Search

Video assisted thoracoscopic surgery (VATS) has been adopted in pediatric age for the treatment of congenital lung malformations (CLM). The success of VATS in pediatrics largely depends on the surgeon's skill ability to understand the airways, vascular system and lung parenchyma anatomy in CLM. In the last years, virtual reality (VR) and 3-dimensional (3D) printing of organ models and VR head mounted display (HMD) technologies have been introduced for completion of preoperative planning in adult patients. To date no reports about the use of VR HMD technologies in a pediatric setting are available. The aim of this report is to introduce a VR HMD model in VATS procedure to improve the quality of care in children with CLM. VR HMD set-up for planning thoracoscopic surgery was performed in a series of pediatric patients with diagnosis of CLM. The preoperative VR HMD evaluation allowed a navigation into the malformation with the aim to explore, interact, and make the surgeon more confident and skilled to answer to the traps. A development of surgical simulations models and teaching program dedicated to education and training in pediatric VATS is suitable among the pediatric surgery community. Further studies should demonstrate all the benefits of such technology in pediatric patients submitted to VATS procedure.

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 explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G 0 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pelizzo, Riva, Croce, Avanzini, Acquafredda, de Silvestri, Mazzon, Bramanti, Zuccotti, Mazzini and Calcaterra.)

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.

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.

Colonic volvulus (CV) is a rare but potentially life-threatening condition with unclear etiopathogenesis. To date, less than 80 pediatric cases have been described. Hirschsprung's disease (HD) is associated with CV in 17% of cases, representing a significant risk factor. Non-HD CV is an even more complex entity. The aim of this study is to describe a series of patients with CV to accentuate some peculiar aspects of this disease. We performed a retrospective study (period: 2012-2021) collecting information of patients with CV. Data analyzed included: demographics, medical history, presenting symptoms and radiological and surgical details. Eleven patients (12.5 ± 2.8 years; 7F/4M) had CV (eight sigmoid, two transverse colon, one total colon). Five patients had associated anomalies and three had HD. A two-step approach with volvulus endoscopic/radiological detorsion followed by intestinal resection was attempted in eight cases (one endoscopic approach failed). Three patients required surgery at admission. At follow-up, two patients developed recurrent intestinal obstruction, one of whom also had anastomotic stenosis. Colonic volvulus is a challenging condition that requires prompt patient care. A missed diagnosis could lead to severe complications. The evaluation of the patient should include a careful histological examination (searching for HD and alpha-actin deficiency), immunologic and metabolic screening, neurological tests and detection of chronic intestinal pseudo-obstruction (CIPO). Lifelong follow-up is mandatory for the early recognition and treatment of progressive diseases involving the proximal gastrointestinal tract.

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., (© 2021. The Author(s).)

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.

Introduction: Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmed trait d'union . We evaluated the relationship between IR and an established ovarian reserve biomarker such as anti-mullerian hormone (AMH) together with other potential modulators of ovarian physiology (adiponectin and kisspeptin) in young reproductive-aged group women with obesity and type 1 diabetes (T1D)., Patients and Methods: We 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., Results: adiponectin and kisspeptin levels were significantly different into groups ( p  ≤ .001), whereas AMH levels were not. Adiponectin values were higher in controls compared to patients with obesity ( p  < .001) and T1D ( p  = .02). Kisspeptin levels were lower in controls compared to patients with obesity ( p  = .001), without reaching statistical significance when compared to T1D ( p  = .06). IR was associated with lower adiponectin and higher kisspeptin levels ( p  < .001 and p  = .02, respectively), but not with AMH., Conclusions: 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.

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5 . Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.

