The Use of Thoracoscopic Release in the Surgical Correction of Thoracic Scoliosis in Children.

INTRODUCTION: Recently, the use of thoracoscopic methods in spinal deformity surgery has increased, however, the issue of the effectiveness of combining anterior release with posterior spinal fusion compared to single-stage posterior instrumentation remains controversial, which raises the issue of the effectiveness and feasibility of their use. PURPOSE: To evaluate the effectiveness of endoscopic anterior release for thoracic scoliosis in children. MATERIAL AND METHOD: A retrospective analysis of the results of surgical treatment of 48 patients with idiopathic scoliosis of the thoracic spine aged 12-17 years, with a thoracic curve of more than 60°, was carried out. To determine the stability of deformity, the stability index according to A.I. Kazmin was used. (SI) defined as the ratio of the angle of deformity in the supine position to the angle of deformity in the standing position. Indications for anterior release were incomplete skeletal growth and relatively stable deformities (SI 0.75-0.85). Group 1 included 27 patients operated on in one stage without anterior release, and group 2 included 21 patients in two stages, with preliminary anterior release using video-assisted thoracoscopy. RESULTS: In group 1, the average Cobb angle of deformity was 71.8° with an average stability index of 0.8. In the second group, the average cobb angle of deformity was 69.7°, the average stability index was 0.82. In group 1 after surgery, the average Cobb angle was 27.8°, with an average correction of 63.39%. In the second group, the postoperative deformity angle was 17.4°, the average correction was 76.26%. Thus, we found a statistically significant increase in postoperative correction when using a combined anterior/posterior approach (p < 0.05). CONCLUSION: In the study, in patients with relatively stable deformities, a statistically significant increase in the degree of postoperative correction was revealed (p < 0.05) when using a combined anterior/posterior approach. Performing an anterior thoracoscopic release for thoracic deformities can improve long-term results due to the formation of 360° spinal fusion at the apex of the deformity, as well as turning off the pathogenetic links in the progression of the deformity. LEVEL OF EVIDENCE: III.

Surgical Treatment of Portal Hypertension in Children.

Introduction: Portal hypertension is a syndrome characterized by increased pressure in the portal vein system and can be caused by impaired blood flow in the portal vein, hepatic veins, or inferior vena cava. The main complications of this condition are bleeding from varicose veins of the esophagus (in our study in 100% of patients), splenomegaly with hypersplenism (in our study in 98% of patients), ascites (in our study in 1 patient). The main goal of treating portal hypertension is to prevent bleeding from esophageal varices. However, today the goal of surgical treatment of portal hypertension in children is not only to prevent the development of bleeding but also the possible restoration of intrahepatic blood flow. Materials and Methods: A retrospective analysis of the results of treatment of portal hypertension in 75 children (41 boys, 34 girls) operated in our Center for the period from 2019 to 2022 was carried out. The mean age of the patients was 7 ± 1 years. Sixty-nine patients had an extrahepatic form of portal hypertension, and 6 patients had an intrahepatic form (liver fibrosis). In 14 patients (18.6%), the operation was repeated (a vascular shunt was previously applied in another hospital; 4 children were operated on repeatedly). Results: A good result was obtained in all children, and the risk of bleeding from varicose veins of the esophagus was eliminated. Vascular bypass surgery was performed in all cases: mesoportal bypass in 17 (22.7%) patients, splenorenal bypass in 37 (49.3%) patients, mesocaval bypass in 21 (28%) patients. In 10 (13%) cases, repeated bypass surgery was required due to dysfunction or thrombosis of the previously performed bypass. In 14 (18.6%) patients with mesoportal shunts, blood flow in the liver was completely restored. Conclusions: The main method of surgical treatment of portal hypertension today is portosystemic bypass surgery, which effectively prevents bleeding from varicose veins of the esophagus. Mesoportal shunting is a definitive treatment for extrahepatic portal hypertension that restores portal perfusion of the liver.

Our experience of using Losartan for esophageal stenosis in children with dystrophic form of congenital epidermolysis bullosa.

