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Introduction: Immunometabolism is essential factor of tumor progression, and tumor-associated macrophages are characterized by substantial changes in their metabolic status. In this study for the first time, we applied targeted amino acid LC-MS/MS analysis to compare amino acid metabolism of circulating monocytes isolated from patients with breast, ovarian, lung, and colorectal cancer., Methods: Monocyte metabolomics was analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) analysis of amino acid extracts. The targeted analysis of 26 amino acids was conducted by LCMS/MS on an Agilent 6460 triple quadrupole mass spectrometer equipped with an electrospray ionization source and an Agilent 1260 II liquid chromatograph., Results: Comparison of monocytes of cancer patients with monocytes of healthy control individuals demonstrated that in breast cancer most pronounced changes were identified for tryptophan (AUC = 0.76); for ovarian cancer, aminobutyric acid was significantly elevated (AUC= 1.00); for lung cancer significant changes we indented for citrulline (AUC = 0.70). In order to identify key amino acids that are characteristic for monocytes in specific cancer types, we compared each individual cancer with other 3 types of cancer. We found, that aspartic acid and citrulline are specific for monocytes of patients with colorectal cancer (p<0.001, FC = 1.40 and p=0.003, FC = 1.42 respectively). Citrulline, sarcosine and glutamic acid are ovarian cancer-specific amino acids (p = 0.003, FC = 0.78, p = 0.003, FC = 0.62, p = 0.02, FC = 0.78 respectively). Glutamine, methionine and phenylalanine (p = 0.048, FC = 1.39. p = 0.03, FC = 1.27 and p = 0.02, FC = 1.41) are lung cancer-specific amino acids. Ornithine in monocytes demonstrated strong positive correlation (r = 0.63) with lymph node metastasis incidence in breast cancer patients. Methyl histidine and cysteine in monocytes had strong negative correlation with lymph node metastasis in ovarian cancer patients (r = -0.95 and r = -0.95 respectively). Arginine, citrulline and ornithine have strong negative correlation with tumor size (r = -0.78, citrulline) and lymph node metastasis (r = -0.63 for arginine and r = -0.66 for ornithine)., Discussion: These alterations in monocyte amino acid metabolism can reflect the reaction of systemic innate immunity on the growing tumor. Our data indicate that this metabolic programming is cancer specific and can be inhibiting cancer progression. Cancer-specific differences in citrulline, as molecular link between metabolic pathways and epigenetic programing, provide new option for the development and validation of anti-cancer therapies using inhibitors of enzymes catalyzing citrullination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chagovets, Starodubtseva, Tokareva, Novoselova, Patysheva, Larionova, Prostakishina, Rakina, Kazakova, Topolnitskiy, Shefer, Kzhyshkowska, Frankevich and Sukhikh.)

Objective: To evaluate the quality of life before and after video-assisted thoracoscopic plication of relaxed dome of diaphragm., Material and Methods: The study included 17 patients operated on for unilateral relaxation of diaphragm. We analyzed quality of life in preoperative period, 1, 3, 6 and 12 months after surgery using the SF-36 and EuroQ-5D-5L questionnaires. To assess the impact of abnormality on respiratory function, we estimated diaphragm position, spirometry data and SGRQ scores., Results: FVC increased by 16.5% after 1 month, 19.5% after 6 months and 20.1% after 12 months. In addition, FEV1 significantly increased (by 12.6% after 1 month, 10.1% after 6 months and 12.7% after 12 months). Mean values of diaphragm elevation in postoperative period decreased by 25.5-25.6%. According to the SF-36 and EuroQ-5D-5L questionnaires, physical and psychological health components significantly increased within a month after surgical treatment. According to the SGRQ questionnaire, influence of disease on overall status decreased a month after surgery as evidences by lower total score ( p <0.05)., Conclusion: Objective and survey data revealed significant improvement in quality of life after surgery. A trend towards higher quality of life was demonstrated by all questionnaires in a month after surgery.