Different mechanisms were proposed as responsible for COVID-19 neurological symptoms but a clear one has not been established yet. In this work we aimed to study SARS-CoV-2 capacity to infect pediatric human cortical neuronal HCN-2 cells, studying the changes in the transcriptomic profile by next generation sequencing. SARS-CoV-2 was able to replicate in HCN-2 cells, that did not express ACE2 , confirmed also with Western blot, and TMPRSS2 . Looking for pattern recognition receptor expression, we found the deregulation of scavenger receptors, such as SR-B1, and the downregulation of genes encoding for Nod-like receptors. On the other hand, TLR1 , TLR4 and TLR6 encoding for Toll-like receptors (TLRs) were upregulated. We also found the upregulation of genes encoding for ERK, JNK, NF-κB and Caspase 8 in our transcriptomic analysis. Regarding the expression of known receptors for viral RNA, only RIG-1 showed an increased expression; downstream RIG-1, the genes encoding for TRAF3, IKKε and IRF3 were downregulated. We also found the upregulation of genes encoding for chemokines and accordingly we found an increase in cytokine/chemokine levels in the medium. According to our results, it is possible to speculate that additionally to ACE2 and TMPRSS2, also other receptors may interact with SARS-CoV-2 proteins and mediate its entry or pathogenesis in pediatric cortical neurons infected with SARS-CoV-2. In particular, TLRs signaling could be crucial for the neurological involvement related to SARS-CoV-2 infection.

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, 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.

Background: The initial wave of the Covid-19 pandemic has hit Italy, and Lombardy in particular, with violence, forcing to reshape all hospitals' activities; this happened even in pediatric hospitals, although the young population seemed initially spared from the disease. "Vittore Buzzi" Children's Hospital, which is a pediatric/maternal hospital located in Milan (Lombardy Region), had to stop elective procedures-with the exception of urgent/emergent ones-between February and May 2020 to leave space and resources to adults' care. We describe the challenges of reshaping the hospital's identity and structure, and restarting pediatric surgery and anesthesia, from May on, in the most hit area of the world, with the purpose to avoid and contain infections. Both patients and caregivers admitted to hospital have been tested for Sars-CoV-2 in every case., Methods: Observational cohort study via review of clinical charts of patients undergoing surgery between 16th May and 30th September 2020, together with SARS-CoV -2 RT-PCR testing outcomes, and comparison to same period surgeries in 2019., Results: An increase of approximately 70% in pediatric surgeries (OR 1.68 [1.33-2.13], P < .001) and a higher increase in the number of surgeries were reported (OR 1.75 (1.43-2.15), P < .001). Considering only urgent procedures, a significant difference in the distribution of the type of surgery was observed (Chi-squared P-value < .001). Sars-CoV-2-positive patients have been 0.8% of total number; 14% of these was discovered through caregiver's positivity., Conclusion: We describe our pathway for safe pediatric surgery and anesthesia and the importance of testing both patient and caregiver., (© 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Frailty (FI) and metabolic syndrome (MS) are each associated with adverse health outcomes. A relationship between FI and MS has previously been described in adults. We considered the prevalence of a metabolically unhealthy phenotype (MUP) in malnourished children with neurological impairment and in subjects with obesity in comparison to a group of elderly individuals at risk of FI, and we did so in order to define the potential similarities that may underline the risk of FI in specific children. We considered 50 undernourished (defined as having a body mass index of BMI ≤ 2, standard deviation score, SDS, according to World Health Organization) disabled children; 50 children with obesity (BMI ≥ 2 SDS); 50 children who were a normal weight (-1 SDS ≤ BMI ≤ +1 SDS); 21 patients who were >75 years old. MUP was defined as the presence of at least one of the following risk factors: hypertension, hyperglycemia or diabetes, hypercholesterolemia, and hypertriglyceridemia. In children with a disability and obesity, a higher prevalence ( p < 0.001) and risk (disability OR 54.88, obesity OR 13.37) of MUP was noted compared to children of a normal weight. Compared to elderly patients, the prevalence of MUP did not differ in disabled children. On the contrary, MUP was lower in children with obesity ( p < 0.001) and in pediatric subjects of a normal weight ( p < 0.01). MS might play a key role in "pediatric" frailty. The extremities of the aging process and malnutrition are likely key factors in the development of FI. A multidisciplinary approach to FI may represent an important milestone for pediatric care.

