Case Report: An early-onset inflammatory colitis due to a variant in TNFAIP3 causing A20 haploinsufficiency.

Autoinflammatory diseases (AID) are a heterogeneous group of inherited conditions caused by abnormal activation of systems mediating innate immunity. Recent literature focuses on A20 Haploinsufficiency, an autoinflammatory disease with a phenotype resembling Behçet disease (BD). It is caused by loss-of-function mutations in TNFAIP3 gene that result in the activation of a pro-inflammatory pathway. In this case report we describe a one-year-old baby who came to our attention for hematochezia appeared at three months of age which was considered an expression of early-onset colitis. The following appearance of cutaneous inflammation Behçet-like and the positive family history concurred with the diagnosis of an autoinflammatory disease. Extended genetic tests in the patient allowed to identify a heterozygous variant in TNFAIP3 [NM_006290.4:c.460G > T, p.(Glu154Ter)], not previously described and not present in the GnomAD database. As a consequence the diagnosis A20 Haploinsufficiency was established and the appropriate management was started. The same TNFAIP3 variant was also found in her father who had suffered from recurrent oral aphthosis, vitiligo and thyroiditis since childhood. In conclusion, we described a young patient with a novel heterozygous mutation in TNFAIP3 who developed BD-like symptoms. We proposed that loss-of-function variants in TNFAIP3 may be associated with a very early-onset intestinal BD phenotype.

Decellularized esophageal tubular scaffold microperforated by quantum molecular resonance technology and seeded with mesenchymal stromal cells for tissue engineering esophageal regeneration.

Current surgical options for patients requiring esophageal replacement suffer from several limitations and do not assure a satisfactory quality of life. Tissue engineering techniques for the creation of customized "self-developing" esophageal substitutes, which are obtained by seeding autologous cells on artificial or natural scaffolds, allow simplifying surgical procedures and achieving good clinical outcomes. In this context, an appealing approach is based on the exploitation of decellularized tissues as biological matrices to be colonized by the appropriate cell types to regenerate the desired organs. With specific regard to the esophagus, the presence of a thick connective texture in the decellularized scaffold hampers an adequate penetration and spatial distribution of cells. In the present work, the Quantum Molecular Resonance® (QMR) technology was used to create a regular microchannel structure inside the connective tissue of full-thickness decellularized tubular porcine esophagi to facilitate a diffuse and uniform spreading of seeded mesenchymal stromal cells within the scaffold. Esophageal samples were thoroughly characterized before and after decellularization and microperforation in terms of residual DNA content, matrix composition, structure and biomechanical features. The scaffold was seeded with mesenchymal stromal cells under dynamic conditions, to assess the ability to be repopulated before its implantation in a large animal model. At the end of the procedure, they resemble the original esophagus, preserving the characteristic multilayer composition and maintaining biomechanical properties adequate for surgery. After the sacrifice we had histological and immunohistochemical evidence of the full-thickness regeneration of the esophageal wall, resembling the native organ. These results suggest the QMR microperforated decellularized esophageal scaffold as a promising device for esophagus regeneration in patients needing esophageal substitution.

Guidelines of the Italian Society of Videosurgery in Infancy (SIVI) for the minimally invasive treatment of fetal and neonatal ovarian cysts.

In the last three decades, fetal ovarian cysts were diagnosed more frequently, due to technological improvement and the increasing use of prenatal screening ultrasound. Nonetheless, treatment uncertainties are still present, either prenatally or postnatally. Recently, significant innovations on diagnosis and treatment have been proposed and a more conservative, minimally invasive approach may be offered to the Pediatrician or the Surgeon who face with this condition during prenatal or neonatal age. (...).

Guidelines of the Italian Society of Videosurgery (SIVI) in Infancy for the minimally invasive treatment of Hypertrophic Pyloric Stenosis in neonates and infants.

The most appropriate treatment for the infantile Hypertrophic Pyloric Stenosis (HPS) is still debated. The non-surgical conservative treatment with oral or intravenous administration of atropine does not enjoy a widespread appreciation for several factors (...).

Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model.

BACKGROUND: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. METHODS: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). RESULTS: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. CONCLUSIONS: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after seeding. The substitute was able to recapitulate in shape and function the original esophageal muscle layer.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia.

Esophageal Atresia (EA) is defined as an interruption in esophageal continuity that results in a proximal tract that ends in a blind pouch in 98% of cases, and a distal tract that in 87% of cases arises via a Fistula from the Trachea (TEF). (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of pediatric nephrectomy and partial nephrectomy.

Throughout history, the pediatric laparoscopic nephrectomy was first described at the beginning of the Nineties by Erlich and colleagues in a child and by Koyle and colleagues in an unweaned patient. (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the ureteropelvic-junction obstruction.

