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Диагностика синдрома поликистозных яичников (СПКЯ) в подростковом возрасте по-прежнему вызывает много вопросов. Проблема состоит в том, что характеристики нормального полового созревания часто совпадают с симптомами СПКЯ, поэтому ряд исследователей предлагают к постановке диагноза применять более жесткие требования. Мы с осторожностью подходим к постановке окончательного диагноза СПКЯ с учетом его трактовки как глобальной проблемы соматического здоровья — эндокринно-метаболического статуса, сердечно-сосудистого и онкогенного риска. Кроме того, одним из основных способов терапии СПКЯ является прием комбинированных оральных контрацептивов, которые нежелательно назначать девочкам-подросткам в случае олиго- и аменореи без тщательного обследования и использования всех возможностей витаминофитотерапии и гестагенов.

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

We herein report the first clinical case of prosthetic replacement of the ascending aorta and aortic arch to repair a giant aneurysm in a 7-month-old child. The ascending aorta and arch replacement to the level of left subclavian artery was performed using a no. 16 Polymaille prosthesis, the brachiocephalic trunk was reimplanted into the vascular prosthesis and the kinked section of the left common carotid artery was removed, followed by reimplanting the left common carotid artery into the left subclavian artery. First, proximal anastomosis with the vascular prosthesis was created using a no. 16 Polymaille prosthesis and the vascular suture was strengthened with a Teflon strip. During circulatory arrest, the aortic arch was crossed between the orifice of the left common carotid artery and left subclavian artery, with the cut extended to the isthmus region along the small curvature of the arch. The brachiocephalic trunk was aligned and brought down, with subsequent implantation into the ascending aorta prosthesis 2 cm below the initial fixation point. In the final stage, the kinked section of the left common carotid artery was resected and the aligned left carotid artery was directly reimplanted into the left subclavian artery using end-to-side anastomosis. The patient developed tracheobronchitis and moderate heart failure during the postoperative period. The duration of mechanical ventilation was 16 hours. Infusion and antibacterial therapy were discontinued on postoperative day 8. On postoperative day 13, the patient was discharged and referred to the outpatient centre for further treatment and rehabilitation. A sufficiently large-sized prosthesis allows for further development in paediatric patients. This is facilitated by the preservation of the native aortic root with restored valve function and the formation of a bevelled distal anastomosis with a small unchanged aortic section in the isthmus region, which maintains growth potential. This first reported case of an infant demonstrates the possibility of combination interventions on the aortic arch and brachiocephalic artery during the first year of life.Received 30 January 2021. Revised 24 March 2021. Accepted 29 March 2021.Funding: The study did not have sponsorship.Conflict of interest: The authors declare no conflicts of interests.Contribution of the authors: The authors contributed equally to this article.