Modern guidelines have identified thoracoscopic thymectomy as a preferable option for myasthenia gravis and non-invasive thymoma. In the era of the new coronavirus infection, it is relevant to develop protocols for anesthetic and perioperative support of patients undergoing thymectomy for myasthenia gravis after COVID-associated pneumonia (CAP). We present the results of thoracoscopic thymectomies in patients after CAP. Multidisciplinary team should determine therapeutic support, the need for plasmapheresis and thymectomy. Plasmapheresis and glucocorticosteroids are effective in addition to anticholinesterase therapy at the stages of perioperative support for correction of neurological status in patients with myasthenia combined with chronic obstructive pulmonary disease and pulmonary hypertension. Outpatient direct anticoagulants are advisable considering the need for prolonged postoperative prevention of thrombotic events.

Introduction: Variants in the BRCA1/2 genes are responsible for familial breast cancer. Numerous studies showed a different spectrum of BRCA variants among breast cancer patients of different Ethnicity origin. In the available literature, no previous research has focused on breast cancer-associated variants among the Khakass people (the indigenous people of the Russian Federation)., Methods: Twenty-six Khakass breast cancer patients were enrolled in the study. Genomic DNA was isolated from blood samples and used to prepare libraries using a Hereditary Cancer Solution kit. Next-generation sequencing (NGS) was performed using the MiSeq System (Illumina, USA)., Results: In our study, 12% of patients (3/26) carried a single pathogenic variant; 54% of patients (14/26) carried variants of uncertain significance (VUS) or conflicting variants; and 35% of patients (9/26) did not carry any clinically significant variants. Germline pathogenic variant in the ATM gene (rs780619951, NC&#95;000011.10:g.108259022C > T) was identified in two unrelated patients with a family history of cancer (7.6%, 2/26). The pathogenic truncating variant in the ATM gene (p. R805* or c.2413C > T) leads to the nonfunctional version of the protein. This variant has been earlier reported in individuals with a family history of breast cancer., Conclusions: Our pilot study describes the germline variant in the ATM gene associated with breast cancer in Khakass women of North Asia., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To present treatment outcomes in elderly and senile patients with cicatricial tracheal stenosis (CTS) and features of their perioperative management., Material and Methods: The study included 46 elderly and senile patients with CTS. We analyzed their gender and age, body mass index, etiology, extent and degree of stenosis, comorbidity index and ASA grade, postoperative complications according to TMM grading system., Results: Age of patients varied from 61 to 95 years (mean 66.38±8.65). Post-intubation stenosis was detected in 7 (15.2%) patients, post-tracheostomy CTS - in 39 (84.8%) patients (2 (4.3%) ones with tracheoesophageal fistula and 18 (39.1%) ones with tracheomalacia). CTS length ranged from 8 to 65 mm. The causes of invasive mechanical ventilation were traumatic brain and spinal trauma in 6 cases, emergency surgery in 11 cases and therapeutic diseases in 29 cases. CTS of cervical trachea was found in 21 patients, subglottic larynx and cervical trachea - 8 patients, cervical and upper thoracic trachea - 12 patients, thoracic segment - 3 patients, multifocal lesions - 2 patients. The Charlson index ranged from 5 to 12 points. ASA grade II was observed in 8 (17.4%) patients, III - 28 (60.9%), IV - in other ones. Circular resection was performed in 5 patients, laryngotracheoplasty - in 37 patients. CTS repair and tracheoesophageal fistula closure with laryngotracheoplasty were carried out in 2 patients. Postoperative complications occurred in 18 (39.1%) patients, mortality was 2.17%. In 21.7% of cases, complications were associated with tracheal suture. Endoscopic procedures, cryosurgery and hyperbaric oxygenation were used for correction. Good and satisfactory treatment outcomes were achieved in 86.5% of patients., Conclusion: Surgical treatment of CTS in elderly and senile patients requires participation of interdisciplinary team with special experience. Laryngotracheoplasty is safe and effective in these patients, and indications for circular resection are still limited.

