulted in the growth of point defects in the structure, which influenced the samples' optical properties, causing slight reductions in the band gaps and significant increases in the Urbach energy. The fitting of the photoluminescence spectra confirmed an increase in the concentration of zinc vacancy defects (VZn) and monovacancies (Vo) as Zn cations were replaced by Ni cations in the ZnO structure. The percentage of VZn defects for the pure compound was 11%, increasing to 40% and 47% for the samples doped with 1% and 3% of Ni cations, respectively. In contrast, the highest percentage of VO defects is recorded for the material with the lowest Ni ions concentration, comprising about 60%. The influence of dopant concentration was also reflected in the photocatalytic performance. Among the samples tested, the Zn0.99Ni0.01O compound presented the best result in MB degradation, reaching an efficiency of 98.4%. Thus, the recovered material underwent reuse tests, revealing an efficiency of 98.2% in dye degradation, confirming the stability of the photocatalyst. Furthermore, the use of different inhibitors indicated that •OH radicals are the main ones involved in removing the pollutant. This work is valuable because it presents an ecological synthesis using cashew gum, a natural polysaccharide that has been little explored in the literature.

Development of an international core outcome set for treatment trials in paediatric inguinal hernia: protocol for a three-phase study including a systematic review and Delphi survey.

INTRODUCTION: In children, open inguinal hernia repair has been the gold standard for treatment, but with recent technical advancements in laparoscopy, laparoscopic hernia repair is gaining popularity. Despite available results from comparative studies, there is still no consensus regarding the superiority of open versus laparoscopic treatment strategy. An important reason for lack of consensus is the large heterogeneity in the trials' reported outcomes and outcome definitions, which limits comparisons between studies and precludes conclusions regarding the superiority of treatment strategies. The development and implementation of a core outcome set (COS) is a solution for this heterogeneity in the selection, measurement and reporting of trial outcome measures across studies. Currently, there is no COS for the treatment of paediatric inguinal hernia. METHODS AND ANALYSIS: The aim of this project is to reach international consensus on a minimal set of outcomes that should be measured and reported in all future clinical trials investigating inguinal hernia repair in children. The development process comprises three phases. First, we identify outcome domains associated with paediatric inguinal hernia repair from a patient perspective and through a systematic review of the literature using EMBASE, MEDLINE and the Cochrane Library databases. Second, we conduct a three-step Delphi study to identify and prioritise 'core' outcomes for the eventual minimal set. In the third phase, an expert meeting is held to establish the final COS and develop implementation strategies with participants from all stakeholder groups: healthcare professionals, parents and patients' representatives. The final COS will be reported in accordance with the COS-Standards for Reporting statement. ETHICS AND DISSEMINATION: The medical research ethics committee of the Amsterdam UMC confirmed that the Dutch Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that full approval by the committee is not required. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021281422.

Trends in Simple and Complex Appendicitis in Children and the Potential Correlation to Common Viral Pathogens-A Retrospective Cohort Study between 2010 and 2019 in The Netherlands.

The aim of this study was to evaluate the annual, seasonal and monthly trends in children with simple and complex appendicitis and their correlation to common viral pathogens in the Netherlands. A consecutive multicenter retrospective cohort study was performed between 2010 and 2019 including children (<18 years) surgically treated for appendicitis. The primary outcome was the distribution of children with simple and complex appendicitis per year, season and month. Relevant seasonal variation was defined as ≥5%. The secondary outcome was a positive correlation of the number of patients with simple and complex appendicitis to common viral pathogens (data anonymously provided by the Dutch Working Group on Clinical Virology from the Dutch Society for Clinical Microbiology (NVMM)). In total, 896 patients were included: N = 524 (58%) patients with simple and N = 372 (42%) with complex appendicitis. Of the children aged 0-5 years, 81% had complex appendicitis, versus 38% in 6-18 years (p < 0.001). An overall decline was demonstrated for both simple and complex appendicitis between 2010 and 2019. No seasonal variation was found for simple appendicitis. For complex appendicitis, the highest number of patients was found in spring, and lowest in summer (N = 372, spring 28.2 ± 5.1% versus summer 21.0 ± 5.8%, p = 0.011), but the variance was regarded as not relevant (<5% from baseline). A positive correlation was found between complex appendicitis with Adenovirus 40.41 (R = 0.356, 95%CI 0.045-0.604, p = 0.026) and simple appendicitis with Adenovirus NON 40.41 (R = 0.332, 95%CI 0.019-0.586, p = 0.039), but these correlations did not remain significant after a Bonferroni correction (p < 0.003). In conclusion, we found no relevant seasonal variation for simple or complex appendicitis, nor positive correlation with common viral pathogens.

