A novel GRK2 variant in a patient with Jeune asphyxiating thoracic dysplasia accompanied by Morgagni hernia.

Skeletal ciliopathies constitute a subgroup of ciliopathies characterized by various skeletal anomalies arising from mutations in genes impacting cilia, ciliogenesis, intraflagellar transport process, or various signaling pathways. Short-rib thoracic dysplasias, previously known as Jeune asphyxiating thoracic dysplasia (ATD), stand out as the most prevalent and prototypical form of skeletal ciliopathies, often associated with semilethality. Recently, pathogenic variants in GRK2, a subfamily of mammalian G protein-coupled receptor kinases, have been identified as one of the underlying causes of Jeune ATD. In this study, we report a new patient with Jeune ATD, in whom exome sequencing revealed a novel homozygous GRK2 variant, and we review the clinical features and radiographic findings. In addition, our findings introduce Morgagni hernia and an organoaxial-type rotation anomaly of the stomach and midgut malrotation for the first time in the context of this recently characterized GRK2-related skeletal ciliopathy.

Variations in Epithelial Lining of Duplication Cysts Cannot be Explained by Known Theories.

Objectives. Duplication cysts are found in any part of the gastrointestinal tract from the oropharynx to anus. Although duplication cysts usually have similar epithelium with the adjacent organ, respiratory epithelium in the enteric duplication cysts is rarely reported. This study was performed to evaluate the variations in the epithelial lining of duplication cysts and its clinical implications. Methods. Patients diagnosed with duplication cysts between 2012 and 2022 were retrospectively reviewed to assess their histopathological results, clinical aspects, treatment options, and demographic characteristics. Results. Twenty-five patients were included. The mean age was 4 years, male-to-female ratio was 15:10. The localizations of duplication cysts were ileum (n = 12), duodenum(n = 4), stomach(n = 3), jejunum(n = 2), colon(n = 2), thoracoabdominal(n = 2), and rectum(n = 1). Most common presentation was abdominal pain (36%). Intestinal (48%) and gastric (40%) epithelia were the most common finding. Four patients (16%) had respiratory epithelium: two in foregut duplication cysts, one each in ileal, and rectal duplications. Twenty-four percentage of patients had associated anomalies. Surgical interventions were performed on 22 patients. Conclusion. Duplication cysts show a wide range of epithelial linings. Respiratory epithelium can be found in not only foregut duplication cysts but also midgut and hindgut duplication cysts. Although the presence of respiratory epithelium did not have any impact on clinical findings, none of the previous theories explain the presence of respiratory epithelium different from foregut duplications.

The role of malnutrition on outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19.

BACKGROUND: Malnutrition increases the complications and mortality in critically-ill children. We performed a retrospective analysis to define the impact of malnutrition on the outcomes of multisystem inflammatory syndrome in children (MIS-C) due to COVID-19. METHODS: Patients with MIS-C were evaluated for demographic features, anthropometric parameters, clinical findings and outcomes. Patients with z scores of body mass index (> 5 years) and weight-for-age (< 5 years) < -2 were considered malnourished. Sarcopenia was defined by total psoas muscle area (tPMA), calculated on abdominal computed tomography (CT) at the level of L3 and L4 vertebrae. The z scores <- 2 for tPMA were considered sarcopenia. The results of patients with and without malnutrition were compared. RESULTS: Twenty-seven patients were included. Forty-four percent (n=12) of patients had malnutrition. Malnutrition was classified as mild to moderate (1/3), severe (1/3) and overweight (1/3). Eighty-two % of cases had acute malnutrition. Among MIS-C symptom criteria, rash was significantly higher in children with malnutrition (p<0.05). Laboratory investigations showed higher ferritin levels in patients with malnutrition (p<0.05). The median tPMA and sarcopenia were significantly higher in patients with malnutrition when compared to patients without malnutrition (42% vs 7%, p<0.05). The oral feeding time, complication rates, and length of hospital stay were similar in both groups (p>0.05). CONCLUSION: Children with MIS-C already had mild to severe malnutrition at admission. Rash and higher ferritin levels were more common in patients with malnutrition. In addition to anthropometric parameters, sarcopenia calculated using tPMA can be used to predict malnutrition in critically-ill children.

European Pediatric Surgeons' Association Survey on Timing of Inguinal Hernia Repair in Premature Infants.

AIM: This article evaluates the practice patterns of European Pediatric Surgeons' Association (EUPSA) members regarding the timing of inguinal hernia (IH) repair in premature infants. METHODS: Online survey containing 29 questions distributed to EUPSA members during January 2023. RESULTS: A total of 180 responds were received. Overall, IH repair prior to discharge was favored by 60% of respondents when there was a history of incarceration and 56% when there was not. In the case of very/extremely premature infants (< 32 weeks) with no history of incarceration, fewer (43%) respondents postpone the surgery until after discharge. The majority of respondents cited the risk of incarceration as the reason for advocating surgery prior to discharge, whereas a reduced risk of apnea was the most cited reason for respondents who prefer delayed surgery. Open approach under general anesthesia was favored by 54% of respondents, with 27% of them preferring open approach with spinal anesthesia. Laparoscopic surgery for premature infants is used in 11% while 7% of them preferred in all premature infants including extremely/very premature ones. Contralateral side evaluation was never done by 40% of respondents and 29% only performed it only during laparoscopic repair. The majority of respondents (77%) indicated that they have an overnight stay policy for premature infants < 45 weeks of gestation. CONCLUSION: There is variation in the practice patterns of pediatric surgeons in the treatment of IH in premature infants. Due to the concern for the high risk of incarceration, IH repair before discharge was the most prevalent practice. Lower risk of postoperative apnea was cited as the most common reason for delaying surgery. Randomized studies are required to establish the optimal timing for IH repair in premature infants.

