Degree Of Respiratory Failure Research Articles

Classification of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare hereditary disease from the group of ciliopathies with extensive locus and allelic heterogeneity (ORPHA 244, 98861; OMIM 242650, 244000). This disease is inherited by autosomal dominant or autosomal recessive type and, less often, by X-linked type (OMIM 300424). Retinitis pigmentosa develops in the X-linked PCD variant. The overall minimum global prevalence of PCD according to European data is 1 : 7554. There is no generally accepted classification of PCD in the international classification of diseases (ICD), 10th revision. PCD is not presented in ICD-10 as a separate medical entity, and the code Q32.4 – Other congenital bronchial anomalies – is used for coding. In the new edition of ICD-11, the code LA75.Y is highlighted – Other specified structural abnormalities of the lungs.Primary ciliary dyskinesia. However, there is no generally accepted classification of PCD. The aim of the study was to develop a classification of primary ciliary dyskinesias to improve the efficiency of medical care for patients during follow-up.Methods. European and Russian clinical recommendations, as well as ICD 10th and 11th revision, Classification of Respiratory Insufficiency (2020), Order of 27.08.19 No.585n “On classifications and criteria used in the implementation of medical and social expert assessment of citizens by federal state institutions of medical and social expert assessment” (as amended on 06.10.21) were used to create the classification.Results. The classification of PCD was created and can be recommended for use in clinical practice. The classification was based on the presence or absence of the Sievert – Kartagener syndrome (complete, not complete), as well as clinical and instrumental characterization of bronchopulmonary changes based on the presence of chronic obstructive bronchitis, bronchiectasis (specifying the type and localization), pneumofibrosis with the process activity (exacerbation, remission), and the degree of respiratory failure. It is recommended to take into account extrapulmonary manifestations of PCD, such as rhinosinusitis, media otitis, congenital heart defect, and complications. It is recommended to use the PICADAR (PrImary CiliAry DyskinesiA Rule) score and to include the results of video microscopy, DNA diagnosis, and microbiological examination in the diagnosis.Conclusion. The application of the proposed classification can be useful in the dynamic observation of the patient, therapy and in the conduct of medical and social expert assessment.

ПРОГНОЗИРОВАНИЕ РИСКА НЕБЛАГОПРИЯТНОГО ИСХОДА СРЕДИ ПАЦИЕНТОВ С COVID-19, ГОСПИТАЛИЗИРОВАННЫХ В ИНФЕКЦИОННЫЙ ГОСПИТАЛЬ

Introduction. The identification of predictors of mortality in COVID-19 remains one of the primary directions among all studies devoted to this topic. The search and selection of the most sensitive prognostic tools is the basis for improving the prognosis in patients with COVID-19 and for the proper allocation of health resources. Aim. The aim is to develop a prognostic model for assessing the risk of an adverse outcome in the first two days in patients with COVID-19 hospitalized in an infectious diseases hospital. Material and Methods: the clinical and anamnestic data of 148 patients with an unfavorable (fatal) outcome in the first two days after hospitalization and 364 patients with a favorable outcome up to 10 bed days were analyzed. Statistical analysis was carried out using the StatTech v. 2.8.8 program (developed by Stattech OOO, Russia). Results and discussion. According to the results of our study, the following predictors were included in the prognostic model: age, male gender, degree of respiratory failure, type 2 diabetes mellitus, obesity, arterial hypertension and coronary heart disease. Under the influence of a set of predictors, the risk of an unfavorable outcome in patients with COVID-19 increased in male patients by 1.1 times, with an increase in age by 1 year by 1.1 times, in the presence of grade 2 respiratory failure by 5.9 times, grade 3 respiratory failure by 17.4 times, type 2 diabetes by 1.1 times, obesity by 1.4 times, arterial hypertension by 1.8 times, coronary heart disease by 3.7 times. Conclusion. The obtained prognostic model for assessing the risk of an adverse outcome in patients with COVID-19 has good prognostic abilities, its sensitivity and specificity were 76.5% and 77.8%, respectively. The resulting model can help optimize the prediction of outcome in hospitalized patients with COVID-19

