Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

Dental anomalies as a possible clue of 1p36 deletion syndrome due to germline mosaicism: a case report.

BACKGROUND: Monosomy 1p36 is the most common terminal deletion syndrome with an autosomal dominant pattern of inheritance. This syndrome is defined by an extremely wide spectrum of characteristics; however, developmental delay and intellectual disability of various degree are present in all patients and about the 90% of patients have a severe intellectual disability. Dental agenesis or other dental anomalies have not been described in previous reports. CASE PRESENTATION: We report the case of two little sisters born from healthy and non-consanguineous parents, presenting with dental anomalies and one of them with epilepsy, dilated cardiomyopathy with left-ventricular non-compaction, strabismus, history of poor growth, hypotonia and mild language delay. Patients were evaluated in several departments (genetic, child neuropsychiatric, cardiology, odontostomatology, ophthalmology, otorhinolaryngology) of Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy. They underwent investigations such as electrocardiogram, echocardiogram, dental orthopantomography X-Ray and Computed Tomography, electroencephalograms, abdomen ultrasound, blood tests, IQ tests, genetic analysis. They both have an Intelligence Quotient greater than 70 and a negative neurologic exam. Each sister carries the same 1p36 deletion of about 2.3 Mb. Genetic analysis of the parents' blood samples (Single Nucleotide Polymorphism- array, karyotype and Fluorescent In Situ Hybridization) did not reveal any deletion, translocation or inversion and confirmed the paternity. A third sib of the probands does not carry the 1p36 deletion or other quantitative alterations. CONCLUSION: This report describes a new trait linked to monosomy 1p36, namely a mild intellectual outcome associated with significant dental anomalies. Our finding suggests that 1p36 deletion syndrome may present with a mild cognitive impairment or even with a normal intellectual development: this is very important for the genetic counselling, especially in a prenatal setting. Moreover, we report the third study with recurrent 1p36 deletion syndrome in two siblings, likely due to germline mosaicism. Finally, we believe that the dental anomalies should be investigated in 1p36 deletion syndrome and that the spectrum of the condition could be broader than we assume.

An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Off-Label Use of Sirolimus and Everolimus in a Pediatric Center: A Case Series and Review of the Literature.

BACKGROUND: It has been 15 years since sirolimus, an mTOR inhibitor, received Food and Drug Administration approval to prevent acute rejection in kidney transplantation, and 8 years since its analog everolimus acquired the same status. Since then, these drugs have become more and more utilized and their immunosuppressive and antiproliferative properties have been tested in a great variety of clinical conditions, often achieving excellent results. Despite such positive evidence, the on-label indications for these rapalogs are still very restrictive, especially in children. AIMS: The aims of this study were to describe our center's experience with sirolimus and everolimus in managing rare pediatric conditions for which mTOR inhibitors have been reported as a therapeutic option, although without conclusive approval from regulatory agencies, and to evaluate safety and tolerability of the treatment at the prescribed doses. METHODS: All the subjects who received off-label sirolimus or everolimus at the Pediatric Department of the IRCCS Burlo Garofolo in the last 13 years were included. For each disease found in our case series, we reviewed the current scientific literature. RESULTS: Off-label treatment with rapalogs was prescribed in 16 children (11 males, 5 females, median age of 9.5 years, range 1-16 years). Seven had immunologic disorders: four autoimmune lymphoproliferative syndrome (ALPS), one multicentric Castleman disease (mCD), one activated PI3K delta kinase syndrome (APDS), and one immunodysregulation with polyendocrinopathy enteropathy X-linked (IPEX). Eight had proliferative disorders or vascular anomalies: one cystic lymphangioma, two Bannayan-Riley-Ruvalcaba syndrome (BRRS), one blue rubber bleb nevus syndrome (BRBNS), two tuberous sclerosis complex (TSC), and one low-flow mixed arterial and venous malformation. One case had congenital hyperinsulinism (CHI). The average dosage administered was 1 mg/m2 for sirolimus and 7 mg/m2 for everolimus. We experienced a good measurable clinical improvement in 14 patients. Nobody experienced serious adverse events (SAEs). The therapy was interrupted in two cases, for lack of efficacy and poor tolerance in one case and for occurrence of bacterial pneumonia in the other one. A review of the literature identified 101 published reports that met our inclusion criteria. CONCLUSIONS: Although use of mTOR inhibitors has been considered to be complicated, our experience shows that, using low dosages, it is possible to obtain relevant clinical improvements, with a good profile of safety and tolerability.

