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Purpose: We performed a retrospective study to determine the effectiveness and feasibility of articulating linear stapler in laparoscopic total splenectomy (LTS) and laparoscopic partial splenectomy (LPS), focusing on technical laparoscopic skills that could help pediatric surgeons to avoid intra- and postoperative complications. Methods: Retrospective cohort study of children younger than 18 years who underwent laparoscopic spleen surgery between January 2008 and March 2020. Age, sex, indication for surgery, operative time (OT), intra- and postoperative complications, and postoperative length of hospital stay (LHS) were analyzed. Data from parenchymal resection and vessels sealing techniques were obtained. Results: Thirty patients, 19 LTS and 11 LPS, were included. The mean age of the patients was 10.9 years, and 16 patients were male and 14 were female. For hematologic diseases, LTS was the elective surgery, associated with cholecystectomy in 5 cases. LPS was the common procedure for splenic cysts. The stapler was used in LTS to close the hilum vessels and in LPS for parenchymal resection. No statistically significant differences in OT were observed comparing LTS and LPS. Two conversions occurred in LTS; none in LPS. The mean LHS was 6 days in both groups. No recurrence or major complications appeared in both groups at 1-12 years of follow-up. In particular for LPS, there are no relapse of cyst neither reduction in splenic function. Conclusions: This study shows the effectiveness, feasibility, and safety of mechanic stapler in splenic surgery both for hilum vessels sealing and for parenchymal resection. The use of this device can reduce risk of hemorrhagic recurrences or major surgical complications improving the safety of the operation.

Purpose COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. Methods We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019–January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. Results Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8–13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. Conclusions A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children’s health and help delineate long term follow-up management and prognosis.

Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmedWe recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively.adiponectin and kisspeptin levels were significantly different into groups (IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.

Background: Amniotic band sequence (ABS) is a rare congenital disorder resulting from the entanglement of fetal parts by fibrous bands that may cause disruptions, deformations, or malformations that can range from mild to life threatening conditions. Prenatal diagnosis is usually based on ultrasounds visualization on amniotic bands attached to fetal parts, possibly causing fetal defects. Case Presentation: A 19-year-old woman with an unremarkable clinical history and a low-risk pregnancy was referred to our Fetal Therapy Unit for a suspected fetal clubfoot at 22 weeks gestational age. A chorioamniotic separation, together with unilateral clubfoot was diagnosed. Due to a high risk of premature rupture of membranes a decision was made not to perform amniocentesis for genetic investigation. At prenatal follow up progressive polyhydramnios developed with a preterm spontaneous rupture of the membranes at 34 weeks. After caesarean section – due to breech presentation – an amniotic band was observed at the abdominal level causing a circular skin lesion, constriction, and a sub-occlusive intestinal status. Moreover, a left clubfoot with amputation of distal phalanx of the second toe and a right foot amputation of 2nd and 3rd toes were evident. The neonate underwent abdominal plastic surgery on the second day of life with complete recovery. Following the postnatal diagnosis of ABS, we re-examined a stored fetal 3D ultrasound volume acquired at 22 weeks and, focusing on the fetal surface rendering, we could notice the deep abdominal skin furrow that was evident at birth. Discussion: This case represents an unusual antenatal presentation of an amniotic band sequence that escaped prenatal diagnosis with a progressive polyhydramnios as an indirect sign of fetal bowel obstruction caused by an abdominal constricting band. In the presence of chorioamniotic separation and additional ominous ultrasound findings, it is advisable to consider the possibility of an ABS.

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway, this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2, on the contrary, they maintain their staminality profile.

Background Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. Results We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”. Conclusions In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.

Children with intellectual disability/neurodevelopmental delay (ID-ND) commonly ingest foreign bodies (FB) and often present complications due to peculiar aspects of their condition. The aim of this paper is to report the experience of two centers in the management of ID-ND patients after FB ingestion and to discuss a possible algorithm for clinical practice. We retrospectively evaluated data of patients managed for FB ingestion (period: 2017–2021), focusing on those with ID-ND, specifically demographics and baseline diagnosis, elements related to the event, symptoms, time to endoscopy, FB location, endoscopic details, and follow-up. A total of 457 patients were managed in the study period and 19 had ID-ND (mean age 9.8 ± 3.5 years, 15 males). A total of 16/19 (84.2%) were symptomatic and required an operative approach. Recurrent ingestions and multiple FB were found in 2 and 11 patients, respectively. Endoscopy (mean time 65.6 ± 41 min) was effective in 14 cases (73.6%) and 6 patients (31.6%) developed a complication. FB ingestion in ID-ND patients represents a challenging condition for the clinician and a potentially dangerous situation. It should be addressed specifically by a multidisciplinary team considering a tailored diagnostic and management protocol.