Evaluation of the neutrophil-leukocyte index in patients with cardiac disorders and new coronavirus infection

Background: The neutrophil-leukocyte index (NLI) is an independent predictor of an unfavorable outcome in stable ischemic heart disease, as well as of mortality in patients with acute coronary syndromes and uncontrolled heart failure. A number of studies have shown the informative value of NLI for the prediction of severe course of COVID-19. NLI variability in COVID-19 with comorbid baseline physical diseases and cardiovascular disorders in particular, has not been studied.
 Aim: To evaluate the clinical value of NLI in hospitalized patients with COVID-19 depending on their concomitant cardiac disorders.
 Materials and methods: In this retrospective quantitative study we have analyzed the data from medical files of the patients with the diagnosis of new coronavirus infection confirmed by polymerase chain reaction, treated in a specialized in-patient department of infectious diseases in 2020 to 2022. Previously diagnosed cardiac disorders were defined as any past history of these disorders. The results of instrumental and laboratory work-up were assessed before treatment.
 Results: The analysis included 226 patients with median age of 50.0 (Q1Q3: 42.063.0) years, with 81.4% (n = 184) of them being men. Ninety four (41.6%) patients had no previously diagnosed cardiovascular disorders. Arterial hypertension by the time of admittance was present in 132 (58.4%), ischemic heart disease, in 77 (34.1%), atherosclerotic and/or post-infarct cardiosclerosis, in 82 (36.3%), and chronic heart failure, in 77 (34.1%) of the patients.
 In the total study group (n = 226) the median NLI was 2.6 (1.574.47). The larger was the volume of the lung involvement (assessed by computed tomography at admittance), the higher was NLI (p = 0.009, Kruskal-Wallis test). There was an association between the NLI value and the degree of respiratory failure (p 0.001, Kruskal-Wallis test). Median NLI in the patients with cardiac disorders (irrespective of their nosology) was significantly higher than that in the patients without any history of cardiovascular problems: 3.30 (2.095.42) versus 1.95 (1.423.62) (p 0.001, Mann-Whitney U-test). We found significant difference in the NLI values for each type of cardiac disorders, compared to that in the patients without history of cardiovascular disorders, including for the patients with arterial hypertension (p 0.001, Kruskal-Wallis test), ischemic heart disease (p 0.001, Mann-Whitney U-test), atherosclerotic cardiosclerosis (p = 0.001, Mann-Whitney U-test), and chronic heart failure (p = 0.040, Kruskal-Wallis test).
 Conclusion: We have confirmed the contribution of cardiovascular disorders to the course of COVID-19 and the clinical value of NLI as a convenient laboratory marker of the severity of infectious disease.

Results of endoscopic hemostasis methods in treatment of gastrointestinal bleeding in patients with SARS-CoV-2

The development of gastrointestinal bleeding from erosive and ulcerative defects of the mucous membranes of the upper gastrointestinal tract, which, according to the world literature, occurs in 2–13 % of hospitalized patients with COVID-19, is a multifaceted problem that is still relevant, but has not been adequately reflected in scientific publications. The aim of the work was to study the clinical characteristics of patients with gastrointestinal bleeding on the background of SARS-CoV-2 and evaluate the methods of endoscopic hemostasis. The article analyzed cases of bleeding from the upper gastrointestinal tract in 115 patients suffering from the novel coronavirus infection. The severity of the course of COVID-19 was assessed according to the criteria of the NEWS scale, the degree of respiratory failure, and radiological data. 114 out of 115 patients had comorbidities; the most common diseases were cardiovascular diseases, endocrine pathology, chronic kidney disease, and oncopathology. The most common sources of bleeding (82 %) were acute or chronic ulcers of the stomach and/or duodenum against the background of erosive hemorrhagic lesions of the mucosa. The following methods of endoscopic hemostasis were used: endoscopic clipping, endoscopic injections, applications of hemostatic agents and solutions, and combined methods which were used more often. Hemostasis was achieved in all cases. Repeated bleeding occurred in 22 cases (19.1 %) with subsequent achievement of endo-hemostasis. Mortality was 66.95 % (77 patients), with such causes of adverse outcomes as increasing multiple organ failure, respiratory distress syndrome, and septic shock.