Validation of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative Version.

BACKGROUND: This study evaluated the validity and reliability of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative version (I-NCCPC-PV). METHODS: The original NCCPC-PV version was translated into Italian following the guidelines for "the translation, adaptation, and validation of instruments or scales for cross-cultural healthcare research". We tested the Italian NCCPC-PV version (I-NCCPC-PV) in 40 children (3-18 years of age) with severe to profound Intellectual Disability and no verbal communication. Each child's behavior was observed by a parent or caregiver and by an external observer in a quiet situation and a painful one. They independently assessed the child's level of pain using the translated Italian version of the NCCPCPV (I-NCCPC-PV). RESULTS: The results from 80 assessments showed that children's behavioral signs differed significantly between painful and calm situations (p < 0.001). The inter-rater reliability was poor in a quiet condition (ICC 0.62) and fair in a painful situation (ICC 0.77). The inter-rater agreement was good in both calm and painful conditions (72.50% and 77.50% respectively). CONCLUSION: The Italian version of the NCCPC-PV (I-NCCPC-PV) can be used for pain assessment in children with Intellectual Disability who lack verbal communication.

Comparison of two European paediatric emergency departments: does primary care organisation influence emergency attendance?

BACKROUND: To compare paediatric Emergency Department (ED) attendances and admission outcomes in two European hospitals with different paediatric primary care set-up. METHODS: This is a retrospective prevalence study comparing all paediatric ED attendances during calendar years 2013 in two EDs with similar catchment area: one in Italy (Trieste) where paediatric primary care is provided by office paediatricians, the other, in the UK (Cambridge), where paediatric primary care is provided by general practitioners. Data on reason for presentation, discharge diagnosis and admission rate were collected and sub-group analysis for specific age groups (<1 year, 1-4 years, 5-15 years) was performed. RESULTS: Over 12 months, 20.331 children (0-15 years old) were seen in Cambridge and 18.646 in Trieste, with a very similar age distribution in both centres, except for the youngest age group: the percentage of infants seen in comparison with the total number of children attending ED was 1/3 higher in England than in Italy (15.4% vs 11.4%). The reasons for attendance were similar: under 1 year of age, the chief complaints were fever, breathing difficulties and gastrointestinal problems while in the older age groups trauma represented the commonest reason. Among discharge diagnoses, no differences were found between the two hospitals, except for faltering growth and "well child", more frequently diagnosed in English children under 5 years. The proportion of admissions was three times higher in Cambridge (14.1% vs 4.8%) with most children being admitted for infectious diseases. CONCLUSIONS: ED attendances in infants are more common in a primary care setting provided by general practicioner and, moreover, admission rates in all age groups are 1/3 reduced by primary care based paediatricians. Due to the methodological limits of this study, it isn't possible to evaluate whether these results depend only on paediatric primary care set-up or be determined by other confounding factors. New studies are needed to confirm this preliminary evidence.

Paediatricians' attitudes toward pain in children with severe cognitive impairment. A regional survey.

INTRODUCTION: pain is a frequent and relevant problem in children with severe cognitive impairments. Assessing pain in these patients can be difficult. Specific observational tools such as the Collignon Giusiano Questionnaire or the Non-communicating Children's Pain Checklist ( NCCPC) are available, but their use is not widespread. Children with severe cognitive impairment are frequently in need of painful procedures but data about availability of procedural sedation in this setting are limited. OBJECTIVE OF THE STUDY: to evaluate paediatricians' attitudes toward pain in children with severe cognitive impairment by measuring the use of specific pain scales and the use of analgesia or procedural sedation in course of a frequent procedure such as botulinum toxin injection. METHODS: phone interview with the doctor on duty of 56 paediatric wards in 3 regions of the North East of Italy, addressing the routine use of pain scales, and the use of specific observational tools for non communicating children. A phone interview was also conducted in 4 centers routinely practicing botulinum toxin injection about the use of analgesia or procedural sedation. RESULTS: 1 centre out of 55 reported to use specific scales for children with cognitive impairment, specifically the Collignon Giusiano Questionnaire. No centre used procedural sedation for botulinum toxin injection. CONCLUSION: in the investigated area there is a lack of attention to pain in children with severe cognitive impairment. Specific educational efforts should be done to improve the quality of care in this setting.