The hydronephrosis, characterized by the dilation of the renal pelvicalyceal system with possible functional damage to the renal parenchyma, is the most common congenital abnormality of the urinary system detected in utero through the prenatal ultrasound screening. (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia.

Not available.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the ureteropelvic-junction obstruction.

Not available.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of pediatric nephrectomy and partial nephrectomy.

Not available.

Meckel's diverticulum and bowel obstruction due to phytobezoar: a case report.

Meckel's diverticulum is a common anomaly of the gastrointestinal tract. The most common complications of Meckel's diverticulum are inflammation, bleeding and obstruction. We present a 12-year-old boy with bowel obstruction due to phytobezoar in a Meckel's diverticulum. We describe diagnostic difficulties and our surgery approach comparing it to the literature.

In vitro and in vivo proposal of an artificial esophagus.

Artificial materials and autologous tissues used for esophageal reconstruction often induce complications like stenosis and leakage at long-term follow-up. This study evaluates the possibility to obtain in vitro an implantable tissue-engineered esophagus composed of homologous esophageal acellular matrix and autologous smooth muscle cells (SMCs). Acellular matrices obtained by detergent-enzymatic method did not present any major histocompatibility complex marker and expressed bFGF as protein, showing angiogenic activity in vivo on the chick embryo chorioallantoic membrane (CAM). Moreover, they supported cell adhesion, and inasmuch as just after 24 h from seeding, the scaffold appeared completely covered by SMCs. To verify the biocompatibility of our constructs, defects created in the porcine esophageal wall were covered using homologous acellular matrices with and without cultures of autologous SMCs. At 3 week from surgery, the patches composed of only acellular matrices showed a more severe inflammatory response and were negative for alpha-smooth muscle actin immunostaining. In contrast, the cell-matrix implants presented ingrowth of SMCs, showing an early organization into small fascicules. Collectively, these results suggest that patches composed of homologous esophageal acellular matrix and autologous SMCs may represent a promising tissue-engineering approach for the repair of esophageal injuries.

Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue-engineering approach to abdominal wall-defect repair.

Myoblasts were obtained by culturing in vitro, single muscle fibers, isolated by enzymatic digestion from rat flexor digitorum brevis, and their phenotype was confirmed by myogenic differentiation factor, myogenic factor-5, myogenin and desmin. Cultured myoblasts were harvested and seeded on patches of homologous acellular matrix, obtained by detergent-enzymatic treatment of abdominal muscle fragments. Myoblast-seeded patches were inserted between obliqui abdominis muscles on the right side of 1-month-old rats, while non-seeded patches were implanted on the left side. Thirty days after surgery, non-seeded patches were completely replaced by fibrous tissue, while the structure of myoblast-seeded patches was well preserved until the 2nd month. Seeded patches displayed abundant blood vessels and myoblasts, and electromyography evidenced in them single motor-unit potentials, sometimes grouped into arithmic discharges. Ninty days after implantation, the thickness of myoblast-seeded patches and their electric activity decreased, suggesting a loss of contractile muscle fibers. In conclusion, the present results indicate that autologous myoblast-homologous acellular muscle matrix constructs are a promising tool for body-wall defect repair, and studies are under way to identify strategies able to improve and maintain the structural and functional integrity of implants for longer periods.

Autologous satellite cell seeding improves in vivo biocompatibility of homologous muscle acellular matrix implants.

Acellular matrix obtained from homologous muscular tissue has been previously used to repair muscular defects. However, the implants, although not rejected, give rise to an intense inflammatory response and are rapidly replaced by fibrous tissue. In this study we examined the possibility that co-culture with autologous satellite cells can improve the efficiency of homologous acellular matrix as skeletal muscle substitute. Satellite cells, isolated from rat dorsal muscle, were cultured in vitro on homologous acellular matrix obtained by detergent-enzymatic treatment of abdominal muscle fragments. Scanning electron microscopy revealed that after 24 h of co-culture satellite cells were attached to the matrix, but still possessed a round shape. After 96 h, seeded cells began to flatten and to differentiate, originating few multinucleated myotubes. Patches of homologous matrix, seeded or not with autologous satellite cells, were implanted in the dorsal muscle of rats. At autopsy, the implants were recovered and processed for light microscopy. Two weeks after surgery, fibrous tissue started to replace the grafts composed only by acellular matrix, which at the 4th week were transformed into a fibrous scar. In contrast, at both times post-surgery the structure of implants containing autologous satellite cells was well preserved. The inflammatory reaction was modest and fibrosis was confined to the periphery of the grafts. It is concluded that the presence of autologous satellite cells is an important factor to preserve the structural integrity and to improve in vivo biocompatibility of homologous muscular acellular matrix implants.