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.

Dynamic Imaging Grade of Swallowing Toxicity in Children with Esophageal Atresia.

INTRODUCTION: The Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale was developed to evaluate the safety, efficiency, and overall pharyngeal swallowing performance in patients with dysphagia (DIGESTs, DIGESTe, and DIGESTt, respectively). Although various types of swallowing dysfunction are encountered in children with esophageal atresia (EA), oropharyngeal dysphagia poses risk for aspiration. Therefore, a retrospective study was performed to evaluate the safety and efficacy of swallowing by using DIGEST score in children with EA. PATIENTS AND METHODS: Thirty-nine EA patients were included. The demographic features, respiratory problems, results, and outcomes of surgical treatment were evaluated from medical records. The videofluoroscopic swallowing evaluation investigated for both airway protection and bolus residuals at the level of vallecula, posterior pharyngeal wall, and pyriform sinus at liquid and pudding consistencies. The penetration and aspiration scale (PAS) was used to define penetration and aspiration severity, and DIGEST was used to evaluate DIGESTs, DIGESTe, and DIGESTt. RESULTS: The median age of the patients were 13 months (7-39 months), and male-to-female ratio was 25:14. Sixty-seven percent of patients were type-C EA and 61% of them has associated anomalies; 38% of patients had aspiration (PAS = 6-8) in liquids and 10% in pudding consistency. Life-threatening/profound swallowing dysfunction in DIGESTe (DIGEST = 4) was seen in 13% (n = 5) of patients; 40% of EA patients showed severe problems in DIGESTt. CONCLUSION: DIGEST is a valid and reliable tool to define the efficacy and safety of swallowing in children with EA.

The cause of dysphagia in patients with esophageal atresia: a systematic review and meta-analysis.

PURPOSE: Dysphagia is the most common symptom in patients with esophageal atresia (EA) of all ages. There is no study addressing the direct relation between dysphagia and surgical results. Therefore, a systematic review was performed to define the relationship between surgical complications and dysphagia in patients with EA. METHODS: The systematic review was drafted under PRISMA guidelines. Systematic literature search was performed for the period 2000 (Jan) to 2019 (Dec)-20 years-in the databases: MEDLINE, EMBASE, and PubMed. Statistical analysis was performed using Comprehensive Meta-Analysis Version 3.0 software. RESULTS: Among 767 articles, 486 abstracts were screened for the inclusion criteria. The full-texts of 64 articles were assessed for eligibility. The sub-group analysis could be performed in 4 articles for anastomotic strictures. Heterogeneity was calculated by I2 statistic as 18,487 and pooled odds ratio was measured under the fixed effect model (Q = 3.68; P = 0.298, I2 = 18,487). There was no significant relationship with an odds ratio of 1.37 between anastomotic stricture (AS) and dysphagia (95% CI 0.631-2.973, p = 0.426). There was no publication bias for the data (Begg's test, p = 0.496; Egger's tests, p = 0.335). CONCLUSION: This meta-analysis did not reveal a significant relationship between AS and dysphagia in children with EA. Since many other factors contribute to dysphagia, comprehensive variable information such as detailed standardized registry systems for rare diseases for pooling analysis is needed regarding other potential factors including surgical complications.

Continuous Hepatogonodal and Splenogonogal Fusion: A Rare Cause of Bilateral Intra-Abdominal Testis in an 18-Month-Old Boy.

The fusion of gonadal structures with internal organs is very rare. The close proximity between the left gonad and spleen during embryogenesis may result in splenogonadal fusion (SGF). Moreover, the trapping of hepatocyte-destined mesenchyme cells in gonads is defined as hepatogonadal fusion (HGF). The fusion of gonads with intra-abdominal organs may be continuous and may impair testicular descent during the prenatal period. We herein report an 18-month-old boy presented with bilateral nonpalpable testis due to concomitant continuous HGF and SGF. To our knowledge, this is the first case of concomitant HGF and SGF in a boy with bilateral intra-abdominal testis. Laparoscopic excision of fibrous cords and orchidopexy can be achieved despite continuous fusions.