Does EMLA cream application interfere with the success of venipuncture or venous cannulation? A prospective multicenter observational study.

UNLABELLED: Venipuncture and intravenous cannulation are the most common painful procedures performed on children. The most widely used topical anesthetic is eutectic mixture of local anesthetics (EMLA). EMLA use is associated with a transient cutaneous vasoconstriction which can make it difficult to identify veins. We assessed with a prospective, multicenter, observational study whether EMLA interferes with venipuncture and intravenous cannulation. The primary study outcome was a success at first attempt in the course of venipuncture or venous cannulation. The study enrolled 388 children; 255 of them received EMLA and 133 did not. Eighty-six percent of procedures were successful at the first attempt in the EMLA group and 76.7 % in the no EMLA group. CONCLUSION: In this study, EMLA use did not interfere with the success of venipuncture or venous cannulation in children.

Pain in cognitively impaired children: a focus for general pediatricians.

UNLABELLED: Pain in children with cognitive impairment and cerebral palsy is a particularly relevant issue due to its high prevalence and impact on quality of life. We review available evidence about prevalence of pain, causes and specific treatment, recognition and use of specific pain scales, physiology, and consequences of pain in this subset of patients. CONCLUSIONS: Pain is very common and is a critical determinant of quality of life in children with cognitive impairment and cerebral palsy. The diseases and associated complications that frequently expose these patients to pain can be treated and pain prevented. For patients with communication difficulties, appropriate, effective, validated tools are available and should be used to diagnose pain in itself, to >choose analgesic treatment and to determine effectiveness of these therapies. The level of awareness of pediatricians towards this issue seems to be quite low.

Diagnosed child, treated child: food challenge as the first step toward tolerance induction in cow's milk protein allergy.

BACKGROUND: Food challenge is required to assess tolerance in cow milk (CM) allergy. A positive challenge contraindicates the reintroduction of CM. Specific oral tolerance induction (SOTI) is a promising treatment. METHODS: All children admitted for a challenge were prospectively enrolled. To those tolerating between 2 and 150 ml a SOTI protocol was offered. Outcome, adverse reactions, parents' satisfaction were recorded. RESULTS: Out of 245 challenged patients, 175 reacted 122 out of 125, able to tolerate a minimum dose of 2 ml, underwent SOTI. After one year 75.4% were in an unrestricted diet, 16.1% tolerated between 5 and 150 ml, 8.5% stopped SOTI. Side effects were mild, parents' satisfaction was very high. CONCLUSIONS: The majority of children tolerating limited amounts of CM at the challenge acquires tolerance with SOTI without relevant side effects. Maintaining on an exclusion diet partially tolerant children should be considered debatable.

Videogame playing as distraction technique in course of venipuncture.

BACKGROUND: Needle-related procedures (venipuncture, intravenous cannulation) are the most common source of pain and distress for children. Reducing needle related pain and anxiety could be important in order to prevent further distress, especially for children needing multiple hospital admissions. The aim of the present open randomized controlled trial was to investigate the efficacy of adding an active distraction strategy (videogame) to EMLA premedication in needle-related pain in children. METHODS: One-hundred and nine children (4 -10 years of age) were prospectively recruited to enter in the study. Ninety-seven were randomized in two groups: CC group (conventional care: EMLA only) as control group and AD group (active distraction: EMLA plus videogame) as intervention group. Outcome measures were: self-reported pain by mean of FPS-R scale (main study outcome), observer-reported pain by FLACC scale, number of attempts for successful procedure. RESULTS: In both groups FPS-R median rate was 0 (interquartile range: 0-2), with significant pain (FPS-R > 4) reported by 9% of subjects. FLACC median rate was 1 in both groups (interquartile range 0-3 in CC group; 0-2 in AD group). The percentage of children with major pain (FLACC > 4) was 18% in CC group and 9% in AD group (p = 0.2). The median of necessary attempts to succeed in the procedures was 1 (interquartile range 1-2) in both groups.. CONCLUSION: Active distraction doesn't improve EMLA analgesia for iv cannulation and venipuncture. Even though, it resulted in an easily applicable strategy appreciated by children. This technique could be usefully investigated in other painful procedures.

