Artificial Intelligence (AI) Based Analysis of In Vivo Polymers and Collagen Scaffolds Inducing Vascularization.

BACKGROUND/AIM: Biomaterials are essential in modern medicine, both for patients and research. Their ability to acquire and maintain functional vascularization is currently debated. The aim of this study was to evaluate the vascularization induced by two collagen-based scaffolds (with 2D and 3D structures) and one non-collagen scaffold implanted on the chick embryo chorioallantoic membrane (CAM). MATERIALS AND METHODS: Classical stereomicroscopic image vascular assessment was enhanced with the IKOSA software by using two applications: the CAM assay and the Network Formation Assay, evaluating the vessel branching potential, vascular area, as well as tube length and thickness. RESULTS: Both collagen-based scaffolds induced non-inflammatory angiogenesis, but the non-collagen scaffold induced a massive inflammation followed by inflammatory-related angiogenesis. Vessels branching points/Region of Interest (Px^2) and Vessel branching points/Vessel total area (Px^2), increased exponentially until day 5 of the experiment certifying a sustained and continuous angiogenic process induced by 3D collagen scaffolds. CONCLUSION: Collagen-based scaffolds may be more suitable for neovascularization compared to non-collagen scaffolds. The present study demonstrates the potential of the CAM model in combination with AI-based software for the evaluation of vascularization in biomaterials. This approach could help to reduce and replace animal experimentation in the pre-screening of biomaterials.

Cystic Echinococcosis in Hospitalized Children from Western Romania: A 25-Year Retrospective Study.

Cystic echinococcosis (CE) is a cosmopolitan parasitic disease caused by Echinococcus granulosus. We aimed to assess the epidemiological aspects of the disease in hospitalized children from Western Romania, a well-known endemic area for CE. We retrospectively investigated the medical records of children hospitalized between 1998 and 2022. A total of 144 patients were included, and 58.3% were from rural areas. The number of cases increased with age, from 9% in the age group 3-5 years to 59.7% in the age group 11-17 years. The liver was more frequently affected (65.3%), and a significant association between gender and the affected organ was noted; liver cysts were more frequently diagnosed in girls, while lung cysts were recorded mostly in boys. Complications were more frequently reported in patients with pulmonary CE compared to hepatic CE (p = 0.04). Boys had more complications (16/23, 69.6%) compared to girls (7/23, 30.4%) (p = 0.03). A third of the children were hospitalized for more than 14 days, and multiple hospitalizations were recorded in 31.3% of the patients. This paper provides new insights into the epidemiologic features of cystic echinococcosis in children from Western Romania. Our findings indicate that exposure to the parasite starts in childhood, and the rate of hospitalization increases with age. Public health strategies should be implemented and permanently improved in order to lower the prevalence of CE in children.

"Face(s)" of a PHACE(S) Syndrome Patient before and after Therapy: Particular Case Report and Review of Literature.

A rare, uncommon disorder called PHACE(S) (P-posterior fossa anomalies, H-hemangioma, A-arterial anomalies, C-cardiac anomalies, E-eye anomalies, and S-sternal cleft) of unknown etiology was rarely reported. Children are susceptible to developing PHACE(S) syndrome from the moment they are born. It may be challenging for a physician to appropriately diagnose and treat children with PHACE due to the multifaceted nature of the disease and the extensive range of consequences that may be associated with it. A one-month-old newborn girl was admitted to hospital with extensive, multiple facial infantile hemangiomas, ulceration of the lower lip hemangioma-like lesion, cardiovascular, sternal, and neurological concomitant malformations. Five days following the initial application of the medication, systemic treatment with propranolol and topical treatment with silver sulfadiazine produced their first noticeable benefits. The lip ulceration was mostly healed and facial hemangioma started to regress. The regression continued under therapy and this effect persists for 6 months since Propranolol therapy ended. No cardiovascular or neurological clinical events have been registered during follow-up. The present case has three peculiarities: (1) high number of facial hemangiomas; (2) presence of subependymal cyst not yet reported in the literature associated with PHACE syndrome; and (3) lack of cardiovascular events during therapy knowing that these events frequently appear in PHACE syndrome patients.

VEGF Pathway Gene Expression Profile of Proliferating versus Involuting Infantile Hemangiomas: Preliminary Evidence and Review of the Literature.

Background. Infantile hemangiomas may have unexpected behavior. Initial regression (spontaneously or drug-induced) may be followed by unexplained recurrences. At this moment, there are no well-established criteria to predict infantile hemangioma reccurrences. Methods. We compared the VEGF pathway gene expression profile for one case of involuting infantile hemangioma versus one case of recurrent proliferative infantile hemangioma using TaqMan Array. Results. We found ten genes upregulated for both involuting and recurrent proliferative hemangiomas: ACTB, KRAS, MAP2K1, HRAS, NOS3, BAD, HSPB1, HPRT1, GUSB, and CASP9. Thirteen genes were downregulated for both involuting and proliferative hemangiomas: FIGF, ACTG1, GRB2, MAPKAPK2, ACTG2, MAP2K2, MAPK3, HSP90AA1, MAP2K6, NRAS, ACTA1, KDR, and MAPK1. Three genes showed divergent expression between proliferating and involuting hemangiomas. Proliferating hemangioma had MAPK14 and AKT1 gene upregulation and ACTA2 downregulation. Involuting infantile hemangioma was characterized by ACTA2 upregulation and AKT1 and MAPK14 downregulation. Conclusions. Three genes, AKT1, p38/MAPK14, and ACTA2, were found to have divergent expression in proliferating and involuting infantile hemangiomas. Excepting AKT1, which was mentioned in the last ISSVA classification (strictly related to Proteus Syndrome), none of the other genes were reported. An accurate gene expression profile mapping of infantile hemangiomas together with a gene expression-based hemangioma classification is stringently needed.