Body mass index as a predictor of the severity of coronavirus infection in patients with cardiovascular pathology

Aim. To investigate the association between body mass index (BMI) and the severity of COVID-19, respiratory failure, and fatal outcome in patients with cardiovascular disease.Materials and Methods. The study included 283 patients with confirmed COVID-19. COVID-19 severity was determined according to the Russian National Guidelines for the Prevention, Diagnostics, and Treatment of COVID-19. The degree of respiratory failure was defined according to the oxygen saturation. BMI was determined by the Quetelet's index, whereas overweight and obesity were diagnosed in accordance with the World Health Organization classification.Results. Comparison of BMI in patients with mild, moderate, and severe COVID-19 did not show statistically signifi differences, although patients with overweight and obesity had a higher frequency of respiratory failure. Further, grade 3 (severe) respiratory failure had average BMI of 28.7 kg/m2 (men) and 34.2 kg/m2 (women), while those with grade 1 (mild) respiratory failure had average BMI of 26.1 kg/m2 (men) and 31.2 kg/m2 (women). In keeping with these fi patients with a fatal outcome had higher BMI than those with a favorable outcome (31.1 kg/m2 and 27.2 kg/m2, respectively). After an adjustment for the chronic heart failure, BMI between the patients with a fatal and favourable outcome remained different (28.4 kg/m2 and 26.3 kg/m2, respectively). Logistic regression analysis showed that BMI itself had low prognostic signifi yet is became higher if combined with a COVID-19 severity and degree of respiratory failure.Conclusion. Patients with a high BMI are more likely to have a severe respiratory failure and fatal outcome. Therefore, this parameter can be used as an additional factor for the risk stratification.

Model for predicting the risk of severe bronchial asthma in children

Objective: to develop a model for predicting the severe course of bronchial asthma (BA) in children.
 Materials and methods: a comprehensive examination was conducted of 213 children aged 3 to 12 years suffering from atopic asthma (mild course was observed in 85.0%, moderate — in 10.3%, severe — 4.7%). A statistical analysis of clinical and laboratory parameters was performed using the logistic regression method, which allowed us to identify a number of factors that increase the probability of developing a more severe course of BA in children.
 Results. A mathematical model for predicting the risk of severe bronchial asthma in children has been developed, including such factors as the child's age, the degree of respiratory failure, the value of the peak expiratory rate, the duration of the disease, and the presence of an association of exacerbations of the disease with changes in the weather and physical activity. A computer program has also been developed that allows you to automatically calculate the amount of risk after entering the child's data.
 Conclusion. The use of this model makes it possible to predict the further course of BA with a high degree of confidence, and, consequently, to correct the basic therapy in time to prevent the development of complications in a sick child.

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.

Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair machinery. Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1). Gene expression related to DNA repair was investigated in two independent cohorts of hospitalized Covid-19 patients (Cohort 1; 15 patents and 5 controls, Cohort 2; 15 patients and 6 controls), and by publicly available datasets. Patients and healthy controls showed comparable amounts of oxidative DNA damage as assessed by 8-oxoG while levels of several BER proteins were increased in Covid-19 patients, indicating enhanced DNA repair in acute Covid-19 disease. Furthermore, gene expression analysis demonstrated regulation of genes involved in BER and double strand break repair (DSBR) in PBMC of Covid-19 patients and expression level of several DSBR genes correlated with the degree of respiratory failure. Finally, by re-analyzing publicly available data, we found that the pathway Hallmark DNA repair was significantly more regulated in circulating immune cells during Covid-19compared to influenza virus infection, bacterial pneumonia or acute respiratory infection due to seasonal coronavirus. Although beneficial by protecting against DNA damage, long-term activation of the DNA repair machinery could also contribute to persistent inflammation, potentially through mechanisms such as the induction of cellular senescence. However, further studies that also include measurements of additional markers of DNA damage are required to determine the role and precise molecular mechanisms for DNA repair in SARS-CoV-2 infection.

