Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia.

Orofaciodigital syndrome (OFD) is a genetically heterogeneous ciliopathy characterized by anomalies of the oral cavity, face, and digits. We describe individuals with OFD from three unrelated families having bi-allelic loss-of-function variants in SCNM1 as the cause of their condition. SCNM1 encodes a protein recently shown to be a component of the human minor spliceosome. However, so far the effect of loss of SCNM1 function on human cells had not been assessed. Using a comparative transcriptome analysis between fibroblasts derived from an OFD-affected individual harboring SCNM1 mutations and control fibroblasts, we identified a set of genes with defective minor intron (U12) processing in the fibroblasts of the affected subject. These results were reproduced in SCNM1 knockout hTERT RPE-1 (RPE-1) cells engineered by CRISPR-Cas9-mediated editing and in SCNM1 siRNA-treated RPE-1 cultures. Notably, expression of TMEM107 and FAM92A encoding primary cilia and basal body proteins, respectively, and that of DERL2, ZC3H8, and C17orf75, were severely reduced in SCNM1-deficient cells. Primary fibroblasts containing SCNM1 mutations, as well as SCNM1 knockout and SCNM1 knockdown RPE-1 cells, were also found with abnormally elongated cilia. Conversely, cilia length and expression of SCNM1-regulated genes were restored in SCNM1-deficient fibroblasts following reintroduction of SCNM1 via retroviral delivery. Additionally, functional analysis in SCNM1-retrotransduced fibroblasts showed that SCNM1 is a positive mediator of Hedgehog (Hh) signaling. Our findings demonstrate that defective U12 intron splicing can lead to a typical ciliopathy such as OFD and reveal that primary cilia length and Hh signaling are regulated by the minor spliceosome through SCNM1 activity.

Analysis of alcohol-metabolizing enzymes genetic variants and RAR/RXR expression in patients diagnosed with fetal alcohol syndrome: a case-control study.

Understanding the mechanisms underlying alcohol metabolism and its regulation, including the effect of polymorphisms in alcohol-metabolizing enzymes, is crucial for research on Fetal Alcohol Spectrum Disorders. The aim of this study was to identify specific single nucleotide polymorphisms in key alcohol-metabolizing enzymes in a cohort of 71 children, including children with fetal alcohol syndrome, children prenatally exposed to ethanol but without fetal alcohol spectrum disorder, and controls. We hypothesized that certain genetic variants related to alcohol metabolism may be fixed in these populations, giving them a particular alcohol metabolism profile. In addition, the difference in certain isoforms of these enzymes determines their affinity for alcohol, which also affects the metabolism of retinoic acid, which is key to the proper development of the central nervous system. Our results showed that children prenatally exposed to ethanol without fetal alcohol spectrum disorder traits had a higher frequency of the ADH1B*3 and ADH1C*1 alleles, which are associated with increased alcohol metabolism and therefore a protective factor against circulating alcohol in the fetus after maternal drinking, compared to FAS children who had an allele with a lower affinity for alcohol. This study also revealed the presence of an ADH4 variant in the FAS population that binds weakly to the teratogen, allowing increased circulation of the toxic agent and direct induction of developmental abnormalities in the fetus. However, both groups showed dysregulation in the expression of genes related to the retinoic acid pathway, such as retinoic acid receptor and retinoid X receptor, which are involved in the development, regeneration, and maintenance of the nervous system. These findings highlight the importance of understanding the interplay between alcohol metabolism, the retinoic acid pathway and genetic factors in the development of fetal alcohol syndrome.

The effectiveness of matrix ablation with silver nitrate in the treatment of ingrown toenails. A single-center case-control study.

BACKGROUND: Partial onychectomy with chemical matrixectomy is considered the gold standard treatment for stage II-III ingrown toenails (IT). However, there are scarce reports describing the use of silver nitrate in IT management in adolescents. Our aim is to analyze the effectiveness of matrix ablation with silver nitrate and compare it with partial onychectomy by electrocautery. METHODS: A retrospective study of adolescent patients with stage II-III IT was performed. Those who underwent electrocautery matricectomy in a major outpatient surgical center (Group A) and those who were treated with silver nitrate at an outpatient clinic (Group B) were compared. Efficacy was determined by recurrence and postoperative infection rates. RESULTS: Two hundred and nine patients were included (86 group A; 123 group B), with a total of 382 partial onychectomies (151 group A; 231 group B). Group B patients exhibited a lower recurrence rate (4.7%) when compared to group A (11.2%, p = .02), and had a lower postoperative infection rate (4.0% group A vs. 1.7% group B; p = .18), although not statistically significant. CONCLUSION: Silver nitrate chemical matricectomy after partial onychectomy is an effective treatment for IT in adolescents, with few postoperative complications and low recurrence rate. Therefore, it should be considered as a possible alternative to electrocautery matricectomy.

