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.

Effect of prostaglandin-E1 treatment on pyloric wall thickness in newborns with ductal-dependent critical congenital heart diseases.

BACKGROUND: Prostaglandin E1 (PGE1) is used in the medical treatment of ductal-dependent critical congenital heart disease (CCHD) in neonates. Apnea/bradycardia, hypotension, hypokalemia, and fever are the most important side effects of PGE1. Moreover, gastric outlet obstruction has been reported in a few case reports. A prospective study was conducted to investigate the effect of PGE1 treatment on pyloric wall thickness in newborns with congenital heart diseases. METHODS: A total of 22 newborns with ductal-dependent CCHD having PGE1 infusion longer than a week were included in this study. Ultrasonographic measurements were performed before and one week after the PGE1 infusion to evaluate the pyloric thickness and length. The protocol was registered with ClinicalTrials.govidentifier NCT04496050. RESULTS: A total of 22 neonates with mean gestational age 38 ± 1.8 weeks and birth weight 3105 ± 611 gr were enrolled in the study. The median time of the second ultrasound was seven days. The median cumulative dose of PGE1 given during this period was 108 mcg/kg/min. There was a statistically significant increase in post-treatment pyloric thickness and length compared to pre-treatment measurements (p < 0.001, p < 0.001). None of the patients with increased thickness and pyloric muscle length presented any symptoms. CONCLUSION: PGE1 treatment significantly increased the pyloric thickness and length after at least one-week treatment. PGE1 with its action mechanism is likely to cause gastric outlet obstruction, although not exactly pyloric stenosis on the condition used for a long time.

Lung ultrasound findings in children with foreign body aspiration.

OBJECTIVES: Foreign body aspiration (FBA) has a wide clinical spectrum, patients may be asymptomatic or present with cardiopulmonary arrest. Radiological imaging methods are used in addition to history and physical examination findings for certain diagnosis. Lung ultrasonography (LUS), whose usage area is increasing year by year, can be included in these. This study aimed to investigate ultrasonography findings in FBA and hypothesized that LUS may have a standard place in FBA diagnosis. METHODS: Patients who administered to the pediatric emergency department between August 2019-August 2021, considered according to the clinical findings and physical examination possible FBA, and who undergone rigid bronchoscopy by pediatric surgery were included in the study. RESULTS: Thirty-two patients were included in the study. According to the results of bronchoscopy, FBA was detected in 25 patients. The most common finding in radiography was hyperinflation on one side, while LUS findings were confluent-B lines in eight patients, barcode-sign in five patients, pleural line abnormalities in two patients, and pleural consolidation in two patients. CONCLUSION: This study is the first study aiming to evaluate LUS findings in FBA to the best of our knowledge. The B-lines, barcode sign, pleural line abnormalities and consolidation are seen findings in LUS of the patients with FBA. Although it is far from replacing chest radiography in these patients, it is possible to say that it has an equivalent value with chest radiography.

The miRNA-24, miRNA-21 expressions and matrix metalloproteinase-7 level in exhaled breath condensate of children with primary spontaneous pneumothorax.

Bullous lung diseases may cause primary spontaneous pneumothorax (PSP) in children. The microRNAs (miRNAs) are non-coding RNAs that participate in regulation of inflammation and cancer. We hypothesized that children with bullous lung disease and PSP may have altered miRNA expressions in their exhaled breath condensates (EBCs). Therefore, a prospective study was performed to evaluate the miRNA-24 and 21 expression, and the matrix metalloproteinase-7 (MMP-7) levels in EBC of children with PSP. Children with PSP were evaluated for age, gender, clinical features and results of surgical treatment. EBC samples (500-1000 ml) were collected to evaluate the miRNA-21, 24 expressions, and MMP-7, and tissue-inhibitor-MMP-1 (TIMP-1) levels. miRNA expressions and MMP levels of patients were compared with healthy controls (control group (CG),n= 12). Subjects (n= 16) with a mean age of 15 years (10-19 years), and a male-to-female ratio of 14:2 were enrolled in this study. The most common presenting symptom was sudden chest pain (n= 14). In 62.5% of the cases an underlying bullous lung disease were detected. During an average of 16.6 months (1-60 months) follow up period, four subjects relapsed. The mean MMP-7 (1.74-1.57 ng ml-1), and TIMP-1 (1.92-1.84 ng ml-1) levels were similar between both groups (p> 0.05). miRNA-24 expression was significantly decreased in the PSP group, when compared to the CG (0.16-1 2-ΔΔCT,p< 0.05). In addition, the miRNA-21 expression was not different between the two groups (p> 0.05). In conclusion, the miRNA-24 levels were significantly decreased in children with PSP. Taken together, children with PSP, especially those with bullous disease, should be closely monitored in the long-term period.