Management of acute abdomen during the active disease course of COVID-19 and multisystem inflammatory syndrome in children.

PURPOSE: To evaluate the management of children with severe gastrointestinal symptoms during the disease course of COVID-19 and multisystem inflammatory syndrome (MIS-C). METHODS: After ethical approval, we reviewed the medical records, retrospectively, of children with COVID-19 or MIS-C requiring surgical consultation for severe gastrointestinal symptoms. RESULTS: The subjects comprised 15 children, 13 with MIS-C and 2 with COVID-19. Twelve children (80%) had been in known close contact with a person with SARS-CoV-19 and 13 were positive for Anti-SARS-CoV-2 IgG. All the children had experienced fever for at least 1 day and had signs of involvement of two or more systems. Three patients required surgical intervention: one underwent surgical exploration with a presumptive diagnosis of acute appendicitis in the referring center and was transported to our center following clinical deterioration, where a diagnosis of MIS-C was confirmed; and the remaining two developed appendicitis during hospitalization for COVID-19. All three patients had a longer duration of abdominal pain, a higher number of lymphocytes, and a lower level of inflammatory markers than the non-surgically managed patients. None of the patients presenting with MIS-C underwent surgical exploration. CONCLUSION: Gastrointestinal involvement may mimic acute abdomen in children with COVID-19. Thus, children presenting with acute abdomen in the pandemic era require careful evaluation and prompt diagnosis to avoid unnecessary surgical intervention.

Environmental exposure in the etiology of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.

PURPOSE: To investigate the occupational and environmental factors in the etiology of infantile hypertrophic pyloric stenosis (IHPS). METHODS: Protocol was drafted according to the PRISMA guidelines and registered on PROSPERO (CRD42020152460). A search for a combination of terms related to IHPS, fetus and neonates, and environmental exposure was performed for studies published between 2000 and 2020 in the EMBASE, Pubmed, and MEDLINE databases. RESULTS: Overall, 2203 abstracts were identified and 829 were screened. The full text of the selected articles (N = 98) was assessed for eligibility. Fifteen studies were included in quantitative synthesis. IHPS risk was significantly lower in black and Hispanic mothers than in white mothers [OR 0.47 (95% CI 0.44-0.51, p < 0.001), OR 0.85 (95% CI 0.77-0.94, p = 0.002), respectively]. Lower maternal education level and maternal smoking were risk factor for IHPS. We further observed a non-significant association between maternal folic acid usage and IHPS risk. Data were insufficient to evaluate occupational exposure. CONCLUSION: This review provides an understanding of the role of environmental exposures in IHPS etiology. Lower maternal educational level, maternal smoking, and white ethnicity are associated with a significantly increased risk of IHPS, while folic acid use seems non-significantly associated with IHPS risk. LEVEL OF EVIDENCE: III.

Feasibility, Reliability, and Validity of the Turkish Version of the Esophageal-Atresia-Quality-of-Life Questionnaires to Assess Condition-Specific Quality of Life in Children and Adolescents Born with Esophageal Atresia.