Serum neuromodulin content in preterm infants with perinatal lesions of the central nervous system in the first day of life

Presently, authors of scientific publications pay much attention to the study of individual neuromarkers of damage to the central nervous system in newborns. One such marker is the growth protein neuromodulin.The aim of the study is to estimate the concentration of neuromodulin in the first day of life in preterm infants with perinatal damage to the central nervous system and compare it with the clinical indicators of newborns in the early neonatal period.Characteristics of children and research methods. 81 extremely preterm newborns were examined, which were divided into groups depending on the presence of intraventricular hemorrhages: Group 1 — 48 preterm infants in whom intraventricular hemorrhage was verified during the observation in the early neonatal period; Group 2 — 33 preterm infants without intraventricular hemorrhage. Determination of the concentration of the GAP-43 protein in the blood serum was carried out by enzyme immunoassay. The groups were comparable in terms of weight and height parameters, gestational age, the degree of respiratory failure at birth, and the need for mechanical ventilation (p<0,05).Results. Group 1 had a significantly lower Apgar score at the end of the 1st (p=0,034) and 5th minutes of life (p=0,037) compared to Group 2. A comparative analysis of the concentration of neuromodulin revealed that in preterm infants of Group 1, the values of neuromodulin were significantly higher than in preterm infants of Group 2 (1,469 [1,284; 1;966] and 0,541 [0,461; 0,595] ng/mL, respectively; p<0,001). The degree of intraventricular hemorrhage (r=0,771; p<0,001), the minimum amplitude of the amplitude-integrated electroencephalography (r=–0,404, p=0,004), the Ballard score (r=–0,614, p=0,019) were statistically significantly correlated with serum neuromodulin concentration.Conclusions. Characteristics of the concentration of GAP-43 in preterm infants with perinatal lesions of the central nervous system are given depending on the presence of intraventricular hemorrhage and the gestational age on the first day of life, significant correlations between clinical data and the level of the studied protein are revealed.

Ischemic stroke in the debut of coronavirus infection

Introduction. The risk of ischemic stroke (IS) on the background of COVID-19 is about 5% and is associated with a more severe course of coronavirus infection (CVI).The aim of the study was to identify risk factors and clinical features of IS in a debut of CVI in neurological inpatients.Materials and methods. A prospective analysis of the neurological status, clinical, biochemical parameters, ultrasound examination of brachiocephalic vessels, computed tomography (CT) of the brain and the lungs was performed in 15 patients in the acute period of IS with a later detected PCR SARS-Cov-2.Results. The average age of patients is 70.3±7 years. Risk factors for IS in the debut of CVI: stenosis of 30-50% of the internal carotid artery (ICA), arterial hypertension in 100%; dyslipidemia in 86.7%; type 2 diabetes mellitus in 46.7%; coronary heart disease in a third of cases. Lung damage according to CT did not exceed 50%. There is no clear correlation between IS severity, its localization and degree of respiratory failure. The localization of IS corresponded to the side of ICA stenosis. The young patient had signs of antiphospholipid syndrome, extravasal compression of both vertebral arteries, hypoplasia of the posterior connective artery corresponding to the focus of extensive infarction in the middle cerebral artery basin.Discussion. A feature of the debut of CVI in the acute period of IS was the absence of subfebrility in the presence of increased CRP, thrombocytopenia, hyperfibrinogenemia, and a more than 3-fold increase in D-dimer, indicating early activation of platelet-vascular hemostas. The fact of the development of IS according to the side of the stenotic vessel is explained by the manifestation of latent organic pathology under the influence of CVI, thanks to the affinity of SARS-CoV-2 for the ACE2 receptors present in the vascular endothelium.Conclusion. In connection with the present epidemiological situation, the fact of the onset of IS in CVI without hyperthermia suggests an early PCR test with subsequent adequate treatment of CVI in a specialized institution together with neurologists.