Evaluation of the predictability of clinical and radiological findings in the diagnosis of malrotation.

BACKGROUND: To evaluate the predictability of clinical and radiological findings in the diagnosis of malrotation. METHODS: Between 2010 and 2020, children with presumptive diagnosis of malrotation were included. The demographic features, clinical and radiological findings, operative findings and outcome were recorded. The upper gastrointestinal series (UGIS) were evaluated by two radiologists. All parameters were correlated with surgical findings to evaluate the predictability. RESULTS: Seventy patients were included. The presenting symptom was bilious vomiting in 29 cases (41.4%), and atypical symptoms (non-bilious vomiting, food refusal, etc.) in 40 cases (57%). One of the cases (1.6%) was asymptomatic and diagnosed incidentally during UGIS. 52 cases had abdominal X-ray and 14 (26.9%) of them were normal. Doppler ultrasonography (US) (n=20) revealed evidence of malrotation in 13 cases (65%). The location of duodenojejunal junction (DJJ) in UGIS was compatible with malrotation in 33 cases. 48 (61%) cases underwent surgical exploration; 35 cases had malrotation and seven cases had midgut volvulus. Median followup time was one year (0.5-7 years). Volvulus has recurred in one case and another case operated for volvulus died because of short bowel syndrome. The statistical analysis for predictability revealed that bilious vomiting (sensitivity: 57.1%, specificity: 82.1%), Doppler US (sensitivity: 92.3%, specificity: 75%) and right-sided DJJ in UGIS (sensitivity: 96.8%, specificity: 75%) have highest predictability. CONCLUSIONS: The bilious vomiting, Doppler US findings and right-sided DJJ have the highest predictability to confirm the diagnosis. However, presenting with atypical symptoms and having atypical or normal findings in UGIS do not rule out malrotation.

Extracorporeal shock wave lithotripsy in the management of a 14-year-old girl with chronic calcific pancreatitis.

BACKGROUND: Chronic pancreatitis is very rare in childhood and causes chronic/relapsing abdominal pain, frequent hospitalizations, malnutrition, growth retardation, and stone formation in the main duct. Although pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is commonly used in the treatment of pancreatic stones (PS) in adults, the use in children is still controversial. An adolescent girl with multiple PS is presented to discuss the use of ESWL as a treatment alternative in children with PS. CASE: A 14-year-old girl was admitted with abdominal pain and elevated pancreatic enzyme levels. Abdominal US showed irregularity and rough echogenicity in pancreas revealing pancreatitis. Multiple stones were seen in main pancreatic duct on Magnetic resonance cholangiopancreatography (MRCP). Endoscopic retrograde cholangiopancreatography (ERCP) was performed and dilated pancreatic duct, thickened pancreatic secretion were detected. Endoscopic sphincterotomy was performed. Endoscopic removal of stones could not be achieved since the largest stone was 17x8 mm. Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) was performed using electromagnetic lithotripter under general anesthesia. Following ESWL, fragmentation of stones in the main duct was confirmed with ERCP. After 3 sessions of ESWL, no ESWL-related complication was observed. Pain relief was achieved. The patient is still under follow-up regarding endocrine and exocrine function of pancreas. CONCLUSION: ESWL may be an effective and safe management option in pediatric PS which could not be removed by ERCP. The patients managed with ESWL should be followed-up for a long time regarding the endocrine and exocrine functions of the pancreas. As in management of adult pancreatitis, clinical guidelines are needed regarding the management of pediatric PS.

