Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy.

The Transition of Care for Patients with Anorectal Malformations and Hirschsprung Disease: A European Survey.

This study aimed at evaluating how transition of care is currently being organized in the European Reference Networks (ERNs) health care providers (HCPs) in pediatric areas and in the Anorectal Malformation Network (ARM-Net) Consortium hospitals. An online questionnaire was sent to a total of 80 surgeons, members of or affiliated members of three networks: ARM-Net Consortium, ERN eUROGEN, and ERN ERNICA. Complete information were obtained for 45 HCPs, most of which deal with transition and still see a few adult patients (ca. 10%). Gynecological, gastroenterological, urological, colorectal, and continence issues were the major problems described by adult patients to their physicians, and in line with these prevalent complaints, they are referred to the appropriate adult specialists. Forty percent of patients complain about sexual and fertility problems, but the percentage of andrologists and sexologists involved in the caring of adult patients with ARM/Hirschsprung's disease is low, just above 10.9%. Most hospitals deal with transition, but three basic criteria (i.e., presence of: [1] an official written transitional program, [2] a transitional coordinator, and [3] written information on transition to be handled to patients) are jointly met only by six HCPs. According to the responders, the most important issue requiring improvement is the lack of interest and of specific preparation by adult specialists. The overall results of this exploratory survey confirm the need for the development of comprehensive programs for transition in these rare and complex diseases, and identify the hospitals that, in collaboration with the networks, could share best practices in organizing structured transitional pathways and well follow-ups.

GAVeCeLT-WoCoVA Consensus on subcutaneously anchored securement devices for the securement of venous catheters: Current evidence and recommendations for future research.

BACKGROUND: Subcutaneously anchored securement devices (or subcutaneous engineered securement devices) have been introduced recently into the clinical practice, but the number of published studies is still scarce. The Italian Group of Long-Term Central Venous Access Devices (GAVeCeLT)-in collaboration with WoCoVA (World Congress on Vascular Access)-has developed a Consensus about the effectiveness, safety, and cost-effectiveness of such devices. METHODS: After the definition of a panel of experts, a systematic collection and review of the literature on subcutaneously anchored securement devices was performed. The panel has been divided in two working groups, one focusing on adult patients and the other on children and neonates. RESULTS: Although the quality of evidence is generally poor, since it is based mainly on non-controlled prospective studies, the panel has concluded that subcutaneously anchored securement devices are overall effective in reducing the risk of dislodgment and they appear to be safe in all categories of patients, being associated only with rare and negligible local adverse effects; cost-effectiveness is demonstrated-or highly likely-in specific populations of patients with long-term venous access and/or at high risk of dislodgment. CONCLUSION: Subcutaneously anchored securement is a very promising strategy for avoiding dislodgment. Further studies are warranted, in particular for the purpose of defining (a) the best management of the anchoring device so to avoid local problems, (b) the patient populations in which it may be considered highly cost-effective and even mandatory, (c) the possible benefit in terms of reduction of other catheter-related complications such as venous thrombosis and/or infection, and-last but not least-(d) their impact on the workload and stress level of nurses taking care of the devices.

Technical standardization of MIS management of children with pilonidal sinus disease using pediatric endoscopic pilonidal sinus treatment (PEPSiT) and laser epilation.

PURPOSE: This study aimed to standardize the technique of pediatric endoscopic pilonidal sinus treatment (PEPSiT) associated with laser epilation. METHODS: All pediatric patients presenting with acute or chronic pilonidal sinus disease (PSD) who underwent PEPSiT in our institution over a 36-month period (July 2015-July 2018), were included in the study. Pre- and postoperative management, recurrence rate, postoperative pain, hospital stay, analgesic requirements, and patient satisfaction levels were evaluated. RESULTS: A total of 59 patients (23 girls and 36 boys) underwent PEPSiT during the study period. Ten/59 patients (16.9%) had recurrent PSD after open repair, and 4/59 (6.7%) presented a concomitant pilonidal cyst. All children underwent laser epilation pre- and postoperatively over the last 15 months. The average length of surgery was 27.5 min (range 20-45). The average pain score during the first 48 postoperative hours was 2.7 (range 2-5), and the average analgesic requirement was 20 h (range 16-24). The average hospitalization was 22.4 h (range 18-36). At 1 month postoperatively, external openings were healed in all patients. During follow-up, 1 recurrence (1.6%) was recorded and successfully re-treated with PEPSiT. CONCLUSIONS: We believe that PEPSiT represents the technique of choice for treatment of PSD in the pediatric population. It is crucial to standardize the technique consisting of pre- and postoperative laser epilation, PEPSiT, and accurate postoperative wound management with eosin and sulfadiazine spray. LEVEL OF EVIDENCE: Treatment study - Level IV.

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease.

BACKGROUND: Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes. RESULTS: A total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin. CONCLUSIONS: Our results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease.

Autologous fat grafting in the treatment of velopharyngeal insufficiency: Clinical outcomes and treatment tolerability survey in a case series of 21 patients.