Comment on “Usefulness of lung ultrasound in the early identification of severe COVID-19: results from a prospective study”

To EditorWe have read this article with great interest, where a pattern of correlation is established between lung ultrasound findings and the degree of respiratory failure and prognosis in patients with Coronavirus disease 2019. However, we think that some aspects of this study can be better analyzed.

ВЗАИМОДЕЙСТВИЕ ВИРУСА SARS-COV-2 И СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ: КЛИНИЧЕСКАЯ ХАРАКТЕРИСТИКА И ПАТОГЕНЕТИЧЕСКОЕ ОБОСНОВАНИЕ

Introduction. The coronavirus disease 2019 (COеVID-19) caused by the SARS-CoV-2 virus led to the global pandemic, and by the beginning of August 2021, more than six million people fell ill in Russia. The study of the interaction between the SARS-CoV-2 virus and the cardiovascular system has great importance for the effective treatment of patients with this disease. Aim. The aim of the study was to identify the frequency of cardiovascular complications, based on the analysis of the patient’s medical histories with viral pneumonia caused by SARS-CoV-2 virus. And to compare the results obtained with the data of literary sources and justify their pathogenetic occurrence. Material and methods. 70 medical histories of patients with viral pneumonia caused by the SARS-CoV-2 virus who were admitted to the temporary infectious diseases hospital in Kazan were analyzed. The comorbidity, routine methods of laboratory (Complete blood count, qualitative and quantitative troponin test), and instrumental (ECG, Echo) diagnostics were studied. Descriptive statistics were calculated: median and interquartile range, categorical variables were presented in quantity and percentage. An unpaired t-test was used for the analysis of statistical significance. The critical value was assumed to be p≤0.05. Literature in eLIBRARY.ru, PubMed, GoogleScholar, Web of Science in recent years, mainly in 2020-2021, were analyzed. Results and discussion. Among the comorbidity: hypertension – in 31 (44%) patients, chronic heart failure – in 14 (20%) patients, coronary heart disease – in 10 (14.2%), diabetes mellitus – in 8 (11.4%), and 16 (22%) patients suffered from obesity. The most frequent complications were regurgitation on the valves (57,14%), cardiac arrhythmias (35,7%), of which supraventricular arrhythmias were the most common. There was no dependence of the increased level of Tr I on the degree of respiratory failure. Among patients with elevated Tr I levels, a chronological association with a previous infection with specific symptoms was revealed in all patients with high reliability of the presence of myocarditis in 12 (17,14%) patients. Conclusion. COVID-19 affects not only the respiratory system but also has a significant impact on the cardiovascular system because of the patient's immune response and the probable cytopathic effect of the virus. Key words: coronavirus, COVID-19, SARS-CoV-2, myocarditis, arrhythmia, angiotensin.

The lineage of coronavirus SARS-CoV-2 of Russian origin: Genetic characteristics and correlations with clinical parameters and severity of coronavirus infection