BACKGROUND: This study reports the feasibility, validity and reliability of the Turkish versions of the Esophageal-Atresia-Quality-of-Life (EA-QOL) questionnaires, which were originally developed in Sweden and Germany. METHODS: After translation from Swedish to Turkish and cognitive debriefings, 51 families of children aged 2 to 7 years (parent-report, 17-items) and 54 families of children 8 to 17 years (child and parent-report, 24-items) responded to the EA-QOL questionnaires and a validated generic HRQOL-instrument (PedsQL4.0). Medical records of patients and questionnaires were used to obtain clinical data. The Turkish version of the EA-QOL questionnaires were evaluated for feasibility (<5% missing item responses), reliability (internal consistency/retest reliability for 3 weeks) and validity (known-groups/concurrent/convergent). Level of significance was p<0.05. RESULTS: Feasibility of the Turkish version of the EA-QOL questionnaires was good. Internal consistency of all scales was satisfactory, as were the level of agreements of EA-QOL scores between the field- and retest study. Known-group and concurrent validity were achieved since the EA-QOL questionnaires showed that esophageal symptoms and feeding difficulties were negatively associated with EA-QOL total scores in both age specific versions (child-and parent report), and respiratory symptoms in the version for EA children 2 to 7 years (parent-report). A higher number of respiratory symptoms decreased the EA-QOL total scores in both age groups (parent-report, p<0.05). Correlations between the EA-QOL total scores and PedsQL-4.0 total scores supported convergent validity. CONCLUSION: The Turkish version of the EA-QOL questionnaires are feasible, valid and reliable to assess condition-specific HRQOL in EA children.

A rare congenital esophageal anomaly mimicking an isolated esophageal atresia: Kluth Type IV1a membranous esophageal atresia.

Congenital esophageal web is a very rare type of esophageal atresia (EA) and is considered as Type IV atresia in Kluth's classification. Type IV EA is further classified into subgroups according to the location of web and the presence of tracheoesophageal fistula (TEF). Herein, we present a newborn having Type IV1a EA who was initially suspected as isolated EA and has co-existing malrotation together with the review of the literature. A newborn having congenital esophageal web was admitted with antenatal ultrasonography revealing polyhydramnios, dilated stomach, and duodenum. Abdominal X-ray revealed a gasless abdomen suggesting isolated EA. The upper gastrointestinal series confirmed complete obstruction at the lower esophagus. Bronchoscopy performed excluding TEF. Laparotomy revealed intestinal malrotation and the absence of another GI webs. Gastrotomy was performed and mucosal web at GEJ was seen by pushing nasogastric catheter. Web excision and Ladd procedure were performed. Congenital esophageal web is an extremely rare type of esophageal anomaly that can be only classified in Kluth classification. A high index of suspicion is required for diagnosis especially in newborns with the gasless abdomen and esophageal obstruction at the level of GEJ. Preoperative bronchoscopy is mandatory to exclude an associating TEF. Surgical exploration via laparotomy is beneficial for exploring additional GIS anomalies.

Protocol: A systematic review and meta-analysis of the role of fetal and infantile environmental exposure in etiopathogenesis of infantile hypertrophic pyloric stenosis.

Infantile hypertrophic pyloric stenosis (IHPS) is one of the hallmark pediatric surgical diseases. However, its etiology remains incompletely understood. By systematically reviewing the literature, we aim to clarify the effect of the effect of occupational and environmental factors and role of nitric oxide (NO) metabolism in the etiopathogenesis of IHPS. The systematic review is drafted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). Systematic literature search will be performed for the period 2000 (Jan) to 2020 (Dec) in the databases: MEDLINE, EMBASE, PubMed. The systematic search will cover the literature in English and Turkish language and will be limited to studies on human subjects. Four investigators will independently search the databases (MEDLINE, EMBASE, PubMed) according to the defined search strategy. The full-text of the selected articles will be screened independently by four reviewers, against the inclusion criteria. Descriptive data will be extracted from each study regarding: study details, methods, participants, outcomes and calculations of association for potential further statistical analysis. If meta-analysis could not be undertaken, systematic approach to analyzing the findings of included multiple studies will be described. Heterogeneity will be assessed by quantifying the inconsistency across studies using I2 statistic. Statistical analysis will be performed using Comprehensive Meta-Analysis Version 3.0 software. The p values lower than 0.05 will be considered statistically significant for all analyses.

Challenges in management and prognosis of pediatric intestinal pseudo-obstruction.