Does the timing of appendectomy affect outcomes and postoperative complications?

PURPOSE: There is controversy about the necessity of nighttime appendectomy. The aim of this study was to determine whether timing of appendectomy performance plays a role on postoperative complications. METHODS: A retrospective single-center comparative study was performed in children who underwent surgery for acute appendicitis between 2017 and 2021. Patients were divided into groups based on the time slot in which surgery was performed: morning (8:00 h-15:00 h), afternoon (15:00 h-22:00 h) and night (22:00 h-08:00 h). Demographics, intraoperative data, length of hospital stay, and postoperative complications were analyzed and compared. RESULTS: A total of 1643 patients were included: 337 were operated in the morning, 751 in the afternoon and 555 at night. We found no demographic differences. When comparing the intraoperative data, no differences were observed in the percentage of complicated appendicitis. Night group patients presented a higher percentage of open appendectomies (64.5%) when compared to afternoon (49.6%) and morning (46.2%) groups (p < 0.001). Surgery time was also significantly shorter in the night group (45.2 min ± 18.9 min) (p < 0.001). There were no differences in length of hospital stay, postoperative complications rate or readmission rate. CONCLUSION: These results show that in our institution time slot in which the appendectomy is performed has no consequences in postoperative outcomes and complications.

Fetal lung hypoxia and energetic cell failure in the nitrofen-induced congenital diaphragmatic hernia rat model.

PURPOSE: Congenital diaphragmatic hernia (CDH) pathogenesis is poorly understood. We hypothesize that fetal CDH lungs are chronically hypoxic because of lung hypoplasia and tissue compression, affecting the cell bioenergetics as a possible explanation for abnormal lung development. METHODS: To investigate this theory, we conducted a study using the rat nitrofen model of CDH. We evaluated the bioenergetics status using H1 Nuclear magnetic resonance and studied the expression of enzymes involved in energy production, the hypoxia-inducible factor 1α, and the glucose transporter 1. RESULTS: The nitrofen-exposed lungs have increased levels of hypoxia-inducible factor 1α and the main fetal glucose transporter, more evident in the CDH lungs. We also found imbalanced AMP:ATP and ADP:ATP ratios, and a depleted energy cellular charge. Subsequent transcription levels and protein expression of the enzymes involved in bioenergetics confirm the attempt to prevent the energy collapse with the increase in lactate dehydrogenase C, pyruvate dehydrogenase kinase 1 and 2, adenosine monophosphate deaminase, AMP-activated protein kinase, calcium/calmodulin-dependent protein kinase 2, and liver kinase B1, while decreasing ATP synthase. CONCLUSION: Our study suggests that changes in energy production could play a role in CDH pathogenesis. If confirmed in other animal models and humans, this could lead to the development of novel therapies targeting the mitochondria to improve outcomes.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Coccygodynia Due to a Sacrococcygeal Anomaly: A Rare Cause of Constipation.

ABSTRACT: We report a case of an uncommon sacrococcygeal anomaly in a healthy girl initially presenting to the emergency department with coccygodynia and a past history of longstanding constipation. The clinical evolution was satisfactory once the bony anomaly was removed (coccygectomy). This unusual case exemplifies the importance of the medical history and physical examination to make an accurate diagnosis. An inadequate intervention may result in persistent pain, worsening longstanding constipation, and psychosocial and medical consequences.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue.

Epigallocatechin Gallate Ameliorates the Effects of Prenatal Alcohol Exposure in a Fetal Alcohol Spectrum Disorder-Like Mouse Model.

Fetal alcohol spectrum disorder is the main preventable cause of intellectual disability in the Western world. Although binge drinking is the most studied prenatal alcohol exposure pattern, other types of exposure, such as the Mediterranean, are common in specific geographic areas. In this study, we analyze the effects of prenatal alcohol exposure in binge and Mediterranean human drinking patterns on placenta and brain development in C57BL/6J mice. We also assess the impact of prenatal treatment with the epigallocatechin-3-gallate antioxidant in both groups. Study experimental groups for Mediterranean or binge patterns: (1) control; (2) ethanol; (3) ethanol + epigallocatechin-3-gallate. Brain and placental tissue were collected on gestational Day 19. The molecular pathways studied were fetal and placental growth, placental angiogenesis (VEGF-A, PLGF, VEGF-R), oxidative stress (Nrf2), and neurodevelopmental processes including maturation (NeuN, DCX), differentiation (GFAP) and neural plasticity (BDNF). Prenatal alcohol exposure resulted in fetal growth restriction and produced imbalances of placental angiogenic factors. Moreover, prenatal alcohol exposure increased oxidative stress and caused significant alterations in neuronal maturation and astrocyte differentiation. Epigallocatechin-3-gallate therapy ameliorated fetal growth restriction, attenuated alcohol-induced changes in placental angiogenic factors, and partially rescued neuronal nuclear antigen (NeuN), (doublecortin) DCX, and (glial fibrillary acidic protein) GFAP levels. Any alcohol consumption (Mediterranean or binge) during pregnancy may generate a fetal alcohol spectrum disorder phenotype and the consequences may be partially attenuated by a prenatal treatment with epigallocatechin-3-gallate.

Optimum roasting conditions of argan kernels (Argania spinosa L.) for the production of high-quality edible argan oil.

Roasting is an important step in the production of edible argan oils. The effect of argan kernel roasting temperature (ranging from 150 to 200 °C) and time (from 10 to 50 min), on oil yield, contents in total phenolic compounds, α- and γ-tocopherol, and oxidative stability, was researched using response surface methodology. Increases in roasting temperature and time have a significant effect on all the responses. This study showed that the optimum roasting conditions of argan kernel (indirect heat by convection) for the production of edible argan oils were 150 °C and 50 min, which allowed reaching a maximum oil yield of 32.45%. Edible argan oil, obtained under these conditions, had a content of total phenolic compounds of 78.01 mg/kg, α- and γ-tocopherol of 30.28 and 495.03 mg/kg, respectively, and an oxidative stability of 37.58 h. Furthermore, it presented olfactory notes of 'almond, dried fruits, hazelnut and waffle', with 'sweet' and 'fruity' as positive attributes, without any defect.

Abnormal Sonic hedgehog signaling in the lung of rats with esophageal atresia induced by adriamycin.

BACKGROUND: Abnormal lung development was recently described in the rat model of esophageal atresia and tracheoesophageal fistula (EA-TEF). Since in this condition the ventral-to-dorsal switch of Shh expression in the foregut is disturbed, the present study tested the hypothesis that this abnormal expression at the emergence of the tracheobronchial bud might be translated into the developing lung. METHODS: Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle from E7 to E9. Three groups were studied: control and adriamycin-exposed with and without EA-TEF. Embryos were recovered and the lungs were harvested and processed for reverse transcription polymerase chain reaction and immunofluorescence analysis of the Shh signaling cascade. RESULTS: Shh signaling was downregulated at the late embryonic stage of lung development (E13) in embryos with EA-TEF. Throughout the subsequent stages of development, the expression of both Shh and its downstream components increased significantly and remained upregulated throughout gestation. Immunofluorescent localization was consistent with these findings. CONCLUSION: Defective Shh signaling environment in the foregut is present beyond the emergence of lung buds and probably impairs lung development. Later in gestation, lungs exhibited a remarkable ability to upregulate the Shh cascade, suggesting a compensatory response. These findings may be relevant to understand pulmonary disease suffered by children with EA-TEF.

Maternal hyperthyroidism increases the prevalence of foregut atresias in fetal rats exposed to adriamycin.

PURPOSE: Gastrointestinal malformations such as esophageal atresia with tracheoesophageal fistula (EA/TEF) and duodenal atresia (DA) have been reported in infants born to hyperthyroid mothers or with congenital hypothyroidism. The present study aimed to test whether maternal thyroid status during embryonic foregut division has any influence on the prevalence of EA/TEF and DA in an accepted rat model of these malformations. METHODS: Pregnant rats received either vehicle or 1.75 mg/kg i.p. adriamycin on gestational days 7, 8 and 9. Transient maternal hyper or hypothyroidism was induced by oral administration of levothyroxine (LT4, 50 µg/kg/day) or propylthiouracil (PTU, 2 mg/kg/day), respectively, on days 7 to 12 of gestation. Plasma cholesterol, total T3, free T4 and TSH were measured at gestational days 7, 12, and 21. At the end of gestation, the mothers were sacrificed and embryo-fetal mortality was recorded. Fetuses were dissected to determine the prevalence of esophageal and intestinal atresias. RESULTS: At gestational day 12, mothers treated with LT4 or PTU had hyper or hypothyroid status, respectively; plasma cholesterol levels were similar. In the adriamycin-exposed fetuses from hyperthyroid mothers, the embryonal resorption rate and the prevalence of both EA/TEF and DA were significantly higher than in the other groups; maternal hypothyroidism during the same period did not have significant effect on the prevalence of atresias. CONCLUSIONS: Maternal hyperthyroidism during the embryonic window corresponding to foregut cleavage increased the prevalence of both EA/TEF and duodenal atresia in fetal rats exposed to adriamycin. This suggests that maternal thyroid hormone status might be involved in the pathogenesis of foregut atresias and invites further research on this likely clinically relevant issue in humans.

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.

Machine learning algorithms to the early diagnosis of fetal alcohol spectrum disorders.

Introduction: Fetal alcohol spectrum disorders include a variety of physical and neurocognitive disorders caused by prenatal alcohol exposure. Although their overall prevalence is around 0.77%, FASD remains underdiagnosed and little known, partly due to the complexity of their diagnosis, which shares some symptoms with other pathologies such as autism spectrum, depression or hyperactivity disorders. Methods: This study included 73 control and 158 patients diagnosed with FASD. Variables selected were based on IOM classification from 2016, including sociodemographic, clinical, and psychological characteristics. Statistical analysis included Kruskal-Wallis test for quantitative factors, Chi-square test for qualitative variables, and Machine Learning (ML) algorithms for predictions. Results: This study explores the application ML in diagnosing FASD and its subtypes: Fetal Alcohol Syndrome (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND). ML constructed a profile for FASD based on socio-demographic, clinical, and psychological data from children with FASD compared to a control group. Random Forest (RF) model was the most efficient for predicting FASD, achieving the highest metrics in accuracy (0.92), precision (0.96), sensitivity (0.92), F1 Score (0.94), specificity (0.92), and AUC (0.92). For FAS, XGBoost model obtained the highest accuracy (0.94), precision (0.91), sensitivity (0.91), F1 Score (0.91), specificity (0.96), and AUC (0.93). In the case of pFAS, RF model showed its effectiveness, with high levels of accuracy (0.90), precision (0.86), sensitivity (0.96), F1 Score (0.91), specificity (0.83), and AUC (0.90). For ARND, RF model obtained the best levels of accuracy (0.87), precision (0.76), sensitivity (0.93), F1 Score (0.84), specificity (0.83), and AUC (0.88). Our study identified key variables for efficient FASD screening, including traditional clinical characteristics like maternal alcohol consumption, lip-philtrum, microcephaly, height and weight impairment, as well as neuropsychological variables such as the Working Memory Index (WMI), aggressive behavior, IQ, somatic complaints, and depressive problems. Discussion: Our findings emphasize the importance of ML analyses for early diagnoses of FASD, allowing a better understanding of FASD subtypes to potentially improve clinical practice and avoid misdiagnosis.

Abnormal control of lung branching in experimental esophageal atresia.

PURPOSE: Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from abnormal division of the foregut into esophagus and trachea thus, it may influence airway branching and lung development. The present study examined lung morphogenesis in fetuses with EA-TEF focusing in the expression of FGF10 and its receptor FGFR2 IIIb. METHODS: Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle on E7, E8 and E9. Embryos were recovered at E15, E18 and E21 and lungs processed for immunohistochemistry and RT-PCR. Three groups were studied: control, adriamycin-exposed with EA-TEF, and adriamycin-exposed without EA-TEF. Comparisons were performed with Mann-Whitney or t tests (significance level, 5 %). RESULTS: Lung weight at E15 and E18 were significantly lower in adriaEA fetuses in which the relative mRNA levels of FGF10 were significantly higher. These differences disappeared near term. The receptor FGFR2 IIIb messenger was only significantly increased in adria noEA fetuses at E15. Immunohistochemical study was consistent with these findings. CONCLUSIONS: Abnormal expression of FGF10 during earlier stages of development, when the lungs are smaller than controls, suggests a compensatory response aimed at "catching up" delayed tracheobronchial branching. Whether similar changes take place in the human condition and influence respiratory physiology remain to be determined.

Neutrophil-to-lymphocyte ratio as a predictor of postoperative complications and readmissions after appendectomy in children.

To analyze the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the development of postoperative complications and readmission after appendectomy in children. A retrospective single-centered case-control study was conducted on children who underwent appendectomy between 2017 and 2020. Demographics, time since symptoms onset, laboratory tests at admission, postoperative complications, and readmissions in the first 30 days after surgery were recorded. Sensitivity and specificity analysis of the parameters evaluated were determined by the area under the curve (AUC) represented on the receiver operating characteristic (ROC) curves. A total of 1,214 patients (765 males; 449 females) were included, with a median age at diagnosis of 10.4 years. The median time from symptom onset was 24 h. During the first 30 days after surgery, 149 postoperative complications were reported (12.3%). NLR at admission presented the highest AUC (0.753), with a cut-off point of 10.5 for maximum sensitivity (68.7%) and specificity (86.1%). Readmissions were reported in 45 cases (3.7%). NLR at admission presented an AUC of 0.794 significantly higher than neutrophils (0.696), leukocytes (0.654), and time since symptom onset (0.622), making these differences statistically significant (p < 0.001). The cut-off point of NLR > 12.4 was estimated, with a maximum sensitivity and specificity of 71.0% and 82.3% for predicting readmission. NLR is an independent predictor of postoperative complications and readmission in children with acute appendicitis. While its application in routine clinical practice has yet to be established, the NLR may provide clinicians with a tool for identifying high-risk surgical patients.

Intussusception Management in Children: A 15-Year Experience in a Referral Center.

OBJECTIVE: To report a 15-y, single-center experience in the management and outcomes of ileocolic intussusception (ICI) episodes. METHODS: A retrospective study was performed in patients with ICI episodes, who were treated at a single quaternary referral center from 2005 to 2019. Data evaluated included patient demographics, clinical presentation, treatment modalities, hospital stay, complications, and outcomes. RESULTS: A total of 546 ICI episodes (66.1% males) were included, with a median age at diagnosis of 15 mo. Enema reduction was performed in 478 patients (87.6%), with an overall success rate of 85.8%. Hydrostatic saline enema was the most effective method (89.3%) when compared to pneumatic (80.6%) or barium enema (79.8%), this difference being statistically significant (p = 0.031). No associated complications were observed during nonoperative reduction. Surgical treatment was performed in 101 patients, in whom 36 bowel resections were performed. Postoperative complications were reported in 6 patients (5.9%). Hospital stay was significantly longer in patients with operative management (median 5 d vs. 1 d; p < 0.001). CONCLUSIONS: Nonoperative management has a high overall success rate and low complication and recurrence rates. Saline enema reduction presents the highest effectiveness, and should be considered the first-line treatment.

The role of the neutrophil-to-lymphocyte ratio in avoiding negative appendectomies.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory biomarker that is easily calculated with data from the differential white blood cell count. The aim of our study was to analyse the role of the NLR in the detection of negative appendectomies and to compare its usefulness with other clinical, sonographic and laboratory factors previously described. METHODS: We conducted a retrospective study in patients aged less than 16 years who underwent appendectomy in our hospital between 2017 and 2020. We divided patients into 2 groups based on appendiceal histological findings: NA group (negative appendicitis: absence of appendiceal inflammation) and PA group (positive appendicitis: presence of inflammation in any layer of the appendiceal wall). We analysed demographic, clinical, sonographic and laboratory characteristics. RESULTS: We included a total of 1269 patients, 1244 in the PA group and 25 in the NA group, with no differences between groups in demographic characteristics. The proportion of patients that presented with nausea and vomiting was significantly smaller in the NA group compared to the PA group (P < .001), and there were no other differences in symptoms. The appendiceal diameter on ultrasound was significantly smaller in the NA group (8.1 ±â€¯2.1 vs. 9.7 ±â€¯2.8 mm; P < .001). The white blood cell and neutrophil counts and the NLR were significantly higher in the PA group (P < .001), as was the level of C-reactive protein (18.6 vs. 2.6; P = .005). The ROC curve analysis revealed that the NLR was the parameter with the highest AUC (0.879) for the diagnosis of negative appendicitis, with a cut-off point of 2.65 for a maximum sensitivity of 84.2% and specificity of 83.8%. CONCLUSION: The NLR is the preoperative parameter that best discriminates patients without acute appendicitis. Values of less than 2.65 should make clinicians contemplate diagnoses other than appendicitis.

Iatrogenic Neonatal Esophageal Perforation: A European Multicentre Review on Management and Outcomes.

BACKGROUND: The aim of this multicenter retrospective study and literature review was to review management and outcomes of neonatal esophageal perforation (NEP). METHODS: Protocol data were collected from four European Centers on gestational age, factors surrounding feeding tube insertion, management and outcomes. RESULTS: The 5-year study period (2014-2018) identified eight neonates with median gestational age of 26 + 4 weeks (23 + 4-39) and median birth weight 636 g (511-3500). All patients had NEP from enterogastric tube insertions, with the perforation occurring at median 1st day of life (range 0-25). Seven/eight patients were ventilated (two/seven-high frequency oscillation). NEP became apparent on first tube placement (n = 1), first change (n = 5), and after multiple changes (n = 2). Site of perforation was known in six (distal n = 3, proximal n = 2 and middle n = 1). Diagnosis was established by respiratory distress (n = 4), respiratory distress and sepsis (n = 2) and post-insertion chest X-ray (n = 2). Management in all patients included antibiotics and parenteral nutrition with two/eight receiving steroids and ranitidine, one/eight steroids only and one/eight ranitidine only. One neonate had a gastrostomy inserted, while in another an enterogastric tube was orally successfully re-inserted. Two neonates developed pleural effusion and/or mediastinal abscess requiring chest tube. Three neonates had significant morbidities (related to prematurity) and there was one death 10 days post-perforation (related to prematurity complications). CONCLUSIONS: NEP during NGT insertion is rare even in premature infants after evaluating data from four tertiary centers and reviewing the literature. In this small cohort, conservative management seems to be safe. A larger sample size will be necessary to answer questions on efficacy of antibiotics, antacids and NGT re-insertion time frame in NEP.

Neutrophil-to-Lymphocyte Ratio as a Predictor of the Need for Surgical Treatment in Children's Intussusception.

OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR) is an emerging inflammatory marker in abdominal pathologies. Ileocolic intussusception (ICI) involves a progressive intestinal inflammation, and the effectiveness of nonsurgical treatment (enema) might be related to the inflammation degree, although no previous studies have investigated this relationship. Our aim is to identify predictors of the need for surgical treatment in ICI. MATERIALS AND METHODS: A single-center, retrospective, case-control study was performed in children with ICI, who were treated with initial nonsurgical management between 2005 and 2019. Patients were divided in two groups: A (effective enema) and B (need for surgery). Admission demographic and clinical and laboratory data were analyzed. Specificity and sensitivity of the different parameters as predictors of the need for surgical treatment were determined by receiver operating characteristic (ROC) curves. RESULTS: A total of 511 patients were included (410: group A; 101: group B), without statistically significant demographic differences. Group B presented significantly higher frequency of vomiting, bloody stools, and longer median time since symptoms onset (24 vs. 8 hours; p < 0.001). Group B presented higher median laboratory inflammatory markers than group A: NLR (6.8 vs. 1.8; p < 0.001), neutrophils (10,148 vs. 7,468; p < 0.001), and C-reactive protein (CRP; 28.2 vs. 4.7; p < 0.001). In ROC curve analysis, NLR had an area under the curve of 0.925, higher than neutrophil count (0.776; p = 0.001), CRP (0.670; p = 0.001), and time since symptoms onset (0.673; p = 0.001). It was estimated a cut-off point of NLR greater than 4.52 (sensitivity: 73.2%; specificity: 94.5%). CONCLUSION: High NLR values imply a high degree of bowel inflammation and might anticipate the need for surgical treatment in ICI in children. LEVEL OF EVIDENCE: III.