Objective: To study the immediate results of angio- and bronchoplastic lobectomies for non-small cell lung carcinoma (NSCLC) in patients over 70 years old., Material and Methods: Thirty-one extended angio- and/or bronchoplastic lobectomies were performed in patients with NSCLC over 70 years old between January 2015 and December 2020. Mean age of patients was 74.5 ± 3.2 years. NSCLC stage IA was found in 5 (16.1%) cases, IB - 11 (35.5%), IIA - 12 (38.7%), IIB - 3 (9.7%) patients. Squamous cell carcinoma was diagnosed in 19 (61.3%) patients, adenocarcinoma - in other ones ( n =12). All patients had concomitant diseases with predominance of cardiorespiratory pathology. Severity of postoperative complications was assessed according to the Clavien - Dindo grading system., Results: Mean Charlson index was 5.34 ± 1.46 scores. ASA grade III was observed in 21 patients, grade IV - in 10 patients. Postoperative complications occurred in 12 (38.7%) patients, mortality rate was 6.4%. Prolonged air discharge through pleural drainage tubes (12.9%) and paroxysms of atrial fibrillation (16.1%) were the most common complications. Cardiac arrhythmia is a serious and fatal complication., Conclusion: Anatomical lung resections for NSCLC in patients over 70 years old have certain features of surgical technique and postoperative management. Prevention and prediction of postoperative complications along with rational perioperative management are of priority importance for increasing the safety of these interventions. Angio- and/or bronchoplastic lobectomy should be considered as the only surgical option characterized by high quality and satisfactory immediate results. This procedure is an adequate alternative to pneumonectomy.

Objective: To present the results of reconstruction of post-resection chest wall defects with nickel-titanium (TiNi) implants in patients with invasive NSCLC and to analyze the features of perioperative management., Material and Methods: We enrolled 9 patients with NSCLC involving the ribs after lobectomy or pneumonectomy with chest wall reconstruction. Defects were closed used TiNi mesh and rib prostheses. We selected the shape and dimensions of artificial ribs individually before surgery according to CT data and 3D models of reinforcing elements., Results: There were male smokers aged 64.6±4.6 years among patients (range 58-73). T3N0M0 was diagnosed in 6 patients, T3N1M0 - 2, T3N2M0 - 1. Squamous cell carcinoma was verified in 4 (44.4%) patients, adenocarcinoma - in 5 (55.6%) patients. All patients had comorbidities. Mean Charlson's comorbidity index was 6.56±4.6. Dimension of chest wall defect varied from 78 to 100 cm 2 . Postoperative period was uneventful without signs of respiratory failure. There were no lethal outcomes. Complications occurred in 33.3% of patients (prolonged air discharge through the drains, pleuritis and atrial fibrillation)., Conclusion: Surgical treatment of NSCLC spreading to the chest wall is a complex task requiring further improvement. Bioadaptive TiNi implants are a promising reinforcing material that allows successful reconstruction of post-resection chest wall defects with good anatomical, functional and cosmetic results. «Sandwich» technology is advisable for extensive defects. This approach includes 2 layers of knitted mesh and rib prostheses between these layers.