Background: Over the last 30 years, the incidence of pediatric urolithiasis (PU) has been increasing and the surgical management has evolved toward a minimally invasive approach (MIA). We reported the experience of two Centers of Pediatric Surgery in the management of PU, focusing on MIA as first choice in treatment. Methods: Data were retrospectively analyzed from October 2009 to October 2019 in children with urolithiasis who were admitted to two referral Italian Centers of Pediatric Surgery. Demographic and clinical data of the patients, features of the urolithiasis, type of surgery were considered. Results: Seventy patients (7.3 ± 5.0 years) with normal renal function were treated for calculi in the pyelocaliceal system (45.7%), ureter (34.3%), bladder (4.3%), urethra (1.4%), and multiple locations (14.3%). Size of calculi was >10 mm in 55.7% of cases (kidney>bladder/urethra>multiple>ureter, p = 0.01). Symptoms were present in 75.7% of patients. Family history was positive in 16.9% of cases. MIA was performed in 59 patients (84.3%): 11.8% shockwave lithotripsy (kidney>ureter>multiple); 32.2% ureteral retrograde surgery (ureteral>other localizations); 30.5% retrograde intrarenal surgery (kidney>other localizations); and 25.4% other procedures including percutaneous nephrolithotomy, cystoscopic bladder stone removal or laser cystolithotripsy (kidney>bladder>multiple). Preoperative stenting was necessary in 52.8% of cases. Four MIA procedures (6.9%, kidney>ureter/multiple) were converted to open surgery. Open surgery was required as first approach in 15.7% of patients (kidney>ureter>multiple) who needed urgent surgery or had associated congenital renal anomalies. In 18/70 of children (25.7%), with prevalence of stones in kidney and multiple location (p < 0.01), a second procedure completed the treatment (88.8% MIA). Intraoperative difficulties were recorded in 8.5% of cases, without difference between location and size of calculi. Late complications (5.7%) were related to displacement and infection of the ureteral stent. Conclusions: MIA resulted to be feasible in more than 75% of primary surgery and in more than 85% of cases requiring a second procedure. Preoperative stent was mandatory in more than 50% of children. The technological evolution allowed to overcome many of the technical difficulties related to the approach to the papilla and lower calyxes. Open surgery is reserved for selected cases and endoscopic surgery represents the best choice of treatment for PU.

The explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G0 cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, and proliferative growth of tumor MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell cycle phase. Healthy donor bone marrow-derived mesenchymal stromal cells (BM-MSCs) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor MSCs. All BM-MSCs expressed the typical DNA profile of proliferating cells, while in all tumor MSC samples, ≥70% of the cells were detected in the G0/G1 phase. In particular, seven tumor MSC samples displayed intermediate cell cycle behavior, and the other seven tumor MSC samples exhibited a slow cell cycle. The increased number of tumor MSCs in the G0–G1 phase compared with BM-MSCs supports a role for quiescent MSCs in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential in identifying predictive markers of recurrence and to promote a dedicated surgical planning.

Background: Few studies have been carried out with the aim of describing the clinical course and follow-up of patients with tracheomalacia. We aim to describe the symptoms at diagnosis and the post-treatment clinical course of patients affected by airway malacia. Methods: We retrospectively analyzed characteristics of pediatric patients with a diagnosis of airway malacia. Patients were classified into three groups: bronchomalacia (BM), tracheomalacia (TM) and tracheo-bronchomalacia (TBM). Demographic and clinical data, diagnostic work-up and surgical treatment were recorded. Results: 13/42 patients were affected by congenital syndromes (30.9%). Esophageal atresia with or without tracheal-esophageal fistula (EA/TEF) was detected in 7/42 patients (16.7%). Cardiovascular anomalies were found in 9/42 (21.4%) and idiopathic forms in 13/42 (30.9%). BM occurred in 7/42 (16.6%), TM in 23/42 (54.7%) and TBM in 12/42 (28.6%). At the diagnosis stage, a chronic cough was reported in 50% of cases with a higher prevalence in EA/TEF (p = 0.005). Surgery was performed in 16/42 (40%) of children. A chronic cough and acute respiratory failure were correlated to the need for surgery. During follow-up, there was no difference in persistence of symptoms between conservative vs surgical treatment (p = 0.47). Conclusion: the management of tracheomalacia remains a challenge for pediatricians. Clinical manifestations, such as a barking cough and acute respiratory failure may suggest the need for surgery. Follow-up is crucial, especially in those patients affected by comorbidities, so as to be able to manage effectively the possible persistence of symptoms, including those that may continue after surgical treatment.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Background Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+ /CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

Hemodynamic changes during laparoscopy have not been well defined in very young children. In this study, intraoperative monitoring of hemodynamic parameters and oxygenation was evaluated during laparoscopy in infants weighing

Background and purpose of the study: Esophageal atresia (AE) is a congenital anomaly that affects the normal development of the esophagus in neonates. The timely surgical approach allows its resolution, but long-term morbidities in adolescents show neurological developmental abnormalities and musculoskeletal deformities. The goal in this preliminary study is to investigate the recovery of the range of the right upper limb movement and on the rise of the anthropometric parameters through the osteopathic manipulative treatment, which, by acting on the connective system has a trophotropic effect documented. Materials and Methods: 5 children with type III AE were included in the study. 6 OMTs were performed in 4 months. At each treatment, the following were assessed height, weight, BMI and ROM in elevation of the right upper limb. OMT has been applied to improve scar, larynx, rib cage, and sternum mobility. Results: in the statural growth there was an average change of 2.3 cm in 4 months and in the ROM of the upper limb there was an average increase of 8° in 4 months. There were no significant changes in weight and BMI. Conclusions: This preliminary study suggests that it is a viable option to be further researched. In addition, the study provides potentially valuable evidence that the osteopathic manipulative treatment could benefit the increase in anthropometric parameters and the mobility of the right upper limb of children operated on for AE. In light of the results, new studies to evaluate the effectiveness of OMT in post surgical treatment of congenital malformations of the thorax can be considered in the future.