The identification of new SARS-CoV-2 and human protein and gene targets, which may be markers of the severity and outcome of the disease, are extremely important during the COVID-19 pandemic. The goal of this study was to carry out genetic analysis of SARS-CoV-2 RNA samples to elucidate correlations of genetic parameters (SNPs) with clinical data and severity of COVID-19 infection.Material and Methods. The study included viral RNA samples isolated from 56 patients with COVID-19 infection who received treatment at the City Hospital No. 40 of St. Petersburg from 04/18/2020 to 04/18/2021. Patients underwent physical examination with the assessments of hemodynamic and respiratory parameters, clinical risk according to National Early Warning Score (NEWS), computed tomography (CT) of the chest, and laboratory studies including clinical blood analysis, assessment of ferritin, C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, creatinine, and glucose levels. All patients tested positive for SARS-CoV-2 RNA by polymerase chain reaction (PCR). Single nucleotide polymorphisms (SNPs) in viral RNA were identified through the creation of cDNA libraries by targeted sequencing (MiSeq Illumina). Bioinformatic analysis of viral samples was performed using the viralrecon v2 pipeline with the further annotation via Pangolin and Nextlade. Sampled genomes were visualized using the Integrative Genomics Viewer (IGV) software. Statistical data processing (descriptive statistics and graphical analysis of data relationships from diff erent tables) was performed using a GraphPad device on the Prism 8.01 platform.Results. A comparative analysis of SNP frequencies in the virus genome in samples from deceased and discharged patients was carried out. The SNPs associated with risk of death (OR > 1), neutral SNPs (OR = 1), and protective SNPs (OR < 1) were identifi ed. Patient samples were infected with 14 lines of SARS-CoV-2, fi ve of which (B.1.1.129, B.1.1.407, B.1.1.373, B.1.1.397, and B.1.1.152) were of Russian origin. The SNPs in the samples infected with the strains of non-Russian origin were associated with an increased risk of mortality (OR = 2.267, 95% confi dence interval 0.1594-8.653) compared to the SNPs in the samples obtained from the group of patients infected with the strains of Russian origin. Positive correlations were identifi ed between the average SNP number, nonsynonymous SNPs, and S-protein SNPs with the degree of respiratory failure, total NEWS score, CT-based form of disease, duration of treatment with mechanical ventilation, disease outcome, levels of LDH, glucose, D-dimer, and ferritin, and RNA amount in the PCR test. S-protein SNPs negatively correlated with the leukocyte and neutrophil counts.

Tocilizumab in patients with COVID-19: which patient, time, and dose?

Tocilizumab (TCZ) is a recombinant anti-interleukin-6 monoclonal antibody which showed uprising evidence as an anti-inflammatory agent which modulates the cytokine storm in patients with COVID-19. However, proper use of the drug requires selection of the appropriate patient and timing. The two main factors which might improve patient selection are the degree of respiratory failure and systemic inflammation. TCZ can decrease the mortality and progression to invasive mechanical ventilation in patients with severe COVID-19 who are not yet invasively ventilated. However, its use in invasively ventilated patients did not yet gain the same level of evidence especially when administered after > 1 day from mechanical ventilation. Being an anti-inflammatory and immunomodulatory drug, TCZ was mostly used in patients with COVID-19 who have clear signs of cytokine storm. However, the drug still showed positive response in some studies which did not strictly select patients with elevated markers of systemic inflammation. Thus, it is warranted to investigate and/or re-analyze the role of the drug in patients with severe COVID-19 and with no signs of systemic inflammation. TCZ is used in a dose of 8 mg/kg which can be repeated if there was no clinical improvement. However, there are no clear criteria for judgment of the success of the first dose. Being a drug with a major effect on gross outcomes in a serious pandemic with millions of mortalities, TCZ should be meticulously investigated to reach definitive indications and number of doses to avoid drug overuse, shortage, and side effects.

Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial.

New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). 23 hospitals in Norway. Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n= 42), HCQ (n= 52), or standard of care (SoC) (n= 87). In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. The trial had no placebo group. Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. National Clinical Therapy Research in the Specialist Health Services, Norway.

The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns

Background: The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. β_C is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. β_IT is a physiological, truncated isoform of β_C and is known to act as physiological inhibitor of β_C. Objective: The aim of this study was to determine the ratio of β_IT and β_C in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. Methods: We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). β_IT and β_C expression were determined in peripheral blood cells by real-time PCR. β_IT expression, defined as the ratio of β_IT and β_C, was correlated with the respiratory score. Results: β_IT expression was found in all 59 recruited newborns with a trend toward higher β_IT in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; p = 0.066). Seriously ill newborns (score 3) had significantly higher β_IT than healthy newborns ([score 0], p = 0.010). Healthy preterm infants had significantly higher β_IT expression than healthy term infants (p = 0.019). Conclusions: β_IT is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that β_IT may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of β_C and, therefore, maintaining surfactant in respiratory ill newborns.

