CLINICAL STUDIES
Aim of the study. To study the effect of helium-oxygen mixture on predictors of postoperative pulmonary complications in cancer patients with chronic obstructive pulmonary disease (COPD).
Materials and methods. A single-center prospective clinical study with historical control included 208 patients, among them 104 patients received helium-oxygen mixture inhalations (70% helium and 30% oxygen) in the preoperative period (He group) and 104 patients were the historical control group (Ctrl group). Given the risk of bias associated with confounders, we conducted a one-to-one matching analysis based on pseudorandomization to adjust for the unbalanced baseline characteristics of the groups. We used logistic regression to develop the pseudo-randomization estimates. We used the nearest neighbor matching 1:1 with a caliper of 0.1 to achieve better similarity among matched pairs. After pseudo-randomization, we included 87 patients in each group, ensuring adequate balance across all covariates. A multivariate logistic regression analysis was performed to identify factors associated with the risk of postoperative pulmonary complications.
Results. In the He group, there was a statistically significant improvement in a number of functional parameters compared to the Ctrl group. FEV1, FVC, mod. Tiffno index values in the He group increased significantly (р = 0,0009; р = 0,0115; р = 014, respectively), gas exchange parameters (PaO₂, PaCO₂, pH, SpO₂) improved (р = 0.0006; р = 0.004; р = 0.0097; р = 0.001, respectively). Hypoxia tolerance tests also showed significantly greater values in the He group (Stange test, р = 0.016; Sabrazes (Gench) post-exhalation breath-holding test, р = 0.024). Analysis of postoperative parameters showed significant advantage of the He group over the control group in terms of critically important clinical outcomes. At the final stage of stepwise selection, three independent predictors were included in the risk model for postoperative pulmonary complications: SpO₂, the breath-holding test, and the duration of postoperative mechanical ventilation. The quality of the model was high, with a correctly classified case rate of 92.2%, a Hosmer–Lemeshow goodness-of-fit statistic of р = 0.933, and a total model significance of p<0.000.
Conclusion. We performed the first clinical study that showed the importance of preoperative preparation using a helium-oxygen mixture in cancer patients with chronic obstructive pulmonary disease and identified predictors of pulmonary complications after thoracic surgery.
Necrotizing pulmonary infections (NPI) emerge as severe complications of community-acquired pneumonia (CAP), and immune system cells are involved in their pathogenesis. Highly informative biomarkers are required to determine high-risk patients to prevent life-threatening complications of NPI. Previously, we have shown that variations in immune cell numbers can be employed as prognostic biomarkers in NPI. We proposed that genetic variants encoding receptors detected on the surface of neutrophils, monocytes, and macrophages migrating to lung tissues during inflammation may predict the unfavorable course of NPI. One of these candidate genes could be the OLR1 gene, which encodes LOX-1 receptors that bind oxidized low-density lipoproteins oxLDL on the surface of immune and other cells.
The aim of the study. To find out the OLR1 gene single nucleotide polymorphism contribution to the clinical course of NPIs (pleural empyema) and variability in the number of immune cells in patients with post-CAP NPI.
Materials and methods. The study included patients of the Moscow City Hospital (aged 18–87 years, n = 216) with NPIs developed after CAP. Categorical data were described by indicating absolute values, which were compared using four-field contingency tables and the χ² test with Yates' correction for sample continuity and Fisher's exact test (FET).
Results. NPIs were the most common complication of CAP. In patients with NPI and the minor allele G OLR1 rs11053646, which encodes the LOX-1 167N variant, the course of the disease was less likely to be complicated by a fistula (p = 0.0015; exact Fisher test (EFT); OR = 3.55, 95% CI: 1.55–8.13; RR = 2.37, 95% CI: 1.24–4.50; n = 216). However, the significance of this association was influenced by previous COVID-19 documented in patient's medical history based on PCR test results. For patients who had been infected with COVID-19, this association persisted (p = 0.0058; EFT; OR = 7.27, 95% CI: 1.54–34.3; RR = 4.28, 95% CI:1.31–16.23; n = 81), whereas in patients with no PCR test confirmed COVID-19, this association was not statistically significant (p = 0.1065, EFT, n = 135). Thus, only post-COVID-10 carriers of the minor allele G OLR1 rs11053646 were protected from a severe course of NPIs complicated with fistula development. A study in a limited subgroup of patients showed a trend for a fistula development to associate with increased OxLDL plasma concentration of more than 100 ng/ml (p = 0.045; n = 19).
Conclusion. Post-COVID-19 сarriers of major OLR1 rs11053646 CC genotype exhibit increased risk for the unfavorable course of NPI (pleural empyema) complicated with fistula. The presence of alternative G allele of OLR1 rs11053646 in patient genotype associates with favorable course of NPIs.