Background Over 1 million Americans undergo joint replacement each year, and approximately 1 in 75 will incur a periprosthetic joint infection. Effective treatment necessitates pathogen identification, yet standard-of-care cultures fail to detect organisms in 10% to 20% of cases and require invasive sampling. We hypothesized that cell-free DNA (cfDNA) fragments from microorganisms in a periprosthetic joint infection can be found in the bloodstream and utilized to accurately identify pathogens via next-generation sequencing. Methods In this prospective observational study performed at a musculoskeletal specialty hospital in the U.S., we enrolled 53 adults with validated hip or knee periprosthetic joint infections. Participants had peripheral blood drawn immediately prior to surgical treatment. Microbial cfDNA from plasma was sequenced and aligned to a genome database with >1,000 microbial species. Intraoperative tissue and synovial fluid cultures were performed per the standard of care. The primary outcome was accuracy in organism identification with use of blood cfDNA sequencing, as measured by agreement with tissue-culture results. Results Intraoperative and preoperative joint cultures identified an organism in 46 (87%) of 53 patients. Microbial cfDNA sequencing identified the joint pathogen in 35 cases, including 4 of 7 culture-negative cases (57%). Thus, as an adjunct to cultures, cfDNA sequencing increased pathogen detection from 87% to 94%. The median time to species identification for cases with genus-only culture results was 3 days less than standard-of-care methods. Circulating cfDNA sequencing in 14 cases detected additional microorganisms not grown in cultures. At postoperative encounters, cfDNA sequencing demonstrated no detection or reduced levels of the infectious pathogen. Conclusions Microbial cfDNA from pathogens causing local periprosthetic joint infections can be detected in peripheral blood. These circulating biomarkers can be sequenced from noninvasive venipuncture, providing a novel source for joint pathogen identification. Further development as an adjunct to tissue cultures holds promise to increase the number of cases with accurate pathogen identification and improve time-to-speciation. This test may also offer a novel method to monitor infection clearance during the treatment period. Level of evidence Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The ongoing pandemic disaster of coronavirus erupted with the first confirmed cases in Wuhan, China, in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) novel coronavirus, the disease referred to as coronavirus disease 2019, or COVID-19. The World Health Organization (WHO) confirmed the outbreak and determined it a global pandemic. The current pandemic has infected nearly 300 million people and killed over 3 million. The current COVID-19 pandemic is smashing every public health barrier, guardrail, and safety measure in underdeveloped and the most developed countries alike, with peaks and troughs across time. Greatly impacted are those regions experiencing conflict and war. Morbidity and mortality increase logarithmically for those communities at risk and that lack the ability to promote basic preventative measures. States around the globe struggle to unify responses, make gains on preparedness levels, identify and symptomatically treat positive cases, and labs across the globe frantically rollout various vaccines and effective surveillance and therapeutic mechanisms. The incidence and prevalence of COVID-19 may continue to increase globally as no unified disaster response is manifested and disinformation spreads. During this failure in response, virus variants are erupting at a dizzying pace. Ungoverned spaces where nonstate actors predominate and active war zones may become the next epicenter for COVID-19 fatality rates. As the incidence rates continue to rise, hospitals in North America and Europe exceed surge capacity, and immunity post infection struggles to be adequately described. The global threat in previously high-quality, robust infrastructure health-care systems in the most developed economies are failing the challenge posed by COVID-19; how will less-developed economies and those health-care infrastructures that are destroyed by war and conflict fare until adequate vaccine penetrance in these communities or adequate treatment are established? Ukraine and other states in the Black Sea Region are under threat and are exposed to armed Russian aggression against territorial sovereignty daily. Ukraine, where Russia has been waging war since 2014, faces this specific dual threat: disaster response to violence and a deadly infectious disease. To best serve biosurveillance, aid in pandemic disaster response, and bolster health security in Europe, across the North Atlantic Treaty Alliance (NATO) and Black Sea regions, increased NATO integration, across Ukraine’s disaster response structures within the Ministries of Health, Defense, and Interior must be reinforced and expanded to mitigate the COVID-19 disaster.

Health-care-related infections are becoming more relevant today. The difficulty and largely of diagnosis increased impact of adverse effects (postoperative period, increase of bed-days, use of irrational antibacterial therapy, use of excessive methods of disinfection) factors of the hospital environment on the human body, contributing to the development of severe postoperative complications, among them, sternomediastinitis occupies a special place in cardiac surgery. The clinical case we represent clearly demonstrates the atypical flow of sternominetite caused by the hypervirulent strain Klebsiella pneumoniae blaNDM-Type. Generally, sternomediastinitis causes Staphylococcus epidermidis, Staphylococcus haemolyticus. Every week the patient stays in the cardiothoracic ward of the hospital is associated with a 15 % increase in the risk of mediastinitis development. The data indicate the need for continuous epidemiological monitoring of the relevant microorganisms that are potential agents of nosocomial infections. Thus, adequate diagnosis, choice of rational treatment tactics and effective antibacterial therapy significantly improve the prognosis of the current of a given severe disease. Early epidemiological diagnosis will help to reduce the risk of the development and spread of hospital-acquired infections in the post-operative period.

Aim: to assess an opportunity of using infrared thermometry in predicting obstetric perineal tear. Materials and Methods. There was conducted a prospective analysis of 40 childbirth cases recorded in 2019-2020. There were stratified 2 study groups: Group 1 included 30 women without perineal injuries; Group 2 - 10 women with obstetric perineal rupture. Infrared thermometry in the posterior perineal junction projection was performed during the second period of labor at two timepoints: 1 - onset of the second labor period; 2 - descent of fetal head parietal tubercles. Results. The temperature difference between the first and second timepoints in Group 1 was 1.8 [1.71; 1.99] °C, in Group 2 - 2.7 [2.42; 2.82] °C (U = 54.000, p = 0.002). The rate of perineal temperature decline > 2.0 °C in Group 1 was 20 % (6/30), in Group 2 - 80 % (8/10) of cases (х 2 = 11.868; p = 0.001). Such observation exhibited relatively high strength of relationship (V = 0.545). It is noteworthy that if perineal temperature decline at least by 2.0 °C for 2 minutes from descent of fetal head parietal tubercles to full birth of fetal head, the perineal rupture occurred in 100 % of cases (х 2 = 7.556; p = 0.006), also featured with relatively high strength (V = 0.435). Conclusion. Perineal skin temperature decline at least by 2.0 °C for 2 minutes or more from descent of fetal head parietal tubercles may potentially be used as a criterion justifying episiotomy.