BACKGROUND/AIMS: Pediatric intestinal pseudo-obstruction (PIPO) is the most severe form of intestinal dysmotility in children. This study aims to present the cases of PIPO to discuss its diagnosis, management, and prognosis. MATERIALS AND METHODS: We retrospectively analyzed the medical records of the patients with PIPO between 2010 and 2018. RESULTS: A total of 7 patients were included. The admission age was 3 days-10 years. The complaints were abdominal distention and constipation in all the patients. All the patients had passed meconium in the first 48 hours of their life. An upper gastrointestinal (GI) series revealed slow transit in 6 patients and malrotation in 2 patients. Full-thickness rectum biopsies revealed normal ganglion cells. Neurological examination revealed postinfectious pandysautonomy in 1 patient. Furthermore, 2 patients are under follow-up with ileostomy and TPN, 1 patient is with enteral feeding and ileostomy, and 3 patients are stable with pyridostigmine, enemas. Moreover, 1 patient died because of sepsis. The prognosis was not significantly correlated with initial presentation time, lag time, and presence of extraintestinal manifestations (p>0.05). The prognosis was significantly better when fewer number of operations were performed (p=0.029) Conclusion: PIPO is a broad-spectrum disease group that is difficult to diagnose and treat. It is mandatory to rule out the secondary causes of diagnosis. Medical and surgical treatments are used to support the nutritional status, prevent sepsis, and restore the intestinal motility. The prognosis was better when the secondary causes were identified and fewer operations were performed.

The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats.

BACKGROUND: In this study, we aimed to examine the therapeutic effects of ozone on the acute phase of intestinal ischemia-reperfusion (I/R) injury in rats to resemble clinical practice. METHODS: Eighteen Wistar albino rats were assigned to control (CG, n=6), sham (SG, n=6) and ozone groups (OG, n=6). A midline laparotomy was performed and a superior mesenteric artery (SMA) in the SG and OG was occluded with a 0/0 catgut suture, but in the CG, the incision was closed without any intervention. Tissue oxygenation was monitored with a tissue oxygenation monitor to achieve the same grade during intestinal ischemia. The incision was closed and, in the OG, ozone/oxygen mixture (0.7 mg/kg) was injected intraperitoneally, 20 minutes before reperfusion. Surgical incision was reopened and reperfusion was achieved after 60 minutes of ischemia in the SG and OG. After 60 minutes of reperfusion, 2 cm small intestine segment was sampled for histopathological assessment of the intestinal mucosal damage (Chiu score) and biochemical assessment of oxidative stress markers (nitric oxide: NO, malondialdehyde: MDA, superoxide dismutase: SOD) in all groups. RESULTS: The Chiu scores of the SG and OG were statistically increased than that of the CG (p=0.002; and p=0.002, respectively). Chiu score in the OG was higher compared to that in the SG, but not statistically significant (p=0.175). MDA levels were statistically higher in the SG and OG than that of the CG (p=0.004; and p=0.010, respectively). However, the difference between the SG and OG was not statistically significant (p=0.522). SOD and NO levels were not significantly different between groups (p=0.451 and p=0.056, respectively). CONCLUSION: Contrary to the literature, single-dose ozone therapy did not reduce the oxidative stress or improve the ischemic damage in intestinal I/R injury in rats. Further evaluation with different doses in different time periods is needed for potential clinical use.

Cystoscopy-Guided Laparoscopic Excision of Prostatic Utricle: Report of a Case.