EXPERIMENTAL STUDIES
Cardiac arrest remains one of the leading causes of death worldwide. Even with successful resuscitation, patient outcomes are often poor due to post-resuscitation syndrome, which includes cerebral hypoxia, myocardial dysfunction, microcirculatory disorders, coagulation abnormalities, and systemic inflammation. Argon, an inert noble gas, has neuroprotective and cardioprotective properties, making it a promising candidate for early post-resuscitation therapy.
The aim of the study was to evaluate the organoprotective properties of an argon-oxygen mixture when inhaled in the early post-resuscitation period for 2 hours after asphyxial circulatory arrest in rats.
Materials and methods. A prospective randomized controlled experimental study was conducted on male Wistar rats (n = 43) using an asphyxial circulatory arrest model. The animals were divided into three groups: sham-operated (SO, n = 12), circulatory arrest with resuscitation (CAR, n = 13), and circulatory arrest with resuscitation and two-hour inhalation of a 70%/30% argon-oxygen mixture in the post-resuscitation period (CAR + iAr, n = 18). Hemodynamics, microcirculation, blood gas composition, coagulation (low-frequency piezothromboelastography), neurological status, and biomarkers of organ damage were evaluated. Beclin-1 and caspase-3 expression was analyzed immunohistochemically.
Results. Argon inhalation did not have a significant effect on systemic hemodynamics, but it was accompanied by improved tissue oxygenation and metabolism: a decrease in blood lactate (p = 0.043), an increase in the p/F oxygenation index (p = 0.001), and stabilization of microcirculation variability (Kv, σ). Statistically significantly increased expression of the Beclin-1 protein in the lungs, myocardium, and hippocampus reflected activation of autophagy. In the CAR + iAr group, there was an improvement in neurological status compared to CAR (p = 0.02), a decrease in serum neuron-specific enolase (p = 0.011), and a decrease in the number of caspase-3-positive cells (p = 0.011), indicating a reduction in apoptosis and damage to the nervous tissue. Argon had a moderate anticoagulant and antiplatelet effect (coagulation drive intensity — CDI, and maximum clot firmness-MCF reduction), while maintaining normal processes of clot retraction and lysis. The electrophysiological parameters of the heart (QRS, QTc) varied within the physiological range, indicating the absence of pro-arrhythmic effects in argon.
Conclusion. Early inhalation of argon-oxygen mixture after circulatory arrest has a multisystem protective effect: improves oxygenation and microcirculation, promotes activation of autophagy mechanisms in vital organs, reduces the severity of neuronal damage, and modulates blood clotting in some measure. Argon can be considered a promising therapeutic agent for post-resuscitation syndrome. Further clarification is needed to assess argon’s molecular mechanisms of action and long-term outcomes after its use.
FOR PRACTIONER
The aim of the study. To compare the effectiveness of thrombolytic therapy in patients with ischemic stroke with forteplase and alteplase in clinical practice.
Materials and methods. A single-center retrospective cohort study was conducted using data from the reperfusion interventions registry at the Arkhangelsk regional vascular center. The primary endpoint was patients’ functional recovery at discharge from the hospital. The incidence of type 2 intracranial hemorrhages according to the Heidelberg bleeding classification, mortality, and the duration of hospital stay were analyzed as the secondary endpoints. Descriptive statistics were used. Simple and multivariate multiple linear and logistic regression models were constructed to assess the relationship of forteplase use with functional recovery and length of hospital stay.
Results. The study involved 213 patients with the mean age of 68 (60; 76) years, including 111 (52.1%) men. Forteplase was used in 91 (42.7%) patients. Modified Rankin scale scores of 0–2 were documented in 52 (57.14%) and 51 (41.8%) patients in the forteplase and alteplase groups, respectively, p = 0.019. After correction for potential confounders, no relationship was found between achieving good functional recovery and the use of forteplase: adjusted odds ratio was 1.04 [95% CI 0.54–2.01], p = 0.91. The incidence of type 2 parenchymal hemorrhages was 3.3% in the forteplase group vs 0.8% in the alteplase group, p = 0.315, and the mortality rates were 6.59% vs 11.48%, respectively, p = 0.247. The use of forteplase did not affect the length of hospital stay in a multivariate analysis: B = –0.54 [95% CI –3.74–2.66], p = 0.741.
Conclusion. Thrombolysis with forteplase is an effective and safe method of treatment in the acute period of ischemic stroke. Rates of achieving good functional recovery, incidence of intracranial hemorrhage, and length of hospital stay were comparable in groups treated with forteplase and alteplase after correction for significant confounders.
Bronchial asthma remains one of the most common chronic respiratory diseases characterized by episodes of severe airway obstruction. In cases of refractory status asthmaticus complicated by critical hypercapnia and decompensated respiratory acidosis, conventional methods of respiratory support, including mechanical ventilation, are often insufficient. The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) is considered a promising method for stabilizing gas exchange and minimizing ventilator-induced damage.