INTRODUCTION: Dystrophic epidermolysis bullosa (DEB) is one of the most severe forms of congenital epidermolysis bullosa and characterized by the formation of many surgical complications. Esophageal stenosis is a common complication of DEB and occurs in almost 76% of cases. Balloon dilatation (BD) under X-ray control is the main therapeutic technique, however conservative treatment is necessary to prevent restenosis. The use of the drug losartan is promising due to its antifibrotic effect through the suppression of transforming growth factor-ß1 (TGF-ß1). PURPOSE: To evaluate the efficacy of losartan in the prevention of restenosis after BD of esophageal stenosis in children with DEB. MATERIALS AND METHODS: The study included 19 children from 2 to 16 years old (mean age 9.2 ± 3.58 years) with DEB and X-ray confirmed esophageal stenosis. All children underwent BD. In the main group 9 children after BD have received losartan, in the control group of 10 children - only standard therapy. The observation period was 12 months. RESULTS: In the main group, 1 child (11.1%) required repeated dilatation, in the control group - 4 children (40%). Indicators of nutritional deficiency (THINC scale) and the disease severity index (EBDASI) were significantly lower in the group of children treated with losartan. No undesirable actions of the drug were recorded. CONCLUSIONS: In this study losartan showed its safety, contributed to a decrease in the restenosis frequency and an improvement in the nutritional status of children with DEB after BD. However, further studies are required to confirm its effectiveness. LEVEL OF EVIDENCE: IV.

Surgical Treatment of Patients with Full Tracheal Rings: Our Experience.

Introduction: Complete tracheal rings are a rare pathology occurring in 1 out of 100,000 live births. It is rare isolated tracheal or tracheobronchial anomaly resulting from abnormal cartilage growth, forming a complete ring, and leading to airway stenosis. A sliding tracheoplasty, primarily described by Tsang et al. and later widely presented by Grillo et al., overlaps the tracheal stenosing segments and shortens the trachea itself, and thus increases the diameter and circumference of the stenosing area double up. Materials and Methods: We have performed four slide tracheoplasties in the period between February 2019 and December 2020 in children who underwent medical treatment in the department of thoracic surgery in our center. Median age was 10 ± 5.5 months (2 months-1 year 6 months). Median weight was 6.9 ± 1.9 kg (4.5-9 kg). Slide tracheoplasty was performed using central venoarterial extracorporeal membrane oxygenation in 3 cases and using cardiopulmonary bypass in 1 case. Results: Patients were on artificial lung ventilation for 2-6 days in the postoperative period. Patients were discharged 14-18 days after the surgery. There were no lethal outcomes in our study. Discussion: Long segment congenital tracheal stenosis is an often and serious life-threatening anatomical malformation that bounded the length of trachea >50%. There is no unique treatment strategy for patients with such pathology. Sliding tracheoplasty can be recommended for all, but not for the shortest segments of stenosis, as it creates permissible voltage fluctuations during tracheal anastomosis. Excellent results in management of such severe patients can be achieved only through the collaboration of multidisciplinary team of specialists sharing organized and consistent patient-oriented approach.

Clinical, Morphological, and Immunohistochemical Justification of Surgery for Chronic Appendicitis in Children.

Objective: Chronic appendicitis (CA) is a diagnosis characterized by long-standing right lower quadrant pain. We analyzed clinical, morphological, and immunohistochemical studies of the appendix to confirm the adequacy of surgery for CA in children with chronic right lower quadrant pain. Patients and Methods: We carried out comparative studies of clinical presentations and results of morphological and immunohistochemical studies of remote appendicitis in 55 children with chronic recurrent lower quadrant pain (CRLQP). Results: Morphological and immunohistochemical studies revealed three types of changes in the appendix. Type 1 (n = 21)-chronic inflammation. Inflammatory leukocyte infiltration was localized within the mucous membrane of the appendix. An immunohistochemical study revealed a significant (P < .01) increase in the expression of CD106 (vascular cell adhesion molecule 1) and in the number of matrix metalloproteinase 9 (MMP-9) positive cells. Type 2 (n = 20)-lymphoid hyperplasia. Morphological changes were characterized by lymphoid infiltration of the mucosa and submucosa of the appendix. Immunological changes were characterized by an increase (P < .01) in the expression and number of MMP-9, expression of CD106 positive cells, an increase in the expression of collagen IIIα in combination with a decrease in the expression and number of positive vascular endothelial growth factor (VEGF) and vasoactive intestinal peptide cells. Type 3 (n = 12)-catarrhal inflammation. Morphological changes were characterized by impaired blood circulation only in the mucous membrane, without destructive or inflammatory changes. Immunological changes were characterized by an increase (P < .01) in the expression and number of VEGF-positive cells, which may indicate a response to local hypoxia of the appendix and explain neovascularization in a chronic condition. The abdominal syndrome after appendectomy was noted to disappear in 89% of patients. The established changes in remote appendicitis, other than acute inflammation, make it possible to consider reasonable appendectomy a way of treating CRLQP in children. Conclusions: We have identified immunohistochemical and morphological changes pointing to autoimmune and vascular mechanisms of appendix damage in children with CRLQP. Laparoscopic appendectomy helps to eliminate abdominal pain in most CA patients.

Apurinic/apyrimidinic endonuclease Apn1 from Saccharomyces cerevisiae is recruited to the nucleotide incision repair pathway: Kinetic and structural features.