INTRODUCTION: Velopharyngeal insufficiency (VPI) is the inability to close the velopharyngeal sphincter during phonation and/or feeding. VPI is clinically characterised by hypernasal speech and nasal regurgitation. In cases of severe VPI, pharyngoplasty is recommended. Cases of mild-to-moderate VPI can be treated with fat grafting of the posterior pharyngeal wall in addition to speech therapy. The lipofilling can also be useful after pharyngoplasty to improve the outcomes. MATERIALS AND METHODS: Twenty-one patients (14 males and 7 females), ages 4-23 affected by mild-to-moderate VPI and treated with lipofilling were included in this retrospective study. The mean injected fat volume was 7.95 cc (median 6 cc, min 4 cc, max 20 cc and range 16 cc). The follow-up ranged from 6 to 60 months. The pre- and post-operative Borel-Maisonny scores were compared using Wilcoxon test. Moreover, we performed a telephone survey with the aim to assess the parental perception on child's speech and quality of life after the surgical treatment. RESULTS: Despite the small sample size, in this case series, we observed a statistically significant Borel-Maisonny score improvement and a parental satisfaction rate of about 85%. CONCLUSIONS: The augmentation of the posterior pharyngeal wall in addition to speech therapy improved the Borel-Maisonny score and the intelligibility of this case series of patients affected by mild-to-moderate VPI. In these patients, evaluated in a multidisciplinary approach, this technique allowed us to avoid major surgical procedures that would modify the anatomy of the velopharyngeal port. However, prospective comparative studies or randomised controlled trials could be useful to compare fat grafting with velopharyngoplasty techniques, with the aim to clarify indications and to define a specific treatment protocol.

Video-Assisted Needle Core Biopsy in Children Affected by Neuroblastoma: A Novel Combined Technique.

Aim This study aims to evaluate the experience gained with video-assisted needle-core biopsy in patients affected by neuroblastoma (NB). Patient and Methods We retrospectively reviewed all the patients presenting at our center with a thoracic, abdominal, and/or pelvic NB who underwent biopsy between 2007 and 2014. Data on demographics, localization, and size of the tumor, image-defined risk factors involved in each case, technical details about biopsies performed, qualitative and quantitative adequacy of tumor sampling and histological diagnosis, postoperative details, and complications were recorded and analyzed. Results During the 7 years of our study 51 patients affected by NB underwent 55 biopsies. Our results focus on the 29 patients undergoing 32 video-assisted needle-core biopsies. The median age was 4 years with a median weight of 13.5 kg. Out of 29, 28 tumors were localized in the abdomen/pelvis compartment, whereas 1 patient presented with a thoracic mass. The median size of the tumors was 57 mm. A total of 28 patients had an adequate tissue sampling for complete tumor characterization. Biopsies were repeated twice in a patient. Three complications occurred in three patients. Conclusions The video-assisted needle-core biopsy combines minimally invasive surgery several advantages with the possibility to obtain multiple samples in different regions with minimal tumor exposition and low complication rate.

Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association.

Congenital anomalies of the kidney and urinary tract (CAKUT) can be associated with Hirschsprung disease (HSCR). Based on the common genetic background of enteric nervous system and kidney development, the reported association of CAKUT and HSCR seems underestimated. Therefore, we designed a prospective study aimed at determining the prevalence of CAKUT in HSCR patients and at identifying RET, glial cell line-derived neurotrophic factor (GDNF), and GDNF family receptor alpha1 (GFRalpha1) mutations or haplotypes associated with this subset of HSCR patients. Eighty-four HSCR patients consecutively admitted to our department between July 2006 and July 2007 underwent interviews, notes review, ultrasound screening (further investigation according to detected anomaly), urinalysis, and DNA extraction for molecular genetics study. Another 27 patients with isolated CAKUT were included as a control group for the molecular genetics study. Twenty-one patients (25%) with HSCR had associated CAKUT, with hydronephrosis and hypoplasia being the most frequent diagnoses. Nine of 21 CAKUT were symptomatic. Six additional patients had other non-CAKUT anomalies (for example, stones, Barter syndrome) that were excluded from association and molecular genetics analysis to avoid bias of inclusion criteria. RET mutations were found in 5 patients (4 HSCR, 1 HSCR + CAKUT, 0 CAKUT) and GDNF mutations in 3 (2 HSCR, 1 CAKUT, 0 HSCR + CAKUT). No GFRalpha1 mutations were found. Finally, the HSCR-predisposing T haplotype of RET proto-oncogene was found in 64% of HSCR, 50% of HSCR + CAKUT, and in 24% of CAKUT patients. The incidence of CAKUT in HSCR patients is 4- to 6-fold higher than expected. Therefore, a patient with HSCR has a 3- to 18-fold higher risk of developing a CAKUT, particularly hydronephrosis or hypoplasia. If we consider that the proportion of predisposing haplotype in HSCR + CAKUT patients resembles that of other syndromic HSCR, we can conclude that HSCR + CAKUT has to be considered a novel syndromic association. These results need to be confirmed in a larger series. At present, we strongly suggest considering ultrasound screening of the urinary tract in every patient with a diagnosis of HSCR.