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.

An interaction between metabolic glucose impairment and coronavirus disease 2019 is reported. The development of a severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection has been described. We evaluated the impact of MIS-C on glycemic patterns in pediatric patients. A group of 30 children and adolescents affected by MIS-C were considered; all patients were normal weight. Clinical and biochemical assessments, including surrogate markers of insulin resistance (IR) such as homeostasis model analysis-IR (HOMA-IR) and triglyceride-glucose (TyG) indexes, were recorded. Patients were also invited to undergo an intermittently scanned continuous glucose monitoring (isCGM). HOMA-IR index was calculated in 18 patients (60%), of which 17 (94%) revealed a pathological value. TyG index was computed for all patients and pathological values were detected in all cases. In 15 patients, isCGM data were recorded on average for 9 days (±3 days). Overall, average glucose was 105 mg/dL (±16 mg/dL) and average time spent in the 70-180 mg/dL range (TIR) was 93.76%, with nearly 10% of glucose readings in the 141-180 mg/dL range; glycemic fluctuations over the hyperglycemic threshold were detected in four patients. Regular glucose monitoring may be useful to prevent metabolic imbalance and obtain a better outcome.

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, >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 >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.

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.

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 ± 5.6 months. The procedure was uneventful and well-tolerated in all seven cases. At 6.6 ± 2.0 months after TGJ placement, significant weight gain (weight z-score -2.68 ± 0.8 vs -0.9 ± 0.2, p < 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 ± 0.75 vs. 1.6 ± 0.52, p < 0.01). A significant amelioration of QoL after TGJ placement was also recorded; in particular, the biggest improvements were related to parents' perceptions of the general health and emotional state of their babies ( p < 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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 La Pergola, Sgrò, Rebosio, Vavassori, Fava, Codrich, Montanaro, Leva, Schleef, Cheli, Pelizzo, Gamba, Alberti and Betalli.)

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 (>4 years) were included, and anthropometric measurements, nutritional assessment, and energy metabolism were considered. The subjects were defined as undernourished if they met BMI < -2 standard deviation (SD). To grade undernutrition, we defined the prevalence of underweight, stunting, and wasting (cut-off level of <-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 < 0.01). Wasting was noted in 28.6% of patients, of these 5 children were undernourished ( p < 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 < 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 < 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.

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.

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 (<2 cm) was detected in 28.6%. Postoperative EGJ pressures were higher compared to preoperative sphincteric pressures ( p < 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.

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.

Introduction: This is the report of the first official survey from the Italian Society of Pediatric Surgery (ISPS) to appraise the distribution and organization of bedside surgery in the neonatal intensive care units (NICU) in Italy., Methods: A questionnaire requesting general data, staff data and workload data of the centers was developed and sent by means of an online cloud-based software instrument to all Italian pediatric surgery Units., Results: The survey was answered by 34 (65%) out of 52 centers. NICU bedside surgery is reported in 81.8% of the pediatric surgery centers. A lower prevalence of bedside surgical practice in the NICU was reported for Southern Italy and the islands than for Northern Italy and Central Italy (Southern

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., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (©Copyright: the Author(s).)

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., (Copyright © 2020 Destro, Selvaggio, Lima, Riccipetitoni, Klersy, Di Salvo, Marinoni, Calcaterra and Pelizzo.)

Background The coexistence of celiac disease (CD) and obesity/overweight is not unusual. Objective 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.

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 < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48-67) and 85% (95%CI 74-92), respectively, with a PPV = 86% (95%CI 76-93) and PPN = 54% (95%CI 43-54); the area under the ROC curve was 0.71 (95%CI 0.65-0.78). 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.

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., Competing Interests: The authors declare no conflict of interest.