Prostatic utricle (PU) is incomplete regression of Müllerian duct and may cause recurrent urinary tract infections (UTIs), stone formation, postvoid dribbling, and recurrent epididymitis. Although surgical excision is recommended to avoid complications, surgical access to PU has been challenging. Cystoscopy-guided laparoscopic management of PU in a 3-year-old boy is reported to discuss use of other endoscopic aids in the surgical treatment of PU. He was admitted with disordered sexual development with karyotype of 47,XYY/46,XY and has been experiencing recurrent UTIs. Voiding cystourethrogram (VCU) demonstrated large PU (IKOMA II). Cystoscopy was performed confirming PU and the cystoscope was left in situ to aid laparoscopic exploration after bladder was emptied. A 5-mm umbilical port and two 5-mm ports in both lower quadrants were inserted. The peritoneum was dissected behind bladder. The cystoscope in PU was used as guidance in identification and dissection of PU. The vas deferens was identified and could be secured. The neck of PU was ligated with surgiloop. PU was retrieved from umbilical port. Postoperative VCU revealed normal posterior urethra. He has been free of UTIs for the last 6 months. Laparoscopy is safe and feasible alternative in surgical management of PU, by providing good visual exposure, easy dissection in deep pelvis, and improved cosmesis. The cystoscopic guidance is an important aid in identification and dissection of PU.

New scoring system to predict foreign body aspiration in children.

PURPOSE: To propose a new scoring system to predict foreign body aspiration (FBA) in children. METHODS: Children who underwent bronchoscopy for FBA were evaluated for age, sex, history of aspiration, physical examination, radiological findings and results of bronchoscopy retrospectively. A new proposed FBA scoring including statements about history, physical and radiological findings were applied to all patients to define a total score. The results of each statement and total FBA score were compared according to bronchoscopy findings. The sensitivity and specificity of FBA score and cut-off values of total FBA score to predict positive cases were evaluated. RESULTS: Totally 720 patients with a male to female ratio of 227:133 were included. FBA was noted in 52.1% (n=375) of cases. When the scoring system compared with the existence of foreign body (FB), the patient history had no statistical significance to predict positive cases (p>0.05). The existence of FB was significantly associated with physical examination, radiological findings and total FBA score (p<0.001). The revised scoring system without history parameters had range of total scores 0 to 5. The total scores were obtained by sum of physical findings and radiological parameters and the cut-off value of 2 had the highest diagnostic performance with sensitivity and specificity of 77.9% and 74.8% to predict FBA in children. CONCLUSION: Our results suggest that the proposed scoring system can be utilized to predict FBA in children. The total score higher than 2 is predictive for FBA. Although, physical and radiologic findings are strong parameters for positive bronchoscopy, the history of FBA has no diagnostic utility. LEVEL OF EVIDENCE: Level III (retrospective comparative study) STUDY TYPE: Diagnostic study.

Acquired Tracheoesophageal Fistula After Esophageal Atresia Repair

Background: Recurrence of tracheoesophageal fistula is a frequent complication after esophageal atresia repair. Acquired tracheoesophageal fistulas are long new fistulas that are localized at sites that are not typical of the congenital tracheoesophageal fistula. We present four cases to discuss the diagnostic and management challenges concerning various acquired tracheoesophageal fistula localizations. Case Report: We retrospectively evaluated the medical records of patients admitted with acquired tracheoesophageal fistula in the last 5 years. Among the 16 postoperative tracheoesophageal fistulas, 4 were classified as acquired tracheoesophageal fistula. Patients' admission age ranged from 1 to 8 years. The female to male ratio was 2:2. The presented cases were admitted with recurrent respiratory tract infections, choking, and coughing. The acquired tracheoesophageal fistulas were observed between the esophagus and cervical trachea, between the esophagus and the right bronchus passing through intrathoracic abscess cavity, in the right bronchus, and between the colon conduit and trachea. One of the acquired tracheoesophageal fistulas healed spontaneously, whereas others required surgical ligation. Conclusion: Acquired tracheoesophageal fistula most often occurs secondary to local or diffuse mediastinitis. Acquired tracheoesophageal fistula may appear at unusual sites not typical of congenital tracheoesophageal fistula, such as esophagus-to-right bronchus and conduit to trachea. Therefore, the unusual locations of acquired tracheoesophageal fistula should be borne in mind, and patients evaluated and managed more comprehensively.