Considerable reorganization of the regional network for pediatric burn treatment during the pandemic was required to cope with severe burn injuries in small children. In support of the emergency network for burns during the COVID-19 pandemic, we referred to regional indications for centralization in our hospital for all children aged less than 5 years who presented with severe burns, &gt, 15% of total body surface area (TBSA), or who necessitated admittance to the pediatric intensive care unit (PICU). A new service with a dedicated management protocol was set up to treat pediatric burns in our SARS-CoV-2 pediatric hospital during the lockdown period. A multidisciplinary burn treatment team was set up to offer compassionate and comprehensive burn care. Patient’s clinical data, burn features, treatment and follow up were recorded. A higher number of admissions was recorded from February to December 2020 compared with the same period in 2019 (52 vs. 32 admissions). Eighteen patients were admitted to the COVID-19 Service (10 M/8 F, 3.10 ± 2.6 yrs), ten children (55.5%) were hospitalized in the ward and eight in the ICU (44.5%). Fifty percent of the cases presented with lesions extending over &gt, 15% TBSA, in one case, TBSA was 35%. All patients suffered 2nd-degree burns, while five patients also had 3rd degree lesions covering more than 15% TBSA. All of the injuries occurred at home. No major secondary infections were recorded. Successful treatment was achieved in 94.4% of cases. The average length of stay was 15.2 ± 12.6 days. A proactive, carefully planned service, involving a multidisciplinary team, was created to ensure appropriate care in a pediatric hospital during the COVID-19 period, despite the effective pandemic associated challenges. Better health promotion in pediatric burn cases should also include dedicated TBSA assessment and a database of children’s burn characteristics.

Pediatric obesity is a multifaceted disease that can impact physical and mental health. It is a complex condition that interweaves biological, developmental, environmental, behavioral, and genetic factors. In most cases lifestyle and behavioral modification as well as medical treatment led to poor short-term weight reduction and long-term failure. Thus, bariatric surgery should be considered in adolescents with moderate to severe obesity who have previously participated in lifestyle interventions with unsuccessful outcomes. In particular, laparoscopic sleeve gastrectomy is considered the most commonly performed bariatric surgery worldwide. The procedure is safe and feasible. The efficacy of this weight loss surgical procedure has been demonstrated in pediatric age. Nevertheless, there are barriers at the patient, provider, and health system levels, to be removed. First and foremost, more efforts must be made to prevent decline in nutritional status that is frequent after bariatric surgery, and to avoid inadequate weight loss and weight regain, ensuring successful long-term treatment and allowing healthy growth. In this narrative review, we considered the rationale behind surgical treatment options, outcomes, and clinical indications in adolescents with severe obesity, focusing on LSG, nutritional management, and resolution of metabolic comorbidities.

Background: The prevalence of pediatric metabolic syndrome is usually closely linked to overweight and obesity, however, this condition has also been described in children with disabilities. We performed a multivariate pattern analysis of metabolic profiles in neurologically impaired children and adolescents in order to reveal patterns and crucial biomarkers among highly interrelated variables. Patients and methods: We retrospectively reviewed 44 cases of patients (25M/19F, mean age 12.9 ± 8.0) with severe disabilities. Clinical and anthropometric parameters, body composition, blood pressure, and metabolic and endocrinological assessment (fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, gamma-glutamyl transpeptidase) were recorded in all patients. As a control group, we evaluated 120 healthy children and adolescents (61M/59F, mean age 12.9 ± 2.7). Results: In the univariate analysis, the children-with-disabilities group showed a more dispersed distribution, thus with higher variability of the features related to glucose metabolism and insulin resistance (IR) compared to the healthy controls. The principal component (PC1), which emerged from the PC analysis conducted on the merged dataset and characterized by these variables, was crucial in describing the differences between the children-with-disabilities group and controls. Conclusion: Children and adolescents with disabilities displayed a different metabolic profile compared to controls. Metabolic syndrome (MetS), particularly glucose metabolism and IR, is a crucial point to consider in the treatment and care of this fragile pediatric population. Early detection of the interrelated variables and intervention on these modifiable risk factors for metabolic disturbances play a central role in pediatric health and life expectancy in patients with a severe disability.

Introduction: The presentation of eosinophilic myenteric ganglionitis (EMG) can be similar to that of Hirschsprung's disease (HD). In a limited number of cases of pediatric patients, the diagnosis of both EMG and HD are reported. A case of pseudo-obstruction in EMG occurring in a child with HD diagnosis is discussed with literature review.Case Presentation: A boy aged 2 years and 6 months presented with intractable constipation and abdominal distension. Histological HD diagnosis was carried out and transanal Soave pullthrough was performed. At the age of 3 years and 2 months, an infectious enterocolitis occurred. One month later, he presented with constipation, marked abdominal distension and melena. Full thickness colonic biopsies revealed eosinophilic myenteric ganglionitis. Specific IgE tests were positive for several foods. Dietary exclusion was adopted with resolution of clinical symptoms and histologic remission.Conclusion: EMD may occur in patients with HD. At the onset, EMD may be associated with functional intestinal obstruction. The use of an elimination diet proved effective for the relief of symptoms. Long term follow-up is mandatory to define the timing of the reintroduction of foods.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the routine activities of pediatric surgical centers, and it determined the reduction of admissions in the pediatric emergency departments (PED). We reviewed the records of patients affected by acute appendicitis (AA) during the COVID-19 pandemic period in a large Italian COVID-19 pandemic area.Methods: Data regarding demographics, age, macroscopic and microscopic findings, and time between symptom onset and PED admission of patients affected by confirmed AA in the period between March and April 2020 were considered. The data were compared with those obtained during the same period of 2019, 2018, and 2017 in the included centers. Data were quoted as median (range) or absolute number. Non-parametric statistical tests were used to compare groups. A p ≤ 0.05 was regarded as significant. Since only anonymous data have been used and the data storage meets current data protection regulations, ethical committee approval was not required for this study.Results: Eighty-six patients underwent surgical appendectomy for AA between February 20th, 2020 and April 20th, 2020; 32.5% were complicated appendicitis and 67.5% were uncomplicated. Fifty-three patients were males and 33 were females. Patients' age ranged from 3 to 17 years and the median age was 10 years. The median time between the onset of symptoms and the admission in PED was 1.85 days. The average time between the symptom onset and PED admission was 1.8 days.Conclusions: Although fear from the COVID-19 pandemic determined a delayed diagnosis of serious pediatric diseases, the increasing prevalence and severity of AA were not demonstrated in the most COVID-19-affected areas of Italy.