Adverse effects during specific oral tolerance induction: in-hospital "rush" phase.

BACKGROUND: Specific oral tolerance induction (SOTI) is a promising approach in the treatment of severe food allergies. Different protocols have demonstrated its efficacy. Nevertheless, SOTI is still considered an experimental method and should be limited to highly controlled settings. AIMS: To define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of nebulized epinephrine as a first-line treatment of respiratory reactions during in-hospital SOTI for cow's milk allergy. MATERIALS AND METHODS: A retrospective study was conducted by reviewing the medical records of patients admitted for SOTI beginning in 2001. Reactions were classified as mild, moderate and severe on a partially modified Clark scale. Adverse reactions were treated following the International Guidelines with the introduction of nebulized epinephrine for level four reactions. RESULTS: Of 209 patients, 17 were excluded due to the absence of objective reactions. The remaining 192 were classified as follows: Mild Reactions (Clark Scale 1 to 3): 100 patients received either no treatment, oral antihistamines or nebulized steroids; Moderate Reactions (Clark Scale 4): 87 patients treated with nebulized epinephrine and, depending on their symptoms, oral antihistamines, corticosteroids (nebulized, oral or IV) or nebulized beta 2 agonists; Severe Reactions (Clark Scale 5): 5 children, 4 of whom initially underwent one nebulization of epinephrine and eventually required an IM dose. The fifth patient was immediately treated with IM epinephrine due to hypotension. DISCUSSION: adverse reactions during this in-hospital SOTI protocol were frequent but easily manageable. Nebulized epinephrine can play a relevant role in the treatment of respiratory reactions.

Adverse effects during specific oral tolerance induction: in home phase.

BACKGROUND: Specific oral tolerance induction (SOTI) is a promising approach for severe food allergies. There are little data in the literature regarding the home-phase of SOTI, not only with regard to type and frequency of adverse reactions but also regarding the most suitable treatment and protocol. AIMS: To define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of the home-phase of an original SOTI protocol in a large group of children with severe cow's milk (CM) allergy, after the hospital "rush" phase. METHODS: The study was conducted by recording in-home phase adverse events, success and failure as reported by parents, and calling families. Adverse reactions were treated following the International Guidelines, arbitrarily modified by introducing nebulised epinephrine for respiratory reactions, oral beclomethasone for acute gastric pain and oral cromolyn for recurrent gastric pain. RESULTS: Out of 140 patients, 132 were contacted; eight were inaccessible (follow-up 2-84 months). The number of adverse reactions was 1 in every 100 doses. The reactions were treated with nebulised epinephrine (221 reactions), IM epinephrine (6 reactions), and other drugs. Patients with high specific IgE levels (greater than 100 kU(A)/L) and lower CM dose (less than 5 ml) at the end of in-hospital phase showed a higher risk both for number of reactions and use of nebulised epinephrine. CONCLUSIONS: The home phase of SOTI was characterised by a significant number of adverse reactions, mostly managed with an acceptable rate of side effects. Nebulised epinephrine played a pivotal role in respiratory reactions.

Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy in Calabria: clinical, immunological and genetic patterns.