Pyloroduodenal intussusception due to diffuse juvenile polyposis in a 3 year-old child: case report.

BACKGROUND: Pyloroduodenal intussusception (PDI) due to gastric and pyloric polyps is very rare and has not been reported previously in children. CASE: A 3 year-old boy was admitted with non-bilious vomiting and abdominal distention. Abdominal X-ray showed gastric air-fluid level and ultrasonography showed 5 cm intussusception at right upper quadrant. Upper gastrointestinal study showed gastric outlet obstruction. Multiple polyps at stomach and pylorus were detected in endoscopy. The explorative laparotomy revealed polyps originating from pylorus passing to duodenum and causing PDI. The polyps were excised to reduce the intussusception via duodenotomy. CONCLUSION: PDI and pyloric polyps should be kept in mind in cases with radiological examinations revealing gastric outlet obstruction.

A rare cause of acute abdominal pain in a patient with Primary ciliary dyskinesia with situs inversus totalis.

Primary ciliary dyskinesia (PCD) is a rare, genetic disease characterized by ciliary dysfunction. Patients may present with respiratory distress during neonatal period; chronic sinopulmonary disease, bronchiectasis, recurrent otitis media, sinusitis and infertility in later periods. About 50% of PCD patients have situs inversus totalis and 6-12% have situs ambiguous known as heterotaxy syndromes. Herein, we present a case of PCD and accompanying situs inversus who had acute abdominal pain and was diagnosed with torsion of one of the multiple spleens. Evaluation of acute abdominal pain in these patients has great importance since the internal organs are not at their typical locations.

The relationship between oxidative stress markers in exhaled breath condensate and respiratory problems in patients with repaired esophageal atresia.

AIM: To evaluate the relationship between respiratory problems and oxidative stress markers in exhaled breath condensate (EBC) of patients with esophageal atresia (EA). METHODS: EA cases with respiratory problems were evaluated retrospectively for age, gender, the type of atresia, surgical treatment, outcome and respiratory symptoms. The results of gastroesophageal reflux (GER) treatment including the use of proton pump inhibitor (PPI) and fundoplication were also documented. EBC samples of 500-1000 µl were obtained by Ecoscreen machine in all cases. The levels of Glutathione (Glut), 8-isoprostane (8-iso), cysteinyl-leukotriene (Cys-LT) were measured with ELISA. Results were compared with healthy control subjects (CG, n = 26) and the relationship between oxidative stress markers and respiratory symptoms was evaluated. The results of GER treatment and oxidative stress markers in EBC were also correlated. RESULTS: Twenty-nine patients with a mean age of 8.8 years (3-14 years) were included. The male/female ratio was 16:13. The EA presented with distal fistula in 27 cases. While no fistula was observed in 1 case, both proximal and distal fistulae were present in another single case. Associated anomalies, most of which were cardiovascular anomalies, were observed in 65.5% (n = 19) of cases. The median Glut level was 1.03 mM/ml (0.93-1.15), iso-8 was 38.8 pg/mL (32.03-76.2) and Cys-LT was 0.44 pg/mL (20.17-61.3) in patients with EA. The median levels of oxidative markers in CG were 1.23 mM/mL (1.13-1.36), 66.3 pg/mL (33.5-106.7), and 56.9 pg/mL (27.4-80.1), respectively. Glut levels were significantly lower in EA cases compared to CG (p = 0.01). There was no significant difference between the groups regarding 8-iso and CYS-LT levels (p = 0.9, p = 1.0). Cys-LT levels were significantly lower in patients with PPI treatment [21.7 pg/mL (18.6-48.1)], when compared to patients without PPI treatment [41.1 pg/mL (22.5-83.1)] (p = 0.04) and healthy subjects [56.9 pg/mL (27.4-80.1)] (p = 0.017). The 8-iso levels were significantly decreased in cases with fundoplication compared to the patients without fundoplication (p = 0.02). CONCLUSION: Glut - an antioxidant agent - levels were significantly lower in EBC of EA cases. The decrease in Cys-LT levels in cases with PPI treatment and in 8-iso levels in patients with fundoplication suggests that the oxidative damage in EBC of EA cases may be correlated with GER and its management. TYPE OF STUDY: Case control study LEVEL OF EVIDENCE: Level III.