Background: Gastro-esophageal reflux disease (GERD), requiring surgical correction, and nutritional problems are reported after long-gap esophageal atresia (LGEA) repair and might jeopardize the postoperative course in some babies. We report an exploratory evaluation of the role of transgastric jejunostomy (TGJ) as a temporary nutritional tool before surgery for GERD in LGEA. Methods: Seven infant patients operated on for LGEA with intra-thoracic gastro-esophageal junction (GEJ) and growth failure, requiring improvement in their nutritional profile in anticipation of surgery, were retrospectively evaluated. Post-surgical follow-up, including growth evolution, complications, and parental quality of life (QoL), were considered. Results: The TGJ was placed at a mean age of 8.6 &plusmn, 5.6 months. The procedure was uneventful and well-tolerated in all seven cases. At 6.6 &plusmn, 2.0 months after TGJ placement, significant weight gain (weight z-score &minus, 2.68 &plusmn, 0.8 vs &minus, 0.9 &plusmn, 0.2, p &lt, 0.001) was recorded, allowing the GERD surgery to proceed. A significant difference in hospital admissions between 3 months before and post-TGJ insertion was noted (4.8 &plusmn, 0.75 vs. 1.6 &plusmn, 0.52, p &lt, 0.01). A significant amelioration of QoL after TGJ placement was also recorded, in particular, the biggest improvements were related to parents&rsquo, perceptions of the general health and emotional state of their babies (p &lt, 0.001). Conclusions: The placement of TGJ as a temporary nutritional tool in selected cases of LGEA could improve nutritional conditions and parental QoL before fundoplication, allowing successful surgical treatment of GERD to be carried out.

Background: High resolution manometry (HRM), has been recently introduced in clinical practice to detect esophageal intraluminal pressure and esophageal motor function. We evaluated the feasibility and usefulness of intraoperative esophageal HRM during antireflux laparoscopic procedures in pediatric cases with neurological impairment (NI) or esophageal atresia (EA). Methods: From January to November 2019, seven children (5 NI, 2 EA) with gastroesophageal reflux (GER) were enrolled. Data on intraoperative pressure changes of the esophagogastric junction (EGJ) and postoperative follow-up data were collected. Results: Average preoperative LES pressures were not significantly different from postoperative pressures. A sliding hernia was detected in all patients as evidenced by EGJ double peak pressures. Hernia correction after esophageal traction was complete in 71.4% of the patients, and residual hernia (&lt, 2 cm) was detected in 28.6%. Postoperative EGJ pressures were higher compared to preoperative sphincteric pressures (p &lt, 0.001), in NI patients, higher postoperative values were noted compared to EA (p = 0.05). No sliding hernia and/or GER relapses were recorded. Two patients reported dysphagia postoperatively. Conclusions: Intraoperative HRM may optimize esophageal pressure changes during laparoscopic fundoplication. Further studies are needed to confirm the usefulness of a tailored surgical approach to reduce postoperative complications.

This Special Issue aims to examine the crucial role of nutritional status starting from pregnancy in modulating fetal, neonatal and infant growth and metabolic pathways, with potential long-term impacts on adult health. Poor maternal nutritional conditions in the earliest stages of life during fetal development and early life may induce both short-term and longer lasting effects; in particular, an increased risk of noncommunicable diseases (NCDs) and other chronic diseases such as obesity, which itself is a major risk factor for NCDs, is observed over the lifespan. Poor maternal nutrition affects the fetal developmental schedule, leading to irreversible changes and slowdown in growth. The fetus limits its size to conserve the little energy available for cardiac functions and neuronal development. The organism will retain memory of the early insult, and the adaptive response will result in pathology later on. Epigenetics may contribute to disease manifestation affecting developmental programming. After birth, even though there is a limited evidence base suggesting a relationship between breastfeeding, timing and type of foods used in weaning with disease later in life, nutritional surveillance is also mandatory in infants in the first year of life. We will explore the latest findings on nutrition in early life and term and preterm babies, as well as the role of malnutrition in the short- and long-term impact over the lifespan. Focusing on nutritional interventions represents part of an integrated life-cycle approach to prevent communicable and non-communicable diseases.