Potential benefits of routine cystoscopy and vaginoscopy prior to reconstructive surgery in patients with an anorectal malformation.

PURPOSE: First, to assess the number of patients with anorectal malformations (ARM) in whom additional urological and/or gynecological anomalies were identified through routine screening with cysto- or vaginoscopy prior to reconstructive surgery. Second, to assess potential procedure-related complications. METHODS: Retrospective mono-center cohort study, including all ARM patients born between January 2019 and December 2022. Routine screening consisted of cystoscopy for male patients, with the addition of vaginoscopy for female patients. Chi-square was used to compare the screening percentages over time. RESULTS: In total, 38 patients were included, of whom 27 (71.1%) underwent cystoscopy ± vaginoscopy, without the occurrence of complications. Nine of 13 females (69.2%) underwent cysto- and vaginoscopy and 18 of 25 males (72.0%) underwent a cystoscopy. The percentage of patients that underwent these procedures improved over the 2 time periods (50.0% in 2019-2020 vs 90.0% in 2021-2022, p = 0.011). In 15 of 27 patients (55.6%) that underwent cystoscopy ± vaginoscopy, additional anomalies were found that were not identified through physical examination or US-kidney. CONCLUSIONS: In 56% of the patients that underwent cysto- ± vaginoscopy, additional anomalies were identified that were not with imaging studies or physical examination. This study emphasizes the potential benefit of routine cysto- and vaginoscopy in the diagnostic work-up of children with ARM. LEVEL OF EVIDENCE: III.

Appendicitis and its associated mortality and morbidity in infants up to 3 months of age: A systematic review.

Background and Aims: Although appendicitis is rare in young infants, the reported mortality is high. Primary aim of this systematic review was to provide updated insights in the mortality and morbidity (postoperative complications, Clavien-Dindo grades I-IV) of appendicitis in infants ≤3 months of age. Secondary aims comprised the evaluation of patient characteristics, diagnostic work-up, treatment strategies, comorbidity, and factors associated with poor outcome. Methods: This systematic review was reported according to the PRISMA statement with a search performed in Pubmed, Embase and Web of Science (up to September 5th 2022). Original articles (published in English ≥1980) reporting on infants ≤3 months of age with appendicitis were included. Both patients with abdominal appendicitis and herniated appendicitis (such as Amyand's hernia) were considered. Data were provided descriptively. Results: In total, 131 articles were included encompassing 242 cases after identification of 4294 records. Overall, 184 (76%) of the 242 patients had abdominal and 58 (24%) had herniated appendicitis. Two-hundred (83%) of the patients were newborns (≤28 days) and 42 (17%) were infants between 29 days and ≤3 months of age. Either immediate, or after initial conservative treatment, 236 (98%) patients underwent surgical treatment. Some 168 (69%) patients had perforated appendicitis. Mortality was reported in 20 (8%) patients and morbidity in an additional 18 (8%). All fatal cases had abdominal appendicitis and fatal outcome was relatively more often reported in newborns, term patients, patients with relevant comorbidity, nonperforated appendicitis and those presented from home. Conclusion: Mortality was reported in 20 (8%) infants ≤3 months of age and additional morbidity in 18 (8%). All patients with fatal outcome had abdominal appendicitis. Several patient characteristics were relatively more often reported in infants with poor outcome and adequate monitoring, early recognition and prompt treatment may favour the outcome.

Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture.

BACKGROUND: Transition of care (TOC; from childhood into adulthood) of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) ensures continuation of care for these patients. The aim of this international study was to assess the current status of TOC and adult care (AC) programs for patients with ARM and HD. METHODS: A survey was developed by members of EUPSA, ERN eUROGEN, and ERNICA, including patient representatives (ePAGs), comprising of four domains: general information, general questions about transition to adulthood, and disease-specific questions regarding TOC and AC programs. Recruitment of centres was done by the ERNs and EUPSA, using mailing lists and social media accounts. Only descriptive statistics were reported. RESULTS: In total, 82 centres from 21 different countries entered the survey. Approximately half of them were ERN network members. Seventy-two centres (87.8%) had a self-reported area of expertise for both ARM and HD. Specific TOC programs were installed in 44% of the centres and AC programs in 31% of these centres. When comparing centres, wide variation was observed in the content of the programs. CONCLUSION: Despite the awareness of the importance of TOC and AC programs, these programs were installed in less than 50% of the participating centres. Various transition and AC programs were applied, with considerable heterogeneity in implementation, content and responsible caregivers involved. Sharing best practice examples and taking into account local and National Health Care Programs might lead to a better continuation of care in the future. LEVEL OF EVIDENCE: III.

Biomarker-guided neuromodulation aids memory in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset of patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment.