Prophylaxis of complications in operations for cancer of middle and lower thirds of the esophagus

Objective. Improvement of the surgical treatment results in esophageal cancer. Маterials and methods. Results of surgical treatment of 43 patients, having cancer of middle and lower thirds of the esophagus, were analyzed. Lewis operation was performed in 38 patients, and Garlock operation – in 5. Circular suture stapler with second row of a П-like manual sutures was applied in 28 patients. In 15 patients anastomosis was formatted, using hand-sewn two-row suture. The method of anastomosing choice had depended upon local and general factors: the tumor localization, the esophageal wall changes in anastomotic site, degree of the water-electrolyte disorders, the protein balance, concurrent pathology. Prophylaxis of postoperative morbidity consisted of preoperative correction of laboratory indices, treatment of concurrent pathology, choice of the anastomosis formation method, postoperative intensive therapy. Results. Postoperative complications had occurred in 1 (2.3%) patient. Mostly frequent postoperative complication after resection for esophageal cancer constitute insufficiency of esophago-gastric anastomosis, which occurs under impact of general and local factors. General factors: disorders of the blood circulation, caused by cardiac insufficiency, hypoxia due to pulmonary insufficiency, coagulopathy, disorders of the protein and water-electrolyte metabolism. Reduction of influence of general factors on the postoperative morbidity occurrence was achieved using the intensive preoperative preparation conduction. Conclusion. The postoperative morbidity prevention turns effective while its accomplishment on all stages of treatment: during preoperative preparation, intraoperatively and postoperatively.

Effects of Late Surfactant Treatment Delivered After a Recruitment Maneuver on Respiratory Outcomes in Extremely Low Gestational Age Newborns: A Randomized Controlled Pilot Trial – LATE-REC-SURF Trial.

Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

Analysis of lethal cases of pneumonia caused by SARS-CoV-2 virus according to the data of pathology department of Kharkiv Regional Clinical Hospital for the first half of 2021

Background. Given the great medical, social and economic significance of clinical research, pathogenesis and epidemiology of coronavirus infection, it is important to study the epidemiological and pathomorphological features of this infection in Ukraine, especially in fatal cases of this disease. Objective: to analyze the lethal cases of pneumonia caused by SARS-CoV-2 in comparison with lethal cases of pneumonia of other etiologies according to the pathology department of Kharkiv Regional Clinical Hospital for the first half of 2021. Methods. The material of this study was the observation of an autopsy from the archival material the pathology department of Kharkiv Regional Clinical Hospital. The study of autopsy protocols took into account the seasonality of the disease, sex and age of the deceased, the number of bed-days, data of clinical diagnosis and coincidences of pathological diagnosis, as well as the ICD code. 256 protocols of pathological examinations for the first half of 2021 were studied. Results. Of the 256 deaths from pneumonia of various etiologies, 201 (78.52%) were caused by SARS-CoV-2 infection. The highest number of deaths from pneumonia was registered in March, April and May 2021. The number of deaths of patients aged 18-44 years was 4.3% of the total, 45-59 years – 13.28%, 60-74 years – 47.27%, 75-90 years – 35.16%. The study sample among patients died of pneumonia caused by SARS-CoV-2 was dominated by women (57.42%, 147 cases), the number of men was 42.58% (109 cases). The direct causes of death were pulmonary-heart failure, multiple organ failure, acute pulmonary insufficiency, chronic pulmonary insufficiency, and pulmonary embolism. Conclusion. The obtained data can be useful for the analysis of regional features of epidemiology and pathogenesis of coronavirus disease in eastern Ukraine.

Acid Sphingomyelinase Deficiency: A Clinical and Immunological Perspective

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease caused by deficient activity of acid sphingomyelinase (ASM) enzyme, leading to the accumulation of varying degrees of sphingomyelin. Lipid storage leads to foam cell infiltration in tissues, and clinical features including hepatosplenomegaly, pulmonary insufficiency and in some cases central nervous system involvement. ASM enzyme replacement therapy is currently in clinical trial being the first treatment addressing the underlying pathology of the disease. Therefore, presently, it is critical to better comprehend ASMD to improve its diagnose and monitoring. Lung disease, including recurrent pulmonary infections, are common in ASMD patients. Along with lung disease, several immune system alterations have been described both in patients and in ASMD animal models, thus highlighting the role of ASM enzyme in the immune system. In this review, we summarized the pivotal roles of ASM in several immune system cells namely on macrophages, Natural Killer (NK) cells, NKT cells, B cells and T cells. In addition, an overview of diagnose, monitoring and treatment of ASMD is provided highlighting the new enzyme replacement therapy available.

Does Preoperative Halo-Gravity Traction Reduce the Degree of Deformity and Improve Pulmonary Function in Severe Scoliosis Patients With Pulmonary Insufficiency? A Systematic Review and Meta-Analysis

Background: Halo-gravity traction is a commonly used clinical intervention to reduce surgical risk in patients with scoliosis before surgical correction. Some previous studies have focused on the application of halo-gravity traction on patients with severe spinal deformity and pulmonary insufficiency, but the overall effect of halo-gravity traction has not been fully understood. The object of the present study was to perform a meta-analysis exploring the efficacy of preoperative halo-gravity traction on radiographic measurement and pulmonary function in severe scoliosis patients with pulmonary insufficiency.Methods: We searched the medical works of literature completed before January 17, 2021, in the databases of Pubmed, Embase, and Cochrane Library. Studies that quantitatively analyzed the effects of halo-gravity traction on the deformity and pulmonary functions of patients with severe scoliosis were included. Two researchers independently conducted the literature search, data extraction, and quality assessment. We used the Review Manager Software (version 5.4) for statistical analysis and data analysis. Mean difference (MD) with 95% confidence intervals (CIs) were calculated to evaluate the effects of halo-gravity traction.Results: Seven studies involving 189 patients received halo-gravity traction therapy preoperatively were analyzed in our study. Preoperative halo-gravity traction significantly ameliorated the degree of deformity in severe scoliosis patients with pulmonary insufficiency, especially reduced coronal Cobb angle and sagittal Cobb angle effectively [mean deviation (MD) = 2 7.28 (95%CI 21.16–33.4), p &lt; 0.001; MD = 22.02 (95%CI 16.8–27.23), p &lt; 0.001]. Preoperative halo-gravity traction also improved the pulmonary functions in patients, especially increasing %FVC and %FEV1 [MD = −0.0662 (95%CI −0.0672–−0.0652), p &lt; 0.001; MD = −0.0824 (95%CI −0.0832–−0.081), p &lt; 0.001].Conclusions: Preoperative halo-gravity traction for severe scoliosis patients shows significant improvement in the degree of deformity and pulmonary functions. Halo-gravity traction is an effective method to improve the tolerance of patients to surgery in the perioperative period.

The Role of GM-CSF Autoantibodies in Infection and Autoimmune Pulmonary Alveolar Proteinosis: A Concise Review

Autoantibodies to multiple cytokines have been identified and some, including antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), have been associated with increased susceptibility to infection. High levels of GM-CSF autoantibodies that neutralize signaling cause autoimmune pulmonary alveolar proteinosis (aPAP), an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency. Defective GM-CSF signaling leads to functional deficits in multiple cell types, including macrophages and neutrophils, with impaired phagocytosis and host immune responses against pulmonary and systemic infections. In this article, we review the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis along with the increased incidence of infections (particularly opportunistic infections). Therefore, recombinant human GM-CSF products may have potential for treatment of aPAP and possibly other infectious and pulmonary diseases due to its pleotropic immunomodulatory actions.

Congenital isolated absence of a single cusp of pulmonary valve

A 25-year-old, previously asymptomatic female, presented to the outpatient clinic with episodic palpitations for past 6 months. She was acyanotic and showed no peripheral stigmata of infective endocarditis. Transthoracic echocardiography revealed dilated right ventricle with severe low-pressure pulmonary regurgitation. A cardiac computed tomography angiography performed for evaluation of pulmonary arterial circulation and intracardiac anatomy revealed isolated absence of posterior pulmonary cusp. The two other (right anterior and left anterior) cusps were normal and covered only part of the valve orifice, resulting in pulmonary insufficiency. The main pulmonary artery showed asymmetric dilatation. No other structural heart defects were noted.

Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite

Tissue fibrosis causes debilitating human diseases such as liver cirrhosis, heart failure, chronic kidney disease and pulmonary insufficiency. It is a dynamic process orchestrated by specific subsets of monocyte-macrophages, fibroblasts, pericytes and hepatic stellate cells. Fibrosis is linked to tissue inflammation. Pro-inflammatory macrophages promote fibrosis by driving myofibroblast differentiation and macrophage myofibroblast transition. Myofibroblasts express α-smooth muscle cell actin (α-SMA) and secrete extracellular matrix (ECM) proteins notably collagen I and III. Deposition of ECM proteins at injury sites and interstitial tissues distorts normal structure and impairs vital functions. Despite advances in the mechanisms of fibrosis at cellular, molecular and genetic levels, prevention and treatment of fibrotic diseases remain poorly developed. Recent reports suggest that 5-methoxytryptophan (5-MTP) is effective in attenuating injury-induced liver, kidney, cardiac and pulmonary fibrosis. It inhibits macrophage activation and blocks fibroblast differentiation to myofibroblasts. Furthermore, it inhibits hepatic stellate cell differentiation into myofibroblasts. As 5-MTP is an endogenous molecule derived from tryptophan catabolism via tryptophan hydroxylase pathway, it is well-suited as a lead compound for developing new anti-fibrotic drugs. This article provides an overview of 5-MTP synthesis, and a critical review of its anti-fibrotic activities. Its mechanisms of actions and potential therapeutic value will be discussed.

18β-Glycyrrhetinic Acid Protectes Neonatal Rats with Hyperoxia Exposure Through Inhibiting ROS/NF-κB/NLRP3 Inflammasome

Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Oxygen supplementation is a lifesaving therapeutic measure used for premature infants with pulmonary insufficiency. However, oxygen toxicity is a significant trigger for BPD, and oxidative stress-induced inflammatory responses, in turn, worsens the oxidative toxicity resulting in lung injury and arresting of lung development. Glycyrrhiza radix is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of Glycyrrhiza radix, has a powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has protective effects on neonatal rats with hyperoxia exposure. Newborn Sprague-Dawley rats were kept in either 21% (normoxia) or 80% O2 (hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weights and alveolar development, and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia exposure increased ROS level and pulmonary inflammation, and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment decreased ROS level, inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA protects neonatal rats with hyperoxia exposure through inhibiting ROS/NF-κB/NLRP3 inflammasome.

Halo-gravity traction in the treatment of complex spinal deformities in children with respiratory dysfunctions

HGT is a safe technique as the world literature describes complications in the form of loosening of the pins or superficial infections of the skin around the pins, which are not significant and do not pose a threat to the patient’s life. Purpose – to improve the results of the ventilation function of the lungs in patients with complex spinal deformities through the preliminary use of halo gravity traction and to introduce an effective and safe method for the treatment of complex spinal deformities in children with respiratory dysfunctions. Materials and methods. 64 children with complex spinal deformities (>100°) were treated in the orthopedic and traumatology department of the Okhmatdet NSPU using halo gravity traction during the period from 2003 until 2018. Of these, 38 are boys and 26 are girls. The average age of the patients was 11.6 years. The average Risser score was 3.8 (P>0.01). Results. According to the data of spirography performed, 46% of patients had moderate ventilation disorders and 54% – severe ventilation disorders (FVC<60% – grade 3 and 4 of ventilation failure). Mixed type disorders were recorded in 83% of patients, and restrictive type disorders in 17% (8/48) of children. After HGT, there was an improvement in pulmonary function indicators: an increase in FVC from 63.19% to 71.77% and FEV1 from 54.71% to 65.46%, Tiffeneau-Pinelli index – from 74.59% to 85.33%. Compared with the initial level of indicators, the improvement in FVC was 13.6% after HGT and 14.6% in dynamics during the year, and FEV1 – 19.6% and 21.6%, respectively. The results obtained indicate a significant improvement in the ventilation function of the lungs, especially due to the degree of FEV1 increase, which correlates with the degree of improvement in performance, mortality and life prognosis. Conclusions. The use of HGT makes it possible to improve the results of the final correction of spinal deformity, which in turn significantly improves the ventilation function of the lungs, which in turn helps to reduce the risks of mortality due to pulmonary insufficiency in adulthood. The choice of the appropriate methods of surgical correction for complex deformity of the spine is a prerequisite for successful treatment and the achievement of three-dimensional correction of the spine to maximally approximate its parameters to the physiological norm. The indication for halo gravity traction is a rigid scoliotic deformity of the spine with a deformity angle (>100°). This study was conducted in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institutions mentioned in the work. Informed parental agreement was obtained for the research. No conflict of interests was declared by the authors. Key words: spinal deformity, respiratory dysfunctions, halo-gravity traction.