Background: Long-term negative sequelae of esophageal atresia (EA) may induce poor growth and impaired nutritional status in childhood. We describe the nutritional profile and energy metabolism of children with repaired EA to identify malnutrition risk factors and optimize growth management. Methods: Twenty-one children (&gt, 4 years) were included, and anthropometric measurements, nutritional assessment, and energy metabolism were considered. The subjects were defined as undernourished if they met BMI &lt, &minus, 2 standard deviation (SD). To grade undernutrition, we defined the prevalence of underweight, stunting, and wasting (cut-off level of &lt, 2 SD). Medical records were reviewed for the type of EA and surgery and perinatal data. Results: Malnutrition was detected in 28.6% of children. Underweight was detected in 23.8% of patients (all with undernutrition p &lt, 0.01). Wasting was noted in 28.6% of patients, of these 5 children were undernourished (p &lt, 0.001) and stunting was noticed in only one patient with malnutrition (p = 0.5). Resting expenditure energy (REE) was lower in undernourished subjects compared to subjects with adequate nutritional status (p &lt, 0.001). Malnutrition was associated to: type of EA (p = 0.003, particularly type A and C), intervention including deferred anastomosis due to long-gap repair (p = 0.04) with/or without jejunostomy (p = 0.02), gastric pull-up (p = 0.04), primary anastomosis (p = 0.04), pyloromyotomy in long-gap (p &lt, 0.01), small for gestational age condition (p = 0.001). Conclusions: undernutrition risk factors, beyond the type of malformation, surgery, and perinatal factors, must be early considered to personalize nutritional programming. Energy metabolism is important to monitor the nutritional requirements. The management of nutritional issues is surely a contributory factor able to counteract the poor growth of children with EA.

Introduction: The advantages of the robotic approach in surgery are undisputed. However, during surgical training, how this technique influences the learning curve has not been described. We provide a tentative model for analyzing the learning curves associated with observation and active participation in learning different surgical techniques, using functional imaging. Methods: Forty medical students were enrolled and assigned to 4 groups who underwent training in robotic (ROB), laparoscopic (LAP), or open (OPEN) surgery, and a control group that performed motor training without surgical instruments. Surgical/motor training included six 1-h sessions completed over 6 days of the same week. All subjects underwent functional magnetic resonance imaging (fMRI) scanning sessions, before and after surgical training during. Results: Twenty-three participants completed the study. The 3 surgical groups exhibited different learning curves during training. The main effects of the day of training (p < 0.01) and the group (p < 0.01) as well as a significant interaction of day of training group (p < 0.01) were observed. The performance increased in the first 4 days, reaching a peak at day 4, when all groups were considered together. The OPEN group showed the best performance compared to all other groups (p < 0.04). The OPEN group showed a rapid improvement in performance, which peaked at day 4 and decreased on the last day. Similarly, the LAP group showed a steady increase in the number of exercises they completed, which continued for the entire training period and reached a peak on the last day. However, the participants training in ROB surgery, after a performance initially indistinguishable from that of the LAP group, had a dip in their performance, quickly followed by an improvement and reaching a plateau on day 4. fMRI analysis documented the different involvement of the cortical and subcortical areas based on the type of training. Surgical training modified the activation of some brain regions during both observation and the execution of tasks. Conclusions: Differences in the learning curves of the 3 surgical groups were noted. Functional brain activity represents an interesting starting point to guide training programs.

Obesity is a growing health problem in both children and adults, impairing physical and mental state and impacting health care system costs in both developed and developing countries. It is well-known that individuals with excessive weight gain frequently develop obesity-related complications, which are mainly known as Non-Communicable Diseases (NCDs), including cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver disease, hypertension, hyperlipidemia and many other risk factors proven to be associated with chronic inflammation, causing disability and reduced life expectancy. This review aims to present and discuss complications related to inflammation in pediatric obesity, the critical role of nutrition and diet in obesity-comorbidity prevention and treatment, and the impact of lifestyle. Appropriate early dietary intervention for the management of pediatric overweight and obesity is recommended for overall healthy growth and prevention of comorbidities in adulthood.

Recent developments in endovascular radiological techniques and devices have rendered embolization a major therapeutic option prior to surgery in many renal vascular or neoplastic diseases. A 19-yearold female patient, with a diagnosis of tuberous sclerosis complex (TSC) in childhood, was admitted with severe anemia. Polycystic kidney disease in end-stage renal failure appeared four years before and the patient has been undergoing peritoneal dialysis. The patient’s medical history also included bilateral renal angiomyolipomas (AMLs). One year earlier, a unilateral endovascular embolization was performed to repair a bleeding aneurysm at the right renal upper pole. A second bilateral ruptured renal aneurysm was diagnosed at admission. To continue with peritoneal dialysis and prevent intrarenal hemorrhage and intraperitonal bleeding, an urgent bilateral renal AE was performed. Two months later she underwent a bilateral retroperitoneal nephrectomy. The posterior surgical approach, preserved the peritoneal surface area and adequate conditions to continue dialysis. At histology, bilateral AMLs were confirmed and a renal cell carcinoma of the right kidney was concurrently discovered. She undergoes continuous peritoneal dialysis. Urgent selective renal AE represents a feasible treatment for bilateral AML bleeding. It is safe and feasible before performing nephrectomy in patients with end-stage renal failure.

Background: Laparoscopic cholecystectomy (LC) is the standard of care for gallbladder (GB) pathologies. We evaluated clinical, ultrasonographic (US) data as well as histopathological findings in children affected with symptomatic cholecystic disease (SCD) who underwent LC, with the aim of defining surgical timing.Methods: We reviewed our cases who underwent elective LC (ELC) or urgent LC (ULC). Clinical, US, surgical and histological features were used to create different risk scores.Results: We considered 26 children (17 ELC/9 ULC). US signs were not different in the two groups (p > 0.05). Operating times were longer in ELC than in ULC (p = 0.01). Histopathological evaluation revealed fibrosis and atrophy in both ELC and ULC. The clinical risk score was higher in ELC compared to ULC (p < 0.001). An increased operative risk score was noted in patients with systemic inflammatory signs (OR1.98), lithotherapy (OR1.4.3) and wall thickening ≥3 mm (OR2.6). An increased histopathological risk score was detected in children with symptom duration >7 days (OR3.61), concomitant hematological disease (OR1.23) and lithotherapy (OR3.61).Conclusion: Criteria adopted in adults cannot be adopted to detect the severity of GB damage in children. A dedicated clinical and US score is mandatory to define the most appropriate surgical timing.

Hypoxia is a common form of intrauterine stress characterized by exposure to low oxygen concentrations. Gestational hypoxia is associated with the generation of reactive oxygen species. Increase in oxidative stress is responsible for damage to proteins, lipids and DNA with consequent impairment of normal cellular functions. The purpose of this review is to propose a summary of preclinical and clinical evidences designed to outline the correlation between fetal hypoxia and oxidative stress. The results of the studies described show that increases of oxidative stress in the placenta is responsible for changes in fetal development. Specifically, oxidative stress plays a key role in vascular, cardiac and neurological disease and reproductive function dysfunctions. Moreover, the different finding suggests that the prenatal hypoxia-induced oxidative stress is associated with pregnancy complications, responsible for changes in fetal programming. In this way, fetal hypoxia predisposes the offspring to congenital anomalies and chronic diseases in future life. Several antioxidant agents, such as melatonin, erythropoietin, vitamin C, resveratrol and hydrogen, shown potential protective effects in prenatal hypoxia. However, future investigations will be needed to allow the implementation of these antioxidants in clinical practice for the promotion of health in early intrauterine life, in fetuses and children.

During the coronavirus disease of 2019 (COVID-19) emergency, in the pediatric surgical setting, it has been essential to avoid and contain infections as well as to protect both the patients and the surgical team. During this emergency, procedures and workflow were adapted to provide the safest possible environment for both the surgical team and the patients. Pediatric surgical activities were reorganized during the COVID-19 pandemic at the “Vittore Buzzi” Children’s Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), Italy. Resources were optimized in order to maintain high levels of care and quality of assistance. During the COVID-19 emergency, the pediatric surgical department at the “Vittore Buzzi” Children’s Hospital became an acute care surgical service. For the reorganization of surgical activities, institutional protocols were adapted in order to preserve the pediatric-specific characteristics of our service; five crucial points were specifically addressed. The pediatric surgical procedures carried out during the initial two months of the Italian lockdown are also reported. Continuity of care was maintained for children affected by severe diseases, such as tumors and neurosurgical conditions, whose treatment could not be deferred. Telemedicine and telecommunication were adopted as quick-support modalities for pre- and post-operative care. This reorganization allowed us to preserve the “pediatric specificity” and all care-related procedures offered at this high-quality/high-volume surgical care referral center.

Objectives The coexistence of celiac disease (CD) and obesity/overweight is not unusual. We investigate the prevalence and clinical presentation of CD, detected by screening, among children with excessive weight gain. Methods We enrolled 200 children referred for overweight/obesity to our outpatient clinic. Medical history during pregnancy and childhood and lifestyle variables were recorded. Patients were screened for CD with total immunoglobulin A (IgA), IgA anti-transglutaminase (tTG-IgA) and IgA anti-endomysial antibodies (EMA-IgA). In subjects with positive autoantibodies, esophagogastroduodenoscopy (EGDS) was performed and genetic testing for HLA DQ2 and/or DQ8 haplotypes was tested. Results CD positive antibodies (tTg-IgA and EMA-IgA) were detected in eight patients (4%); in all subjects CD diagnosis was confirmed by HLA-DQ2 and/or DQ8 compatibility and EGDS. No association between CD and medical history during pregnancy and childhood or lifestyle variables was noted; however, a dietary difference was identified with those testing positive for CD also reporting a lower weekly consumption of fruits and vegetables (p=0.04). Headache was reported more frequently in patients with than without CD (p=0.04). Familiar positivity for autoimmune diseases was revealed in CD patients (p=0.01). Conclusion CD should be considered in children with excessive weight gain. Familial predisposition to other autoimmune diseases may represent a risk factor for development of CD. Even though the relationship between headache and CD is not well defined, the patients with headache of unknown origin should be screened for CD.

Background: Pediatric robot-assisted surgery (RAS) is gaining increasing acceptance. We aimed to assess the diffusion of pediatric RAS in Italy, the training period, indications, preliminary outcom...

Objectives Data on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing. Patients and methods We retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP. Results Basal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p Conclusion Despite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

Minimally invasive surgery (MIS) is widely utilized across multiple surgical disciplines, including gynecology. To date, laparoscopy is considered a common surgical modality in children and adolescents to treat gynecological conditions. Robotic surgical devices were developed to circumvent the limitations of laparoscopy and have expanded the surgical armamentarium with better magnification, dexterity enhanced articulating instruments with 5-7 degrees of freedom, and ability to scale motion thus eliminating physiologic tremor. There are well-documented advantages of MIS over laparotomy, including decreased post-operative pain, shorter recovery times, and better cosmetic results. Indications for MIS in pediatric gynecology are reported in this review and technical considerations are described to highlight new treatment perspectives in children and adolescents, which have already been described in the literature regarding adult patients.