Magnet ingestion in growing children: a multi-center observational study on single and multiple magnet incidents.

Over the past 15 years, there has been a noticeable uptick in incidents involving children ingesting multiple magnetic foreign bodies which can cause injuries and gastrointestinal complications including death. The current study aimed to identify the prevalence, clinical presentation, and management of single or multiple magnet ingestions. A retrospective multi-central cross-sectional study was conducted to include all pediatric patients < 18 years presented to the emergency department with ingestion of single or multiple magnets and admitted across hospitals in Qatar, UAE, KSA, Tunisia, and Turkey between January 2011 and December 2021. Demographics, symptoms, management, and outcomes were analyzed. There were 189 magnet ingestions, of which 88 (46.6%) were multiple magnet ingestions. Most patients (55.6%) were male, and the median age was 3.9 (IQR 2-7) years. An abdominal X-ray was obtained in all cases. 119 (62%) patients were conservatively treated, 53 (28%) required surgical intervention and 17 (8.9%) underwent gastroscopy. None of the patients with single magnet ingestions experienced morbidity or severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations, perforations (44.3%), severe intestinal necrosis (19.3%), peritonitis (13.6%), severe abdominal infection (10.2%), and septic shock (4.5%). The rate of surgical intervention (59.1% vs. 1.0%) and gastroscopy (15.9% vs. 3.0%) was significantly higher in the multiple ingestion group compared to the single magnet ingestion group. No deaths were identified. A high risk of serious complications, including the need for surgery to remove the magnets and substantial morbidity may result from swallowing more than one magnet. Magnet safety requirements, public education, and improved legislation are urgently required.

AP-1-dependent fibrosis: Exploring its potential role in the pathogenesis of placental transmogrification of the lung (PTL) via tissue-level transcriptome analysis.

Placental transmogrification of the lung (PTL) is a rare pulmonary condition characterized by the presence of immature placental villous structures. The etiology and molecular mechanisms underlying this disease remain largely unknown. This functional study aimed to identify the molecular signatures in the pathogenesis of PTL via comprehensive transcriptome analysis. Comparative transcriptomic assessment of PTL tissue and stromal cells showed differential expression of 257 genes in PTL tissue and 189 genes in stromal cells. Notably, several transcription factors and regulators, including FOSB, FOS, JUN, and ATF3, were upregulated in PTL tissue. Additionally, genes associated with the extracellular matrix and connective tissue, such as COL1A1, MMP2, and SPARC, were significantly altered, indicating possible fibrotic changes. Gene set enrichment analysis highlighted the role of vascular development and extracellular matrix organization, and the Activator Protein-1 (AP-1) transcription factor was significantly activated in PTL tissue. Furthermore, the analysis highlighted an overlap of 25 genes between PTL tissue and stromal cells, underscoring the importance of shared molecular pathways in the pathogenesis of PTL. Among the shared genes, JUND, COL4A2, COL6A2, IGFBP5, and IGFBP7 were consistently upregulated, highlighting the possible involvement of AP-1-mediated signaling and fibrotic changes in the pathogenesis of PTL. The present findings pave the way for further research into the molecular mechanisms underlying PTL and offer novel insights for therapeutic interventions. Given the rarity of PTL, these molecular findings represent a significant step forward in our understanding this enigmatic disease.

Determining the Risk Factors for Anastomotic Stricture Development after Esophageal Atresia Repair: Results from the Turkish Esophageal Atresia Registry.

INTRODUCTION: Anastomotic stricture (AS) is the second most common complication after esophageal atresia (EA) repair. We aimed to evaluate the data in the Turkish Esophageal Atresia Registry to determine the risk factors for AS development after EA repair in a large national cohort of patients. METHODS: The data between 2015 and 2021 were evaluated. Patients were enrolled into two groups according to the occurrence of AS. Patients with AS (AS group) and without AS (non-AS group) were compared according to demographic and operative features, postoperative intubation status, and postoperative complications, such as anastomotic leaks, fistula recanalization, and the presence of gastroesophageal reflux (GER). A multivariable logistic regression analysis was performed to define the risk factors for the development of AS after EA repair. RESULTS: Among the 713 cases, 144 patients (20.19%) were enrolled into the AS group and 569 (79.81%) in the non-AS group. The multivariable logistic regression showed that, being a term baby (odds ratio [OR]: 1.706; p = 0.006), having a birth weight over 2,500 g (OR: 1.72; p = 0.006), presence of GER (OR: 5.267; p < 0.001), or having a recurrent tracheoesophageal fistula (TEF, OR: 4.363; p = 0.006) were the risk factors for the development of AS. CONCLUSIONS: The results of our national registry demonstrate that 20% of EA patients developed AS within their first year of life. In patients with early primary anastomosis, birth weight greater than 2,500 g and presence of GER were risk factors for developing AS. When patients with delayed anastomosis were included, in addition to the previous risk factors, being a term baby, and having recurrent TEF also became risk factors. LEVEL OF EVIDENCE: III.