Evaluation of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 Patients: Results from the NOR-Solidarity Randomised Trial

Background: There is an urgent need for new treatment modalities in COVID-19 patients. Recently, the WHO Solidarity trial showed no effects of remdesivir or hydroxychloroquine (HCQ) on mortality. However, the antiviral effects of these drugs and the possible relation to clinical characteristics at admission is not known.Methods: NOR-Solidarity is an independent add-on study to the WHO Solidarity trial, including biobanking, and a clinical three-month follow-up. Eligible patients were adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection. Patients were randomly assigned to receive remdesivir, HCQ or standard of care (SoC). In-hospital mortality, admission to intensive care unit and initiation of mechanical ventilation were primary and secondary clinical endpoints shared with WHO Solidarity. Secondary endpoints were impact of remdesivir or HCQ on SARS-CoV-2 clearance in the oropharynx, as well as their effects on systemic inflammation and the degree of respiratory failure (ClinicalTrials.gov: NCT04321616).Findings: Between March 28 and October 4, 185 patients from 23 hospitals in Norway were randomized and 181 included in the full analysis set: remdesivir (n=42), HCQ (n=52) and SoC (n=87). No significant differences in mortality during hospitalisation, ICU admission or occurrence of mechanical ventilation between the treatment groups and SoC were observed. There was a marked decrease in SARS-CoV-2 load in oropharynx during the first week with similar decrease and 10-day levels between remdesivir, HCQ and their respective SoC. Remdesivir and HCQ did not exert any effect on the degree of respiratory failure or on inflammatory parameters in peripheral blood. Notably, the lack of anti-viral effect was not associated with symptom duration, level of viral load or presence of antibodies against SARS-CoV-2 at hospital admittance.Interpretation: We found no effect on viral clearance by either remdesivir or HCQ in hospitalised COVID-19 patients.Trial Registration: (ClinicalTrials.gov: NCT04321616)Funding: National Clinical Therapy Research in the Specialist Health Services, Norway.Declaration of Interests: All authors declare no competing interest.Ethics Approval Statement: The trial protocol was approved by the Regional Ethic Committee (118684) and by the Norwegian Medicines Agency (20/04950-23) and was overseen by an independent data and safety monitoring board.

PROGNOSTIC VALUE OF SERUM MAGNESIUM LEVEL AS A MARKER OF ENDOTHELIAL DYSFUNCTION IN PREMATURE BIRTH NEONATES

Optimal magnesium supply during pregnancy and overcoming magnesium deficiency is essential due to its physiological role in many metabolic processes. Metabolic transformations with magnesium are necessary for the vitamin D activation, energy supply for homocysteine restoration, and regulation of nitric oxide synthesis. Magnesium deficiency increases the risk of premature birth, and the diffusion of magnesium to the fetus increases precisely from the second trimester of pregnancy, therefore, its deficiency can adversely affect neonatal adaptation. The aim of this work was to investigate the relationship between the serum magnesium level and markers of endothelial dysfunction and the clinical features of the early neonatal period course. Results. The average level of serum magnesium in 58 premature birth neonates was 1.21 ± 1.09 mg/dl on the first day. A borderline low level of serum magnesium (less than 1.2 mg/dl) was found in 72.41% of the examined children. Statistical analysis did not reveal a relationship between the serum magnesium level on the first day after birth and the studied markers of endothelial dysfunction (eNOS gene variants, nitric oxide level). A positive correlation was found between serum magnesium level and Apgar scores in newborns. For nitric oxide, a negative correlation with the Apgar 2 score and a positive correlation with the degree of respiratory failure were found. Serum magnesium and nitric oxide levels in premature birth neonates measured on the first day after birth enable to assess the course of the antenatal period and to predict postpartum adaptation.