The aim was to the assess the health impact of substances measured in the air originating from the decomposition of organic components of sewage sludge in the landfill. Methods: The study was performed at the Severny landfill in a suburb of Saint Petersburg. Sanitary and chemical methods of landfill emissions research we applied. Health risk assessment of the chemicals polluting the air was used. Results. In total, 30 pollutants are emitted from the landfill to the air with the total emission of 768.11 tons/year. The main pollutant was methane. The emissions contained 12 pollutants with a carcinogenic effect. A total of 18 substances comprised 99.9 % of the total index of non-carcinogenic hazard with dihydrosulfide (hydrogen sulfide), formaldehyde and ammonia being the main contributors. Conclusions. The maximum values of carcinogenic risk from exposure to formaldehyde at the calculated points reached 5.8x10-6. The levels of individual carcinogenic risk from formaldehyde exposure correspond to the second risk range (maximum permissible). The value of the total individual carcinogenic risk does not exceed the value of 7.4E-06. The maximum values of the hazard factors for chronic exposure are due to hydrogen sulfide - 0.27. The maximum values of the exposure hazard index at calculated points on the respiratory system are 0.46; on the immune system - 0.16; on the eyes - 0.15. These risk levels were rated as minimal.

The purpose of the research is to study the cumulative properties of the long-acting preparation "Flyblock insecticidal tag". Materials and methods. The cumulative properties of the "Flyblock insecticidal tag" preparation were studied by the subchronic toxicity method on 20 male guinea pigs, which were divided into experimental and control groups of 10 animals each. A solution for impregnating a polymer plate of the preparation "Flyblock insecticidal tag" was applied to the skin, on a previously trimmed area of the coat 4 × 4 cm in size in the spinal column using a disposable syringe for injection in doses from 0.1 to 1.12 LD50. To animals of the experimental group, the drug was applied at a dose of 187.40 mg/kg, equal to 1/10 of the previously established single lethal dose of LD50, then every subsequent 4 days the dose was increased 1.5 times. The control group of animals received 0.9 % saline solution at a dose of 2 ml. For 27 days, the physiological state of the animals, the nature and degree of activity and coordination of movements, the presence of tremors, seizures, paresis, paralysis were assessed; took into account the condition of the hair and mucous membranes, studied the symptoms of intoxication and recorded the death of animals. Dead guinea pigs were subjected to autopsy, detailed examination of the thoracic and abdominal cavities, and macroscopic examination of parenchymal organs and tissues. Results and discussion. When studying the cumulative properties of the preparation "Flyblock insecticidal tag", the value of the cumulation coefficient was set equal to 11.6. In accordance with the classification of chemicals, including pesticides, a prolonged-release drug belongs to the group of substances with a weakly expressed degree of cumulation.

Purpose. Analysis of intraocular pressure after cataract phacoemulsification with IOL implantation in patients with cataract in combination with primary angle-closure glaucoma. Material and methods. The dynamics of IOP after phacoemulsification with IOL implantation was studied in 46 patients (58 eyes) with cataract in combination with angle-closure glaucoma. The initial stage of glaucoma was diagnosed in 5.17%; developed-in 70.69%; distant-in 24.14%. Intraocular pressure was normal at 77.59%, moderately elevated at 12.07%, and high at 10.34% in the hypotensive mode. Follow-up period was from 1 month to 2.5 year s. Results. Depending on the postoperative ophthalmotonus, patients were divided into three groups: IOP is equal to the preoperative level, IOP is lower than the preoperative indicators, and IOP is higher than the initial one. The level of ophthalmotonus corresponded to the preoperative level in most eyes during the entire follow-up period, and by the age of 2.5, the number of these patients reached 71.43%. The number of patients with intraocular pressure is lower than preoperative values (3–9 mm Hg) was 62.74% in the first months, and by the end of the observation period it decreased to 19.04%. Intraocular pressure higher than preoperative pressure (2–4 mm Hg) was registered in 20 eyes (34.48%). In one case, the increase in IOP did not exceed the statistical norm and did not require correction, in 14 eyes IOP was compensated by additional medication, and in 5 eyes with far-advanced glaucoma, surgery was required. Conclusion. After phacoemulsification of cataracts in closed-angle glaucoma, it is not always possible to obtain a sufficient and persistent hypotensive effect, which probably indicates that the iridocorneal angle of retention intraocular fluid in the outflow pathways is attached to the blockade, which requires further study.

An experimental model of an original device for the diagnosis of uterine scar integrity in the early postpartum period is described. The design of the device is described, along with methods of assessing uterine scar integrity in the early postpartum period; the effectiveness of using this device for the diagnosis of defects is assessed in an experimental model. The diagnostic accuracy of the device is compared with that of manual examination of the uterine cavity.

