A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic.

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic-ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.

The effects of antibiotic therapy on neonatal sepsis-associated acute kidney injury.

AIM: Neonatal sepsis remains one of the most dangerous conditions in the neonatal intensive care units. One of the organs affected by sepsis is the kidney, making acute kidney injury (AKI) a common complication of sepsis. Treatment of sepsis almost always involves antibiotic therapy, which by itself may cause some adverse effects, including nephrotoxicity. We analyzed the mutual effect of antibiotic therapy and sepsis on AKI in an experimental and clinical study in infants and neonatal rats. MATERIALS AND METHODS: We evaluated the influence of therapy with different antibiotics on the appearance of AKI markers (blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), clusterin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), calbindin, glutation-S-transferase subtype π (GST-π)) and liver injury markers in newborns with or without clinical signs of sepsis in the intensive care unit. In parallel, we analyzed the development of AKI in experimental lipopolysaccharide (LPS)-induced systemic inflammation in newborn rats accompanied by antibiotic therapy. KEY FINDINGS: We showed that therapy with metronidazole or ampicillin in combination with sulbactam had a beneficial effect in children with suspected sepsis, resulting in a decrease in AKI markers levels. However, treatment of newborns with netilmicin, cefepime, linezolid, or imipenem in combination with cilastatin worsened kidney function in these patients. SIGNIFICANCE: This prospective study indicates which antibiotics are preferable in neonatal sepsis and which should be used with caution in view of the risk of AKI development.

Encouraging Young Pediatric Surgeons and Evaluation of the Effectiveness of a Pediatric Endosurgery Workshop by Self-Assessment and an Objective Skill Validation System.

Background: Japanese pediatric endosurgery experts conducted a workshop for young pediatric surgeons in Russia in collaboration with Russian expert pediatric surgeons. This study was aimed to develop a contributive workshop program and evaluate its impact on young pediatric surgeons. Methods: A 2-day pediatric endosurgery workshop was held in Moscow in February 2020. After conducting a needs assessment survey, Japanese and Russian faculties developed the workshop contents, including pre- and postworkshop skills assessments, lectures, and hands-on training. Skills assessments were performed using the objective skill validation system, the "A-Lap Mini," mimicking intestinal anastomosis. The trainees self-evaluated their knowledge and skills using a five-point scale. Results: Fifteen novice trainee participated and 14 (93.3%) completed the workshop program. The completion rate for the suturing task before and after the workshop was 40.0% (6/15) and 85.7% (12/14), respectively. The following five skill evaluation criteria, which were objectively evaluated: performance time changed from 751.6 ± 247.1 seconds to 780.0 ± 313.3 seconds (P > .05), number of full-thickness sutures improved from 1.0 ± 1.41 to 2.64 ± 0.84 (P = .003), area of wound-opening changed from 0.42 ± 0.83 mm2 to 0.53 ± 1.13 mm2 (P > .05), suture tension improved from 55.48% ± 19.51% to 61.95% ± 23.91% (P > .05), and maximum air leakage pressure improved from 3.76 ± 2.11 kPa to 8.42 ± 7.68 kPa (P > .05). Regarding the self-assessed questionnaire administered before and after the workshop, the confidence in endosurgery skills significantly improved as follows: forceps manipulation ability improved from 2.7 to 3.7 (P < .05), and suturing performance improved from 2.5 to 3.6 (P < .05). The usefulness of the workshop for clinical surgery was scored at 4.3. Conclusions: Quantitative skill evaluation with an automatic feedback function was useful for endosurgery training. Delivering feedback concerning the assessment results to the trainee helps them to determine the specific training requirements needed for clinical endosurgery.

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot.

The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0-1025.5/106 cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.