Objective: to share clinical experience in successful use of VV-ECMO in patients with refractory status asthmaticus complicated by severe hypercapnia and decompensated respiratory acidosis, resistant to correction by conventional respiratory support and lung-protective ventilation.
Materials and methods. VV-ECMO was used as an extracorporeal alternative for lung gas exchange function in two female-patients with refractory status asthmaticus complicated by severe hypercapnia and decompensated respiratory acidosis.
Results. VV-ECMO reduced the risk of developing ventilator-induced lung injury (VILI) allowing maintenance of lung-protective mechanical ventilation, and therefore, enabling accelerated respiratory rehabilitation. In both presented cases, early initiation of VV-ECMO improved gas exchange parameters and mitigated ventilator-associated complications, thereby confirming the relevance of its’ use in patients with severe exacerbations of bronchial asthma complicated by uncontrolled hypercapnia.
Conclusion. Presented experience highlights the importance and feasibility of further VV-ECMO exploration as an intensified approach for management of severe BA exacerbations accompanied by critical hypercapnia and respiratory failure. This might require larger-scale randomized trials to identify optimal indications and protocols for VV-ECMO use.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a viable modality for supporting circulation in patients with severe ventricular arrhythmia and high risk of acute hemodynamic instability during radiofrequency ablation (RFA) procedure.
Objectives: (a) To demonstrate the feasibility and effectiveness of VA-ECMO as a mechanical circulatory support during radiofrequency ablation in patients with sustained-recurrent ventricular tachyarrhythmia, which allows to achieve control of arrhythmia and improves survival in this high-risk cohort; (b) to determine the patient-selection criteria for VA-ECMO.
Case reports. We analyzed 5 cases of sustained -recurrent ventricular tachycardia in patients (all men, mean age 59 years) who were hospitalized in the intensive care unit. All patients had multiple episodes of ventricular tachycardia despite continuous conservative therapy. Four patients underwent radiofrequency ablation of the arrhythmogenic substrate with VA-ECMO support, resulting in complete elimination of tachyarrhythmia. The patients were successfully weaned from ECMO and subsequently discharged. In the fifth patient with left ventricular ejection fraction of 17–20% due to dilated cardiomyopathy the invasive procedure was excluded due to the terminal stage of heart failure, extremely high perioperative risk, and anticipated RFA failure. After patient's condition stabilized, he was referred to a tertiary center for orthotopic heart transplantation (OHT).
Results. All patients who underwent ECMO-assisted RFA achieved complete control of arrhythmia without recurrence during the entire follow-up period. Successful weaning from ECMO and discharge from the hospital confirmed the effectiveness of this strategy. One case demonstrated the limitations of the method, i. e. in a patient with terminal myocardial damage RFA was considered palliative.
Conclusion. ECMO support during ablation procedure allows the use of RFA in patients with severe structural myocardial pathology and high risk of hemodynamic instability. Scrupulous selection of patients with localized arrhythmogenic substrate and the potential for restoring myocardial function after RFA are the key components for procedural success.
REVIEWS & SHORT COMMUNICATIONS
Objective. The aim of this review is to summarize the pathological mechanisms associated with the toxicity of phenothiazines in overdose.
Materials and methods. A database search was conducted on PubMed, Google Scholar and eLibrary were used to identify original research articles, clinical reports, review articles, editorials, commentaries, and brief communications. Additional sources not identified through the search of these databases were analyzed after reviewing the reference lists of the selected articles. Articles were selected based on the relevance of the title and abstract to the purpose of this review.
Results. This review analyzes the mechanisms of action of phenothiazines in the context of their long-term clinical use and in overdose, as well as the mechanisms of action of proposed potential areas of application of phenothiazines. Clinical manifestations of phenothiazine poisoning are predominantly characterized by antagonism of dopamine D₁–D₄ receptors, histamine H₁ receptors, α₁–α₂ α-adrenergic receptors and muscarinic acetylcholine receptors M₁–M₂. In addition, phenothiazines are able to increase the permeability of the blood-brain barrier through apoptosis, increase global methylation, effectively enhance chemotherapy of some tumors and provide neuroprotection by reducing GFAP production (PKC-δ/NOX/MnSOD pathway).
Conclusions. Given the potential for new applications of phenothiazines, further study of the effects of phenothiazines on the central nervous system in overdose, with a focus on repeat overdose episodes, is important at the morphological level to identify the underlying morphological substrate. Further study of the mechanisms associated with phenothiazine use is needed to develop more effective therapeutic strategies to improve patient outcome, not only in psychiatry but also in other disciplines.
ISSN 2411-7110 (Online)



