Objective: Despite the full range of anti-epidemic measures, the rapidly mutating SARS-CoV-2 continues to spread worldwide, causing respiratory and pulmonary pathologies. So far, there are no generally accepted clinical guidelines for treating post-resuscitation cicatricial tracheal stenosis (CTS) after COVID-19 associated pneumonia. This study sought to evaluate the clinical outcomes of surgical treatment and perioperative management of patients who developed CTS., Methods: A cohort of eleven working-age patients (eight women and three men) with CTS were treated surgically after undergoing invasive artificial ventilation ranging from 5 to 130 days. Along with scarring changes in the tracheal wall, tracheomalacia was noted in five (55.6%) individuals. Circumferential tracheal resection (CTR) with subsequent anastomosis, tracheolaryngeal reconstruction, and endoscopic methods were modalities used to restore airway patency. In cases of CTR combined with tracheoesophageal fistula (TEF), CTR was performed with dissection of the pathological stoma., Results: In 80% of the cases, CTS was located at the larynx and cervical trachea level. All patients managed to restore adequate breathing through their natural airways with preserved vocal function. No lethal outcomes were observed in the post-op period. Patient outcomes after CTR were considered excellent in nine patients who continued an active lifestyle and went straight to work. One patient, after laryngotracheoplasty and tracheal stenting, is at the final stage of treatment., Conclusions: These patients are at high risk of developing CTS and require dynamic monitoring. CTR allows early rehabilitation of patients with the best functional outcome. If CTR is contraindicated, laryngotracheoplasty also allows adequate debridement of the tracheobronchial tree and respiratory support., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Diagnosis of diaphragmatic injury is difficult in some cases. Symptoms of chronic posttraumatic diaphragmatic hernia are very diverse and associated with dysfunctions of the displaced abdominal organs and compression of thoracic organs. Previous blunt or open chest and abdominal trauma, as well as visible scars as a result of injury should be considered. Treatment concept assumes surgical correction of posttraumatic diaphragmatic hernia. Choice of surgical approach and type of intervention are determined individually. Despite the global trend towards minimally invasive endoscopic surgery, there are few reports on thoracoscopic correction of posttraumatic phrenic hernia. The authors report a rare case of thoracoscopic correction of posttraumatic diaphragmatic hernia in an 81-year-old man in 62 years after abdominal injury. Assuming degenerative changes in tissues and risk of defect enlargement following suture eruption, we used titanium nickelide reinforcing protectors. Video-assisted double port thoracoscopic access allowed minimally traumatic and successful correction of diaphragmatic hernia, that ensured early medical and social rehabilitation of the patient.

The report presents a case of non-standard two-stage treatment of post-traumatic multifocal cicatricial tracheal stenosis with atresia of subglottic larynx, involvement of vocal cords, and 33-year cannulation. At the first stage, bougienage through a tracheostomy, endoscopic argon plasma exposure, circular tracheoglottic resection with tracheostomy and 3 / 4 circle anastomosis, formation of a laryngotracheostomy with endoprosthetics were applied simultaneously. The second step was to eliminate the extensive fenestrated tracheo-laryngeal defect using titanium nickelide reinforcing implants. The individual algorithm made it possible to successfully eliminate complex tracheo-laryngeal stenosis with long-term cannulation and demonstrate excellent long-term treatment results.

Objective: To analyze postoperative outcomes and perioperative management of patients with post-intensive care tracheal stenosis and previous COVID-19 pneumonia., Material and Methods: There were 8 patients with post-intensive care tracheal stenosis and previous COVID-19 pneumonia aged 34-61 years between January 2021 and April 2021. Lung damage CT-3 was observed in 2 (25%) patients, CT-4 - in 5 (62.5%) patients. In one case, COVID-19 pneumonia with lung damage CT-2 joined to acute cerebrovascular accident. Post-tracheostomy stenosis was detected in 7 (87.5%) cases, post-intubation stenosis - in 1 patient. Duration of invasive mechanical ventilation ranged from 5 to 130 days. In 75% of cases, tracheal stenosis was localized in the larynx and cervical trachea. Two patients admitted with tracheostomy. In one case, an extended tracheal stenosis was combined with atresia of infraglottic part of the larynx. One patient had tracheal stenosis combined with tracheoesophageal fistula (TEF). Length of tracheal stenosis was 15-45 mm. Tracheomalacia was observed in 4 (50%) patients. All patients had severe concomitant diseases., Results: To restore airway patency, we used circular tracheal resection with anastomosis, laryngotracheoplasty and endoscopic methods. Tracheal resection combined with TEF required circular tracheal resection with disconnection of fistula. Adequate breathing through the natural airways was restored in all patients. There was no postoperative mortality. Three patients with baseline tracheal stenosis had favorable postoperative outcomes after circular tracheal resection. Four patients are at the final stage of treatment after laryngotracheoplasty and tracheal stenting., Conclusion: Patients after invasive mechanical ventilation for COVID-19 pneumonia are at high risk of cicatricial tracheal stenosis and require follow-up. Circular tracheal resection ensures early rehabilitation and favorable functional results. Laryngotracheoplasty is preferred if circular tracheal resection is impossible. This procedure ensures adequate debridement of tracheobronchial tree and respiratory support. Endoscopic measures are an alternative for open surgery, especially for intrathoracic tracheal stenosis and intractable tracheobronchitis.