Costal cartilage overgrowth does not induce pectus-like deformation in the chest wall of a rat model.

Overgrowth of the costal cartilages has been frequently reported to be an etiological factor of chest wall deformities in children. The present study aimed to investigate if induced overgrowth of the costal cartilages could lead to deformation of the chest wall in a rat model. An insulin-like growth factor 1 (IGF1) solution was directly injected under the perichondrium of the last three costal cartilages of 2-week-old rat pups. Two different concentrations, 50 µg/ml (E50) and 100 µg/ml (E100), were applied. This procedure was repeated once per week for 5 consecutive weeks. Subsequently, 14 days after the last injection, all animals were euthanized before the shape of the thoracic cage was assessed, and the diameter was measured. In addition, the last three costal cartilages were dissected before the samples were prepared and examined by light microscopy. Rats that received E100 exhibited larger sagittal and coronal rib cage diameters compared with those in the E50 and control groups. However, no deformation could be observed in the chest wall. Microscopic examinations revealed an anabolic pattern in the E100 group. The present findings suggested that locally administered IGF1 stimulated cell proliferation and tissue growth in coastal cartilages in a dose-dependent manner in vivo. However, this induced overgrowth of the costal cartilages did not result in the deformation of the chest wall.

Expression of ß1 adrenergic receptor in vascular anomalies in children.

OBJECTIVE: Controversial, heterogeneous, and inconsistent responses to beta-blockers have been reported in some cases of infantile proliferative hemangiomas. On the basis of these clinical observations, we aimed to examine the ß1 adrenergic receptor (ß1-AR) protein expression distribution among different types of pediatric vascular anomalies. METHODS: Immunohistochemistry (IHC) was performed for ß1-AR on 43 surgical specimens. RESULTS: We found positive ß1-AR IHC staining in all intramuscular hemangiomas, capillary-lymphatic, lymphatic, venous, and combined malformations, and Masson's tumor cases, as well as in 7 of 10 cases of proliferative infantile hemangiomas. CONCLUSIONS: Our research demonstrates, for the first time, the degree of heterogeneous expression of ß1-AR among pediatric vascular malformations. Our results support the need for ß1-AR assessment in pediatric vascular anomalies to select cases with a robust response to ß1-selective blockers. ß1-AR assessment may have a strong impact on therapeutic refinement for pediatric vascular anomalies by selecting cases with a stronger response to beta-blockers.

Combined Staged Surgery and Negative-Pressure Wound Therapy for Closure of a Giant Omphalocele.

The management of giant omphaloceles had always been a point of interest for the pediatric surgeons. Many surgical techniques were proposed, but none of them succeeded to become the standard procedure in closing the congenital abdominal defect. We present a case of giant omphalocele in which we used staged surgical closure combined with a prosthetic patch, with negative-pressure therapy and, finally, definitive surgical closure. Even though a major complication occurred during the treatment, we were able to close the defect without any prosthetic material left in place.

Role of imagistic techniques in diagnosing soft-tissue vascular anomalies in pediatric population - a 5-year experience.

Soft-tissue vascular anomalies have a worldwide estimated prevalence of 4.5% in the pediatric population. From January 1, 2014 until December 31, 2018, imagistic and histological evaluations were performed in 214 patients aged between one day and 18 years old, who were diagnosed with different soft-tissue vascular anomalies in our Center. From the 214 patients included in the study, 36.45% (n=78) were males, 63.55% (n=136) were females and 37.38% (n=80) of the patients were less than one year of age at time of admission. Infantile hemangioma was the most frequent type of soft-tissue vascular anomaly (35.51%) and the face was the most frequent affected region (25.7%). Ultrasound (US) examination is the most used imaging technique due to its wide accessibility and for providing valuable information about the anatomical localization of the lesions, the type of vessels involved, distribution and density of vascularization. Magnetic resonance imaging (MRI) can be used for assessing the extent of deep or large lesions, but it usually requires anesthesia. Computed tomography (CT) is useful when patients present contraindications to anesthesia and it has the advantage of a shorter image acquisition time. Histological studies have an important role in establishing the diagnosis even for the atypical cases of soft-tissue vascular anomalies. Furthermore, the prognosis depends on the histological type. In conclusion, there is a need for collaboration between the clinician, radiologist, pathologist and surgeon in order to establish a precise diagnosis and therapeutic strategy for each patient.

Acute limb ischemia in neonates: etiology and morphological findings - short literature review.

The acute limb ischemia (ALI) in neonates is a rare phenomenon, but with serious consequences if undiagnosed or untreated. The purpose of this review is to briefly present the etiology of ALI and morphological findings in correlation with specific causes. Etiology can be classified into two main groups: prenatal (in utero compression, thrombosis and embolism) and postnatal (iatrogenic, thromboembolism and vascular malformations). The most common cause of ALI is catheter-related thrombosis (almost 90% of thrombosis cases are associated with catheter use), but other rare causes like vascular malformations should not be overlooked. Ultrasound represents a non-invasive, inexpensive and widely available imaging technique, which provides sufficient information to evaluate the situation and establish proper therapeutic strategies. Morphological tests do not represent the standard diagnostic procedure in ALI, but they can provide useful information. The findings depend on the etiology: intraluminal thrombi, vascular changes, placental pathological modifications. Every morphological result must be correlated with the clinical picture and imagistic findings. In conclusion, ALI in neonates is a rare condition, usually associated with catheter use in intensive care unit setting, with multiple risk factors and conditions that increase the risk of occurrence.