Meconium periorchitis: An incidentally diagnosed rare entity during inguinal herniorraphy.

Durmus G, Boybeyi-Türer Ö, Gharibzadeh-Hizal M, Ekinci S, Kiper N. Meconium periorchitis: An incidentally diagnosed rare entity during inguinal herniorraphy. Turk J Pediatr 2018; 60: 612-614. Meconium periorchitis (MPO) is a rare disorder caused by meconium peritonitis with the leakage of meconium into the scrotal sac through the patent processus vaginalis. MPO may be rarely detected during inguinal hernia repair. The association of MPO with cystic fibrosis is rarely seen. We present a male infant with the complaint of left groin swelling, compatible with reducible inguinal hernia. An herniotomy was carried out and the greenish nodules with calcifications were detected. Histopathological examination was compatible with MPO. Two months later the patient was diagnosed with atypical cystic fibrosis. Clinicians should be aware of MPO presentations and its appearance on the hernia sac to prevent unnecessary orchiectomy.

Does penile tourniquet application alter bacterial adhesion to rat urethral cells: an in vitro study.

PURPOSE: To investigate the effects of penile tourniquet (PT) application on bacterial adhesion to urothelium. METHODS: Fifty-six rats were allocated into control group (CG), sham group (SG), PT group (PTG). No intervention was applied in CG. A 5mm-length urethral repair was performed in SG and PTG. In PTG, a 10-min duration of PT was applied during the procedure and the tissue oxygenation monitor was used to adjust the same degree of ischemia in all subjects. Samples were examined for wound healing parameters and tissue levels of inflammatory markers, eNOS, e-selectin, and ICAM-1antibodies. The adhesion of Escherichia coli to urothelium was investigated with in vitro adhesion assay. RESULTS: Inflammation was higher and wound healing was worse in SG than CG and in PTG in comparison to CG and SG (p<0.05). The endothelial damage, as shown by eNOS expression, was significantly higher in PTG compared to CG and SG (p<0.05). The staining with ICAM-1 and e-selectin antibodies, showing increased inflammatory response to bacterial adhesion, was significantly higher in PTG compared to CG and SG (p<0.05). In vitro urethral cell proliferation was achieved only in CG and SG revealing significantly increased adhesion in SG compared to CG (p<0.05). The PT application caused endothelial corruption and prevented cell proliferation in cell culture. CONCLUSION: The PT application does not improve wound healing and increases bacterial adhesion molecules in penile tissue. The in vitro assays showed that PT causes severe endothelial damage and inhibits endothelial cell proliferation.

Assessment of developmental and radiological long-term outcomeof children with surgically treated midgut volvulus.

BACKGROUND/AIM: The aim is to evaluate the long-term outcome of asymptomatic patients who underwent surgical correction for midgut volvulus. MATERIALS AND METHODS: Seven patients managed surgically for midgut volvulus in the last 3 years were included. Demographic features, symptoms at presentation, diagnoses, surgical procedures, and complications were recorded. Patients were then contacted for follow-up and evaluation of long-term outcomes. General physical conditions, anthropometric parameters, feeding habits, and defecation histories were evaluated. Laboratory examinations were performed. Color Doppler ultrasonography (CDUS) was performed to evaluate blood flow in the superior mesenteric artery (SMA). RESULTS: In total, seven patients were identified. The median age at admission was 3 days (0-90 days). Mean age at follow-up was 17 ± 2 months. Growth parameters were normal in all cases. Four patients had low levels of ferritin and transferrin saturation. One patient had microcytic anemia. Another patient had low serum zinc level. One patient who had ileal resection had a high level of steatorrhea in stool examination. In CDUS, SMA blood flow volume was low in all cases. Peak-systolic velocity and resistance index were low in all but one case. CONCLUSION: Despite uneventful postoperative courses, all patients operated on for midgut volvulus showed mild laboratory changes and decreased blood flow in the SMA in long-term follow-up.