Objective: To describe 10-year experience of treating the cicatricial tracheal stenosis (CTS) in a regional multi-field hospital., Material and Methods: There were 120 CTS patients aged 13-75 years. In 8 (6.7%) patients, CTS was combined with tracheoesophageal fistula (TPF). Post-intubation stenosis was diagnosed in 16 (13.3%) cases, post-tracheostomy - in 102 (85%) ones, post-traumatic - in 2 (1.7%) patients. CTS length ranged from 1.2 to 8 cm. Fifty (41.7%) patients had cervical CTS, 40 (33.3%) patients - cervico-thoracic tracheal stenosis, 11 (9.2%) patients - tracheal stenosis at the thoracic level. Nineteen (15.8%) patients had multifocal stenoses. We used endoscopic techniques, circular tracheal resection (CTR) and laryngotracheal reconstruction., Results: Postoperative mortality rate was 0.83%. CTR was performed in 33 patients, laryngotracheal reconstruction - 77, endoscopic stenting - 6 patients. In 4 cases, local CTS was eliminated by bougienage and argon plasma exposure. CTS was successfully disconnected with TEF using CRT in 3 cases, laryngotracheoplasty and stenting - in 5 cases. The fenestrated tracheal defect was closed by a three-layer autologous flap in 59 patients. Of these, autologous flap was reinforced with porous nickel-titanium implants in 17 patients. Postoperative complications after CRT occurred in 6 (16.7%) patients (anastomotic leakage - 2, anastomositis - 1, restenosis - 2). No patients died. Postoperative complications after laryngotracheal reconstruction were observed in 18 (23.4%) patients including 5 ones with restenosis who underwent CTR with a favorable outcome., Conclusion: CTS treatment requires a multidisciplinary approach. Each surgery has certain indications and place in treatment algorithm. CTR is highly effective, but may be accompanied by complications associated with tracheal anastomosis. Decrease of postoperative morbidity will improve immediate and long-term results of CTS treatment. The chosen treatment algorithm ensured good and satisfactory results in 98% of patients.

A case of the successful reconstruction of an extensive chest wall defect combined with a ventral hernia in a patient after multimodality treatment of breast cancer complicated by sternal and costal osteomyelitis is presented. To recover the chest mechanics, with emphasis on the supporting function, and to repair the hernial defect, customized reinforced "sandwich" TiNi rib endografts and knitted TiNi surgical mesh were used. A five-year follow-up indicated no recurrence of osteomyelitis or ventral hernia, and no failure/migration of the implants or instability of the thorax. Excellent clinical and functional outcomes were achieved pursuant to the Enneking score., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

In this study, we assessed the outcomes after surgical treatment of thoracic post-excision defects in 15 patients, using TiNi knitted surgical meshes and customized artificial TiNi-based ribs., Methods: Eight patients were diagnosed with advanced non-small cell lung cancer (NSCLC) invading the chest wall, of which five patients were T 3 N 0 M 0 , two were T 3 N 1 M 0 , and one was T 3 N 2 M 0 . Squamous cell carcinoma was identified in three of these patients and adenocarcinoma in five. In two cases, chest wall resection and repair were performed for metastases of kidney cancer after radical nephrectomy. Three-dimensional CT reconstruction and X-ray scans were used to plan the surgery and customize the reinforcing TiNi-based implants. All patients received TiNi-based devices and were prospectively followed for a few years., Results: So far, there have been no lethal outcomes, and all implanted devices were consistent in follow-up examinations. Immediate complications were noted in three cases (ejection of air through the pleural drains, paroxysm of atrial fibrillation, and pleuritis), which were conservatively managed. In the long term, no complications, aftereffects, or instability of the thoracic cage were observed., Conclusion: TiNi-based devices used for extensive thoracic lesion repair in this context are promising and reliable biomaterials that demonstrate good functional, clinical, and cosmetic outcomes.