Immunohistochemical evaluation of surfactant-associated protein in fibrosis-cavernous pulmonary tuberculosis

Background. Despite the progress and development of scientific directions in various fields of medicine, the problem of tuberculosis and its morphological manifestations remains relevant and is not fully disclosed due to complex pathogenesis, the presence of various clinical forms, therapeutic pathomorphosis, torpid to therapy, the presence of relapses. It is known that a surfactant system occupies a special place in the system of local lung protection.Aim. To study the condition of surfactant-assotiated protein A in the foci of specific destruction and in the surrounding intact lung tissue to assess its functional status, degree of respiratory failure and possible dissemination of tuberculous inflammation.Material and Metods. An analysis of 163 lung fragments of the dead or operated on for cavernous pulmonary tuberculosis with active bacterial excretion of 89 fragments and with clinical abacilation – 74 was carried out. Results A morphological study revealed stereotypical dynamic depression of surfactant-associated protein A in all the samples studied, both in the areas of cavernous destruction and pericavernouse zone, and in intact lung tissue. The maximum intensivity of the immunohistochemical expression of this surfactant protein was recorded in the alveolar macrophages, which indicated intensive recycling and utilization of the components of the surfactant.Conclusion. Minimizing the production of surfactant components and its active utilization in intact lung tissue leads to a collapse of the alveoli with subsequent progression of respiratory failure.

Нарушение кровообращения в легких и развитие хронической дыхательной недостаточности у пациентов с обычной интерстициальной пневмонией

Purpose: To determine the features of circulatory disorders in the lungs in patients with ordinary interstitial pneumonia (OIP) at different stages of the pathological process and with the development of comorbid conditions. 
 Material and methods: The analysis of the results of radiation research methods: computer tomography, computed angiography and single photon emission computed tomography in 64 patients with common interstitial pneumonia. The selection criteria were the presence of respiratory failure and pulmonary hypertension.
 Results: The combination of interstitial and alveolar changes, their distribution in the lower parts of both lungs with subpleural localization are mainly pathognomonic for IPI. In 85 % of patients with OIP and the formation of a “cellular lung”, local perfusion disorders of various forms, of small size, subsegmental level, located symmetrically in the diaphragm regions were determined. The main distinctive CT signs of adherence to vascular pathology: pulmonary pattern mosaic; subpleural infiltration sites of the lung tissue of heterogeneous structure; defects in filling the pulmonary artery with a contrast agent during CT angiography; triangular subpleurally located areas of perfusion disturbance on SPECT (when SPECT/CT is combined), localized in the area of lung infarction, or in the zone of no changes on CT.
 Conclusion: The development of pulmonary hypertension and chronic respiratory failure in OIP is determined by several factors that have an active or passive effect on pulmonary hemodynamics. Worsening of the patient’s condition and an increase in the degree of respiratory failure and pulmonary hypertension, contributes to complication of the pulmonary vascular system – pulmonary thromboembolism and (or) thrombosis in situ, as well as persistent infectious inflammatory processes. In the presence of irreversible morphological changes in the lung parenchyma therapeutic measures do not affect the state of microcirculation in the lungs.

Diaphragm ultrasonography in amyotrophic lateral sclerosis: a diagnostic tool to assess ventilatory dysfunction and disease severity.

Respiratory failure represents an unavoidable step in patients with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND). The development of diaphragm ultrasonography (DUS) provides an alternative useful and risk-free tool to supply clinical, functional, and neurophysiological assessment of respiratory muscle weakness. Our aim was to evaluate if sonographic changes (thickness and echogenicity in the costal portion of the diaphragm, at rest and during respiratory movements) may be used in ALS patients to assess disease severity over time, to rule out any risk or discomfort due to traditional neurophysiological investigations. Twenty ALS patients (mean age, 64.6 ± 10.5years) were enrolled and data were compared with age-matched healthy volunteers; DUS data were correlated with respiratory function and disease severity scale. Examinations were performed using Telemed Echo-wave II or Esaote MyLabGamma devices in conventional B-Mode. Mean resting thickness was reduced in all cases; changes in thickness during inspiration and expiration were also reduced (p < 0.0001) and lost in severe cases (n = 3). In bulbar-onset disease, respiratory scores were strictly correlated with the difference in diaphragm thickness between full inspiration-and expiration-as well as on the diaphragm thickness in expiration (p < 0.001). DUS represents a simple, painless, and risk-free tool; moreover, it provides useful functional and structural insights to the understanding of diaphragm function and the degree of respiratory failure in ALS.