The causes of embryological developmental anomalies leading to laryngotracheoesophageal clefts (LTECs) are not known, but are proposed to be multifactorial, including genetic and environmental factors. Haploinsufficiency of the RERE gene might contribute to different phenotypes seen in individuals with 1p36 deletions. We describe a neonate of an obese mother, diagnosed with type IV LTEC and type III esophageal atresia (EA), in which a 1p36 deletion including the RERE gene was detected. On the second day of life, a right thoracotomy and extrapleural esophagus atresia repair were attempted. One week later, a right cervical approach was performed to separate the cervical esophagus from the trachea. Three months later, a thoracic termino-terminal anastomosis of the esophagus was performed. An anterior fundoplication was required at 8 months of age due to severe gastroesophageal reflux and failure to thrive. A causal role of 1p36 deletions including the RERE gene in the malformation is proposed. Moreover, additional parental factors must be considered. Future studies are mandatory to elucidate genomic and epigenomic susceptibility factors that underlie these congenital malformations. A multiteam approach is a crucial factor in the successful management of affected patients.

To date, relatively few studies have been specifically designed to identify the proteome profile in pulmonary pediatric disease. The aim of this study was to survey proteins present in bronchoalveo...

Aim: Elevated calprotectin levels have been reported in obese adults but have not been evaluated in pediatric population. We investigated the characteristics of serum calprotectin in overweight and obese children and its association with metabolic comorbidities. Methods: We enrolled 131 children (11.7 ± 4.1 years). According to body mass index (BMI), the subjects were divided into 3 groups: obese > 95th percentile; overweight BMI 75th–95th percentile, and normal weight BMI < 75th percentile. Patients were classified as having Metabolic Syndrome if they met 3 or more of the following criteria for age and sex: BMI > 97th percentile, triglycerides > 95th percentile, high-density lipoprotein cholesterol < 5th percentile, systolic and/or diastolic blood pressure > 95th percentile, and impaired glucose tolerance. In all patients, calprotectin serum levels were also detected. Results: Calprotectin was higher in obese and overweight children than normal weight subjects (p < 0.001), with calprotectin in females being significantly higher than in males (p = 0.04). Increased calprotectin was related to pathological fasting blood glucose (p < 0.001) and insulin resistance (p = 0.03), while BMI (p = 0.001), and diastolic pressure (p = 0.001) are independent factors for increased calprotectin. Conclusions: Our findings confirm the association between increased calprotectin and obesity also in children and suggest the potential utility of this biomarker in the monitoring of its metabolic complications.

Renal leiomyoma (RL) is a rare benign tumor originating from muscle cells and has been rarely described in the pediatric age-group. A case of a large RL in an 11-year-old girl is reported with a literature review. The girl was admitted for abdominal pain due to mass effect. Contrast-enhanced CT showed a circumscribed low density mass (22 × 19 × 12 cm) arising from the right kidney. A right nephrectomy was performed. The mass was well defined and encapsulated. Only the histopathology and immunohistochemistry confirmed the diagnosis of RL. Even though partial nephrectomy may be possible, radical nephrectomy remains the recommended treatment for large leiomyoma.

Hirschsprung's disease and, more rarely, intestinal duplication can both cause intestinal obstruction in neonates. The simultaneous occurrence of these two diseases is reported in only two studies, and in both cases, intestinal duplication was an incidental finding, as it had not determined clinical intestinal occlusion. This paper reports a unique case of coexistence of the two conditions, with both causing intestinal obstruction, delayed appropriate, and definitive surgical treatment.

Mesenchymal stromal cells (MSCs) have been proposed as a potential therapy to treat congenital and acquired lung diseases. Due to their tissue-regenerative, anti-fibrotic, and immunomodulatory properties, MSCs combined with other therapy or alone could be considered as a new approach for repair and regeneration of the lung during disease progression and/or after post- surgical injury. Children interstitial lung disease (chILD) represent highly heterogeneous rare respiratory diseases, with a wild range of age of onset and disease expression. The chILD is characterized by inflammatory and fibrotic changes of the pulmonary parenchyma, leading to gas exchange impairment and chronic respiratory failure associated with high morbidity and mortality. The therapeutic strategy is mainly based on the use of corticosteroids, hydroxychloroquine, azithromycin, and supportive care; however, the efficacy is variable, and their long-term use is associated with severe toxicity. The role of MSCs as treatment has been proposed in clinical and pre-clinical studies. In this narrative review, we report on the currently available on MSCs treatment as therapeutical strategy in chILD. The progress into the therapy of respiratory disease in children is mandatory to ameliorate the prognosis and to prevent the progression in adult age. Cell therapy may be a future therapy from both a pediatric and pediatric surgeon’s point of view.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades, the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life and creating new challenges and goals. Many nutritional problems, gastrointestinal disorders and metabolic and endocrine alterations are commonly identified in patients affected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidisciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Introduction The association between congenital pulmonary airway malformations (CPAM) and malignancy is reported in the literature. Interactions between the tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. We characterized MSCs isolated from CPAM lesions in order to define potential malignancy risks. Methods CPAM II pulmonary tissue was used for MSC expansion; a “healthy” lung section from the same child was used as a comparator. Morphology, immunophenotype, differentiation and immunological capacity, proliferative growth, gene signature telomerase activity, and in vivo tumorigenicity in nude mice were evaluated. Results MSCs were successfully isolated and propagated from CPAM tissue. CPAM-MSCs presented the typical MSC morphology and phenotype, while exhibiting high proliferative capacity, reaching confluence at a median time of 5 days as well as differentiation capabilities. CPAM-MSCs at early passages were not neoplastic and chromosomally normal, even though unbalanced chromosomal rearrangements were noted by molecular karyotype. Conclusions CPAM-MSCs exhibited specific features similar to tumor derived MSCs. Whilst there was no evidence of malignant transformation in the cystic tissue, our results provide evidence that this abnormal tissue has malignant potential. MSCs are considered important players in the tumor microenvironment and they have been closely linked to regulation of tumor survival, growth, and progression. Thus, early lesion resection also in asymptomatic patients might be indicated to exclude that the microenvironment may be potentially permissive to cancer development.