Intermetallic porous SHS-TiNi alloys exhibit tangled and specific stress-strain characteristics. This article aims to evaluate the findings emanating from experiments using standard and proprietary instruments. Fatigue testing under repeated complex loading was used to measure the total number of load cycles before failure of the SHS-TiNi samples occurred. Of the tested samples, seventy percent passed through 10 6 cycles without failure due to the reversible martensite transformation in the TiNi phase, one of the prevailing constituents of a multiphase matrix. The fractured surfaces were analyzed using scanning electron microscopy and confocal laser scanning instruments. Microscopy studies showed that the entire surface of the sample is concealed by miscellaneous strata that result from the SHS processand effectively protect the porous alloy in a corrosive environment. Numerous non-metallic inclusions, which are also attributed to the SHS reaction, do not have a significant impact on the deformation behavior and fatigue performance. In this context, the successful in vivo functioning of porous grafts assessed in a canine rib-plasty model allows the bone substitute to be congruentially deformed in the body without rejection or degradation; it thus has a long operational life, often greater than 17 ×10 6 (22 × 60 × 24 × 540) cycles. It acknowledges the potential benefits of SHS-TiNi as a superior osteoplastic material and its high resistance to corrosion fatigue.

Objective: To evaluate the features of preoperative preparation and postoperative outcomes in patients with lung cancer and previous COVID-19 pneumonia., Material and Methods: There were 7 patients with non-small cell lung cancer and previous bilateral viral pneumonia between June 2020 and January 2021. In 3 cases, lung cancer was detected in a hospital for COVID-19 patients. Four patients had persistent structural changes in X-ray images. After appropriate preparation, all patients underwent total resection., Results: At admission, all patients had severe physical and functional exhaustion associated with prolonged hypoxia and adynamia that required preoperative rehabilitation. Considering high risk of thromboembolic complications, we administered anticoagulation throughout the entire perioperative period and after discharge. Surgical treatment included anatomical resection (extended lobectomy). Postoperative complications occurred in 2 cases and were associated with prolonged air discharge through the pleural drainage tube., Conclusion: As we study the consequences of the new coronavirus infection COVID-19, it becomes obvious that a new category of patients requiring specific diagnosis and treatment has emerged.

Objective: To study the immediate results of surgical treatment of advanced age patients with non-small cell lung cancer (NSCLC)., Material and Methods: We included 190 elderly and senile patients with NSCLC who underwent surgery at the thoracic department of the Tomsk Regional Clinical Hospital in 2010-2018. There were 149 men and 41 women. Cancer stage I was observed in 67 (35%) cases, stage II - 49 (26%) patients, stage III - 69 (37%) patients, stage IV - 5 (2%) patients. Squamous cell cancer was diagnosed in 94 patients, adenocarcinoma - 78 patients, large cell lung cancer - 18 patients. Paraneoplastic inflammatory complications occurred in 26% of patients, concomitant diseases - in 99% of patients. The research included anatomic lung resection with systematic mediastinal lymph node dissection and the absence of tumor at the resection line. There were 118 lobectomies and 47 pneumonectomies. In 74 cases, combined procedures were carried out. Lobectomy with pulmonary artery resection was performed in 18 patients, lobectomy with bronchial resection - in 10 cases. Twenty-five patients underwent video-assisted lobectomy., Conclusion: An acceptable morbidity and mortality allow you to expand the indications for radical surgery in geriatric patients with NSCLC. However, we must establish strict indications for pneumonectomy. Bronchial and angioplastic lobectomy may be an alternative to pneumonectomy in NSCLC patients.