Apurinic/apyrimidinic endonuclease Apn1 of Saccharomyces cerevisiae is known as a key player of the base excision DNA repair (BER) pathway in yeast. BER is initiated by DNA glycosylases, whereas Apn1 can start DNA repair individually in the nucleotide incision repair (NIR) pathway. The aim of this research was to elucidate kinetic and structural dynamic aspects of Apn1 involvement in the NIR process. One of the key characteristics of AP endonuclease's interactions is known to be divalent metal ions playing a part of a cofactor. Well-studied human APE1 employs Mg2+ ions, with metal ion concentration's affecting enzymatic activity exerted by APE1. In our study, we aimed to test the effect of the Mg2+ ion on Apn1's NIR catalysis by examining structural dynamics of DNA during the interaction in real time using the stopped-flow technique. To test NIR activity of Apn1, deoxyribooligonucleotide duplexes containing a 5,6-dihydro-2'-deoxyuridine (DHU) residue were employed as substrates. A 2-aminopurine (2-aPu) residue was a reporter group fluorescence intensity of which was detected during Apn1-DNA interactions. NIR activity of both WT and H83A Apn1 was found to be arrested during the interaction with a DNA duplex containing the 2-aPu residue upstream of DHU. We conducted molecular dynamics simulations to elucidate the structural features of complexes of the enzyme with DHU-containing DNAs. The NIR recruiting S. cerevisiae Apn1 proceeds via multistep rearrangements of the complex of Apn1 with a DHU-containing DNA substrate and results in the incised product of the reaction. For wild-type Apn1, the catalytic rate constants do not depend on the Mg2+ concentration, i.e., they are equal in NIR and BER buffers, with equilibrium association constant Ka being 10-fold higher in NIR buffer. Our data reveal more delicate regulation of Apn1's NIR activity due to the more complicated kinetic mechanism, as compared to BER.

Data on PAGE analysis and MD simulation for the interaction of endonuclease Apn1 from Saccharomyces cerevisiae with DNA substrates containing 5,6-dihydrouracyl and 2-aminopurine.

This article presents new data on nucleotide incision repair (NIR) activity of apurinic/apyrimidinic endonuclease Apn1 of Saccharomyces cerevisiae, which is known as a key player of the base excision DNA repair (BER) pathway, see "Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV" [1], "Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae" [2] and "Characterisation of new substrate specificities of Escherichia coli and Saccharomyces cerevisiae AP endonucleases" [3]. The characterization of NIR activity of wild type Apn1 and mutant form Ape1 H83A were made by denaturing PAGE analysis, and MD simulations of Apn1 complexed with DNA containing 5,6-dihydro-2'-deoxyuridine (DHU) and 2-aminopurine (2-aPu) residues. This data article is associated to the manuscript titled "Apurinic/apyrimidinic endonuclease Apn1 from Saccharomyces cerevisiae is recruited to the nucleotide incision repair pathway: kinetic and structural features" [4]. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic incision of abasic sites in DNA.

BACKGROUND: The apurinic/apyrimidinic (AP) endonuclease Apn1 from Saccharomyces cerevisiae is a key enzyme involved in the base excision repair (BER) at the cleavage stage of abasic sites (AP sites) in DNA. The crystal structure of Apn1 from S. cerevisiae is unresolved. Based on its high amino acid homology to Escherichia coli Endo IV, His-83 is believed to coordinate one of three Zn2+ ions in Apn1's active site similar to His-69 in Endo IV. Substituting His-83 with Ala is proposed to decrease the AP endonuclease activity of Apn1 owing to weak coordination of Zn2+ ions involved in enzymatic catalysis. METHODS: The kinetics of recognition, binding, and incision of DNA substrates with the H83A Apn1 mutant was investigated. The stopped-flow method detecting fluorescence intensity changes of 2-aminopurine (2-aPu) was used to monitor the conformational dynamics of DNA at pre-steady-state conditions. RESULTS: We found substituting His-83 with Ala influenced catalytic complex formation and further incision of the damaged DNA strand. The H83A Apn1 catalysis depends not only on the location of the mismatch relative to the abasic site in DNA, but also on the nature of damage. CONCLUSIONS: We consider His-83 properly coordinates the active site Zn2+ ion playing a crucial role in catalytic incision stage. Our data prove suppressed enzymatic activity of H83A Apn1 results from the reduced number of active site Zn2+ ions. GENERAL SIGNIFICANCE: Our study provides insights into mechanistic specialty of AP site repair by yeast AP endonuclease Apn1 of Endo IV family, which members are not found in mammals, but are present in many microorganisms. The results will provide useful guidelines for design of new anti-fungal and anti-malarial agents.