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., (Copyright © 2020 Pelizzo, Bussani, De Silvestri, Di Mitri, Rosone, Amoroso, Milazzo, Girgenti, Mura, Unti, Rozze, Shafiei and Calcaterra.)

Background We depicted gender-differences in metabolic syndrome (MS) clustering before and after puberty in pediatrics, in order to develop gender specific preventive strategies for childhood obesity. Methods We considered 1079 children and adolescents (529 females and 550 males; mean age 11.5 ± 2.8 year). According to body mass index (BMI) percentiles the subjects were classified as normal weight BMI <75th, overweight BMI 75-95th and with obesity BMI >95th. MS was diagnosed when three of the following criteria for age and sex percentiles were met: BMI >95th, triglycerides (TGs) level >95th, high-density lipoprotein-cholesterol (HDL-c) level <5th, blood pressure (blood pressure) >95th percentile, fasting blood glucose (FBG) >100 mg/dL and/or homeostatic model assessment- insulin resistance (HOMA-IR) >97.5th percentile. Results The prevalence of dismetabolic factors was similar in both genders, except for pathological BP, which was higher in males (p = 0.02). MS was detected only in patients with obesity, with a higher prevalence in pubertal than late/post-pubertal subjects (p < 0.001), without any significant difference between gender. In pre-puberty, the most common MS combination was obesity (HBMI) + hypertension (HBP) + hyperglycemia/insulin resistance (HGLY/IR) followed by HBMI + low HDL-levels (LHDL) + HGLY/IR versus HBMI + HBP + HGLY/IR followed by HBMI + HBP + LHDL, respectively, in females and males. In the early and late/post-pubertal periods, the most prevalent combination remained similar to pre-puberty, additionally in both sexes other combinations, such as HBMI + HTG + HBP + HGLY/IR, HBMI +  HBP + LHDL + HGLY/IR, HBMI + HTG + LHDL + HGLY/IR and HBMI + HTG + LHDL + HBP + HGLY/IR were also detected, differently distributed in males and females. Conclusions We confirm that MS is an important consequence related to obesity, particularly in the post-puberty stage. Some gender-based differences should be considered early in order to identify specific preventive and treatment strategies.

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., (© 2020 S. Karger AG, Basel.)

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&#95;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., (© 2019 Wiley Periodicals, Inc.)

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., Competing Interests: Conflict of interest: The authors declare no potential conflict of interests., (©Copyright: the Author(s), 2019.)

Dehydration is common and frequently under-diagnosed in chronic malnourished children, leading to life-threatening conditions. In this pilot study we applied bioimpedance vector analysis (BIVA) to determine hydration status in 52 neurologically impaired (NI) paediatric patients (14.08 ± 5.32). Clinical and biochemical data were used to define malnutrition and dehydration. Body composition analysis and hydration were also assessed by BIVA and we considered 143 normal-weight healthy subjects (15.0 ± 1.7), as controls for hydration status assessment. BIVA revealed a pathological hydration status in NI children, showing higher resistance (p < 0.001) and reactance values (p = 0.001) compared to controls. No differences in reactance and resistance were detected between well-nourished and under-nourished subjects. Four patients out of 52 showed mild signs of dehydration; no severe dehydration was detected. Laboratory data, suggestive for dehydration, were similar in well-nourished and under-nourished NI subjects. In conclusion, in our sample of NI paediatrics, dehydration according to clinical signs and laboratory data was under-diagnosed. BIVA showed specific bioelectrical characteristics that could be compatible with impaired hydration status. Further studies are necessary to confirm that BIVA may an applicable tool for defining dehydration status and guiding rehydration in NI children.