Bilateral Pulmonary Langerhans's Cell Histiocytosis is Surgical Challenge in Children: A Case Report.

Background Pulmonary Langerhans's cell histiocytosis (PLCH) is a rare cause of interstitial lung disease in children and more than half of the cases are bilateral. Persistent respiratory distress due to spontaneous pneumothorax (SP) in bilateral PLCH may refractory to conservative treatment and posed a great challenge to surgical modalities. A 3-year-old boy with SP due to bilateral PLCH is presented to discuss the surgical options of recurrent and refractory PLCH cases in children. Case Report The patient was admitted to the emergency department with severe respiratory distress and SP. After chest tube insertion, biopsy from neck mass revealed Langerhans's cell histiocytosis. Chemotherapy including vinblastine and prednisone was initiated. Due to persistent respiratory difficulty and air leaks, talc pleurodesis and thoracoscopic bullae excision with pleural decortication were performed. Two months after the admission, due to nosocomial infection and severe respiratory distress, extracorporeal membranous oxygenation (ECMO) support was initiated. The patient was died of ECMO complications on 24th day of ECMO. Conclusion Despite the use of chemotherapy and surgical excision of cystic lesions, bilateral PLCH in children may have lethal outcome. Other treatment options including respiratory support with ECMO and lung transplantation should be considered as last resort of treatment alternative in persistent cases.

Assessment of pediatric cricopharyngeal achalasia with high resolution manometry.

Boybeyi Türer Ö, Demir N, Ciecieraga T, Günaydin RÖ, Soyer T. Assessment of pediatric cricopharyngeal achalasia with high resolution manometry. Turk J Pediatr 2019; 61: 804-809. Cricopharyngeal achalasia (CPA) is an uncommon cause of oropharyngeal dysphagia (OPD) which is the failure of upper esophageal sphincter (UES) to relax during bolus passage. The diagnostic challenges in OPD have been overcome with the use of high resolution manometry (HRM) in children where a catheter based biomechanical evaluation testing of the oropharyngeal swallowing is performed. Herein, we present a case with severe dysphagia diagnosed as CPA utilizing HRM testing. An 8-year-old boy was seen in our clinic with a two-year history of difficult swallowing, recurrent respiratory tract infections, hypoxia and seizure secondary to aspiration. Esophagography revealed an indentation of the cricopharangeal muscle (CPM) in the cervical part of the esophagus. Videofluroscopic swallow studies (VFSS) revealed cricopharyngeal bar at level of C5-6 and diffuse dysmotility in esophagus. Conventional esophageal manometry revealed absence of peristaltic activity throughout the esophagus. Esophagogastroduodenoscopy revealed narrowing in upper esophagus that with applied force allowed passage of the endoscope. The patient underwent UES dilatation 6 times. He had temporary relief of symptoms. Since he did not have sustained response to dilatation, a botulinium toxin (5IU/each quadrant) injection (BTI) to CPM was performed twice. His symptoms recurred at the end of 3 months. HRM was performed revealing weakness of CPM and uncoordinated contractions and relaxations in UES. We could not reliably differentiate if HRM findings were a sign of primary illness or secondary to BTI. Swallowing rehabilitation was adjusted based on HRM findings. He is still under follow-up with mild dysphagia to certain solids. CPA is an uncommon cause of dysphagia with limited therapeutic options. HRM should be performed in OPD before considering any treatment modality including esophageal dilatation and BTI. HRM has become gold standard diagnostic tool in OPD that provides objective evaluation of pharyngeal and UES motility in children.