Transjugular intrahepatic portosystemic shunt (TIPS) placement is a standard procedure for the treatment of portal hypertension complications. When this conventional approach is not feasible, alternative procedures for systemic diversion of portal blood have been proposed. A one-step interventional approach, combining minilaparotomy-assisted transmesenteric (MAT) antegrade portal recanalization and TIPS, is described in an adolescent with recurrent esophageal varice bleeding and portal cavernoma (PC). A 16-year-old girl was admitted to our Unit because of repeated bleeding episodes over a short period of time due to esophageal varices in the context of a PC. A portal vein recanalization through an ileocolic vein isolation with the MAT approach followed by TIPS during the same session was performed. In the case of failed portal recanalization, this approach, would also be useful for varice endovascular embolization. Postoperative recovery was uneventful. Treatment consisting of propanolol, enoxaparin and a proton pump inhibitor was prescribed after the procedure. One month post-op, contrast enhanced computed tomography confirmed the patency of the portal and intrahepatic stent grafts. No residual peritoneal fluid was detected nor opacification of the large varices. Endoscopy showed good improvement of the varices. Doppler ultrasound confirmed the accelerated flow in the portal stent and hepatopetal flow inside the intrahepatic portal branches. Three months post-op, TIPS maintained its hourglass shape despite a slight expansion. Portal hypertension and life threatening conditions related to PC would benefit from one-step portal recanalization. MAT-TIPS is feasible and safe for the treatment of PC even in children. This minimally invasive procedure avoids or delays surgical treatment or re-transplantation when necessary in pediatric patients.

Animal-assisted interventions are associated with positive effects on human psychological and physiological health. Although quality standards in animal-assisted interventions appear to be high, only few investigations have focused on potential welfare implications in therapy dogs. In the present study, we monitored behavioral measures and heart rate in a therapy dog that participated in animal-assisted therapy during postoperative awakening in a pediatric surgery ward. Work-related activity, behavior, response to human action, and heart rate were analyzed for more than 20 working sessions in an experienced therapy dog. No physiological or behavioral indicators of stress, fatigue, or exhaustion were present during animal-assisted therapy, suggesting that, with the limited generalizability of a case study, this activity did not negatively impact on the welfare of the dog. Further investigation into the effects of animal-assisted therapy on dogs' physiological markers and behavior is warranted.

Introduction: In children with disabilities, precocious puberty (PP) has been reported, however there is a paucity of studies on delayed puberty (DP) in neurologically impaired (NI) children.Patients and Methods: We retrospectively evaluated 65 patients with severe disabilities (6–18 years). DP was considered whenever the following criteria where satisfied, respectively, for girls and boys, absence of breast development by age 13 or menarche by age 15, absence of at least 4 mL testicular growth volume or 2.5 cm length by age 14. PP was defined as the presence of puberty signs at

Introduction: Allostatic load (AL) refers to the physiological response associated with the burden of chronic stress. Excessive weight is an important source of physiological stress that promotes a detrimental chronic low-inflammation state. In order to define a correlation between cumulative biological dysregulation and excess weight, we measured AL scores in a pediatric population.Patients and Methods: We enrolled 164 children and adolescents (11.89 ± 3.89). According to their body mass index (BMI) threshold, subjects were classified as normal in the BMI < 75th percentile, overweight in the BMI 75–95th percentile or obese in the BMI >95th percentile. Data based on 16 biomarkers were used to create the AL score. A dichotomous outcome for high AL was defined in those who had more than four dysregulated components.Results: High AL was noted in 88/164 subjects (53.65%), without significant differences between genders (p = 0.07) or pubertal status (p = 0.10). Subjects with a high AL, in addition to a higher BMI (p < 0.001), showed higher WC and WC/HtR (p < 0.001), triglycerides (p = 0.002), fasting blood glucose (p = 0.03), insulin resistance (p < 0.001), systolic (p < 0.001) and diastolic blood pressure (p = 0.001), GGT (p = 0.01), PCR (p = 0.01), and calprotectin (p < 0.01) as well as lower HDL cholesterol (p = 0.002) than subjects with a low AL. The rate of the cumulative biological dysregulation increased progressively with increases in BMI (p < 0.001).Conclusions: A high AL was associated with excess weight. AL may be considered a significant factor correlated with increased morbidity in children who are overweight/obese.

A limited number of sclerosing Angiomatoid Nodular Transformation (SANT) have been reported in pediatric age. We describe the first case of SANT occurring in a nine-week-old female infant that was admitted to our unit for severe abdominal distension and rectal bleeding. Enlarged spleen was detected on physical examination. Laboratory investigations revealed severe anemia and coagulation abnormalities. Abdominal ultrasound and computed tomography revealed ascites and splenomegaly with a large mass at the lower medial splenic pole. A diagnosis of intraabdominal hemorrhage was presumed and an exploratory laparotomy was performed. A complete transformation of the giant splenomegaly to bossellated masses and multiple bleeding capsular ruptures without subcapsular hematoma were found and an urgent splenectomy was performed. At histology, a SANT was diagnosed (CD34, CD31, CD8 positivity). The postoperative follow up was uneventful. SANT may also occur in infancy with a potentially lifethreatening presentation. Splenectomy may represent the only treatment in severe cases.