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 <8 and 9 years of age, respectively, for girls and boys. In all patients, a physical examination was performed and a family history of DP was obtained. A hormonal panel was evaluated when puberty disorders were detected. As a control group we evaluated 50 age-matched healthy subjects. Results: Puberty disorders were observed in 12 NI patients and in one control (18.5 vs. 2%, p < 0.01). DP was detected in 8 NI subjects (3M/5F) and in one healthy boy ( p = 0.04), without differences between genders among patients from the NI group ( p = 0.2), and compared with the controls ( p = 0.4). In five of the eight NI subjects, Tanner stage 1 was observed; in three subjects adrenarche was present without pubertal progression for more than 2 years. Low levels of gonadotropins were detected in all NI subjects with DP. The number of subjects with a BMI <-3SDS was higher in NI patients with DP compared to NI subjects with normal puberty ( p < 0.01); normal weight was detected in one healthy boy. The family history for pubertal delay was negative in all NI patients with DP and positive in the control subject. Conclusion: NI children and adolescents may experience delayed pubertal changes. An endocrinological follow-up with pubertal development monitoring is strongly recommended in order to evaluate whether targeted interventions may improve outcomes., (Copyright © 2019 Calcaterra, Cena, De Silvestri, Di Mitri and Pelizzo.)

Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Insulin resistance (IR) plays a key role in the pathogenesis of type 2 diabetes (T2D). In neurologically impaired (NI) children unfavorable cardio-metabolic risk profile with high prevalence of IR has been reported. We evaluated the prevalence of T2D in NI children and adolescents, in order to define if a dedicated glucose monitoring may be recommended in these subjects. Methods: We retrospectively evaluated 63 patients (11.4 ± 4.0 years) with severe disabilities. Auxological parameters were recorded. Metabolic blood assays included fasting blood glucose (FBG), fasting insulin, triglycerides (TG). IR was detected with the homeostasis model assessment for insulin resistance (HOMA-IR > 97.5th percentile for age and sex) and triglyceride-glucose index (TyG index > 7.88). Elevated FBG was defined with values >100 mg/dl. T2D was defined according to American Diabetes Association criteria. Results: Impaired insulin sensitivity, pathological TyG index and elevated FBG were observed, respectively, in 41.3, 63.5, and 11.1% patients. T2D was diagnosed in 3.2% asymptomatic patients. The prevalence of diabetes was higher in pre-pubertal compared to pubertal subjects ( p = 0.03). Conclusions: T2D in NI children and adolescents without obesity could represent a new emerging entity. IR and/or surrogate markers of IR index may be useful for the primary screening of this at-risk disabled population so as to prevent diabetes.

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.

Objective: The triglyceride and glucose (TyG) index has been proposed as a simple surrogate of insulin resistance (IR) with high sensitivity as an IR index besides the well known homeostasis model assessment of IR (HOMA-IR). Limited data are reported in children. We investigated the sensitivity and specificity of TyG index in a pediatric Caucasian population, as a surrogate measure of IR and compared the results with HOMA-IR., Methods: We enrolled 541 children (11.7±2.71 yrs). According to body mass index (BMI) chart, the subjects were divided into three groups: normal weight BMI<75th percentile, overweight BMI 75th–95th percentile, and obese>95th percentile. TyG index was calculated as (ln[fasting triglycerides(mg/dl)×fasting plasma glucose(mg/dl)/2]) and considered pathological when exceeding 7.88. HOMA-IR was calculated as (insulin×glucose)/22.5 and defined pathological whenever exceeding 97.5th percentile for age and sex., Results: In children with overweight/obesity TyG index was higher compared to normal weight subjects (p<0.001). TyG index was correlated with BMI (p<0.001); WHtR (p<0.001), total and HDL cholesterol (p<0.001); ALT (p<0.001), blood pressure (p<0.001). A correlation between TyG index and HOMAIR (p<0.001) as well as high TyG index and pathological HOMA-IR (p<0.001) were noted. The optimal cut-off for IR was considered 7.98 (sensitivity 60%; specificity 78%; AUC 0.69)., Conclusions: TyG index is a useful and cost-effective index of IR among children and adolescents. The cutoff 7.98 may be used for IR risk screening in childhood obesity, but we recommend caution when used in other populations.