UNLABELLED: Autoimmune polyendocrinopathy-candidiasis-ectodermal- dystrophy (APECED), also known as autoimmune polyendocrine syndrome type 1 (APS-1), is a very rare disease. Diagnosis requires the presence of at least two of three major clinical features: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. DESIGN: In this study, we analyzed Autoimmune Regulator (AIRE) gene mutations and genotype-phenotype correlation in APECED patients originating from Calabria, a region in the south of Italy. PATIENTS AND METHODS: Four patients and their first-degree relatives were evaluated for clinical manifestations, autoantibody presence and AIRE gene mutations. RESULTS: Three patients carried a homozygous W78R mutation on exon 2, typical of patients with APECED from Apulia; the fourth patient had a homozygous R203X mutation on exon 5, typical of APECED patients from Sicily. Clinical disease expression showed wide variability. Analysis of relatives allowed the identification of 6 heterozygotes, none of whom showed major findings of APECED. CONCLUSIONS: No AIRE gene mutations specific to Calabria were found in patients with APS-1, but mutations similar to those in patients from Apulia and Sicily. Heterozygosity for AIRE gene mutation is not associated with major findings of APECED.

Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer.

BACKGROUND: : Radiofrequency ablation (RFA) may be a valuable treatment option for locally advanced pancreatic cancer. The present study examined its feasibility and safety. METHODS: : Fifty patients with locally advanced pancreatic cancer were studied prospectively. Ultrasound-guided RFA was performed during laparotomy. The main outcome measures were short-term morbidity and mortality. RESULTS: : The tumour was located in the pancreatic head or uncinate process in 34 patients and in the body or tail in 16; median diameter was 40 (interquartile range 30-50) mm. RFA was the only treatment in 19 patients. RFA was combined with biliary and gastric bypass in 19 patients, gastric bypass alone in eight, biliary bypass alone in three and pancreaticojejunostomy in one. The 30-day mortality rate was 2 per cent. Abdominal complications occurred in 24 per cent of patients; in half they were directly associated with RFA and treated conservatively. Three patients with surgery-related complications needed reoperation. Reduction of RFA temperature from 105 degrees C to 90 degrees C resulted in a significant reduction in complications (ten versus two of 25 patients; P = 0.028). Median postoperative hospital stay was 10 (range 7-31) days. CONCLUSION: : RFA of locally advanced pancreatic cancer is feasible and relatively well tolerated, with a 24 per cent complication rate.

Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy.

We report a 12-year-old patient with growth retardation, exercise intolerance, lactic acidosis (increasing after exercise) and autoimmune polyendocrinopathy type 2. Muscle biopsy shows abundant COX-negative fibers, subsarcolemmal mitochondrial aggregates and markedly reduced activities of all respiratory chain complexes. Genetic analysis identified two new cosegregating mutations in Met-tRNA (m.4415A>G) and Cox III (m.9922A>C), located in highly conserved regions of MtDNA. Both the mutations are heteroplasmics in multiple patients' tissues. Single-muscle fiber analysis showed significantly higher levels of both the mutations in COX-negative than in normal fibers. In addition, a possible link between the mitochondrial dysfunction and the autoimmune disease is suggested.

Two novel POLG mutations causing hepatic mitochondrial DNA depletion with recurrent hypoketotic hypoglycaemia and fatal liver dysfunction.

BACKGROUND: Inherited mtDNA depletion syndromes (MDS) are a group of severe mitochondrial disorders resulting from defects in nucleus-encoded factors and often associated with severe or fatal liver failure. PATIENT: In this article, we describe the case of an 18-month-old patient with recurrent hypoketotic hypoglycaemia and fatal hepatic dysfunction with liver mtDNA depletion. METHODS: The assessment of mtDNA copy number was performed on leucocytes, liver and muscle biopsy by Quantitative Real Time PCR and total RNA from liver biopsy was used as a template to amplify the cDNA of the POLG1 gene. RESULTS: Sequence analysis identified two previously undescribed mutations (1868T>G and 2263A>G) located in the gene coding the catalytic subunit of mitochondrial DNA polymerase gamma (POLG), predicting an L623W and K755E amino acid change, respectively. Both mutations were located in the highly conserved linker region of the protein and were absent in more than 200 healthy unrelated control subjects. The identification of these two mutations allowed us to perform genetic counselling and prenatal diagnosis. CONCLUSION: Our data further expand the spectrum of POLG1 gene mutations and the unique phenotype reported (late onset isolated liver disease without lactic acidosis) increase the variability of clinical presentations associated with mutations in this gene.