A clinical case of a complete fundal rupture of the uterus at the first stage of labor of a woman with a uterine scar from a previous cesarean section in the lower uterine segment is addressed in this article. During clinical observation, the patient did not have hemorrhagic and pain syndromes. Operative delivery was performed due to primary uterine inertia. A newborn did not show any signs of asphyxia. During the operation, a rounded defect of 4 5 cm in size, penetrating the uterine cavity, was detected in the uterine fundus. It was sutured with a triple-row suture. The area of the lower segment was thinned to 2 mm, with deformation and defects not detected. In the postpartum period, subinvolution of the uterus was noted. The patient was discharged from hospital in satisfactory condition on the 10th day of the postpartum period.

A clinical case of operative delivery of a woman with stage 3 genital prolapse, which was diagnosed at 3536 weeks of gestation, is addressed in this article. The woman became pregnant while using intrauterine device. During cesarean section, the patient was diagnosed with complete uterus didelphia. In the abdominal cavity, between the two uteruses, a T-shaped intrauterine device was detected, with no signs of uterus perforation revealed.

A disturbed uterine contraction activity is a basic stage in the pathogenesis that result in a pathological or abnormal labor. Now some new ways f uterine activity were discovered that may be helpful to find promising targets for future medications. This article presents a clinical case of pregnancy with an abnormal labor and describes diagnostic and corrective methods for contractile activity disturbance making an impact to purinergic system. A way to predict a protracted pregnancy and special considerations for induced labor management were suggested. The reported clinical case indicates usefulness of protracted pregnancy prevention and introducing of the developed series of preventive measures to a wide practice aiming to obtain healthy newborns and to reduce pathological labor occurrence.

Due to the increasing prevalence of depression, it is necessary to improve medical care to manage the disease. The problems of regulation of medical care quality are analyzed in the article. It is established that the problems are connected both with the general economic condition of Russia, and with the problems in regulation of activity. The second group of problems includes the absence of approved clinical recommendations, mixing of different nosologies in the Standards and Criteria of quality, incomplete set of examinations necessary for patients with depression. Further economic development and approval of the Clinical Guidelines should improve the quality and availability of care for depressed patients.

Atrial fibrillation is one of the main types of arrhythmia; it leads to deterioration in haemodynamics, a decrease in patient’s quality of life, the development of complications such as stroke, a decrease in tolerance to physical stress and ultimately death. The reported prevalence of atrial fibrillation among the general population is 0.4%–1%. The incidence of atrial fibrillation has been found to increase with age such that every 10-year increase in age doubles the incidence of this disease. The incidence of coronary heart disease also increases with age. Current studies have shown an increase in concomitant diseases such as coronary heart disease and atrial fibrillation; these pose a serious health threat and increase the risk of patient death. The present review discusses surgical methods for treating long-standing, persistent atrial fibrillation in patients with coronary heart disease based on radiofrequency and cryoablation with simultaneous coronary artery bypass grafting. The present review revealed that biatrial ablation allows achieving high levels of markers that indicate atrial fibrillation recurrence-free survival following simultaneous surgical correction of coronary heart disease in the long-term postoperative period; however, patients undergoing this procedure require permanent pacemaker implantation due to the high incidence of irreversible sinus node dysfunction caused by the exposure to additional ablation lines in the right atrium. Published articles were searched from January to July 2019 using PubMed, eLIBRARY, Elsevier and MEDLINE.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributions Conception and study design: A.T. KalybekovaDrafting the article: A.T. Kalybekova, A.A. AlmazovCritical revision of the article: A.T. Kalybekova, S.S. RahmonovFinal approval of the version to be published: A.T. Kalybekova, S.S. Rahmonov, A.M. Chernyavskiy, A.A. Almazov, G.P. Narcissova, S.P. Mironenko

Цель исследования презентация возможностей нового программного модуля HeartModel (НМ) для автоматизированной трехмерной реконструкции объемов и архитектоники левых камер сердца в условиях кардиохирургической клиники. Материал и методы. Проведен анализ работы программного обеспечения НМ, установленного на ультразвуковой системе экспертного класса EpiQ-7, с использованием матричного фазированного трансторакального датчика Х5-1. Для демонстрации возможностей программы была проведена трех- мерная реконструкция левых камер сердца у 9 пациентов. Результаты. Программа НМ автоматически рассчитывает систолический и диастолический объемы левого желудочка (ЛЖ), длину полости, фракцию выброса, а также систолический объем левого предсердия (ЛП). Таким образом, применение методики НМ значительно сокращает время проведе- ния исследования, так как освобождает врача от необходимости вручную определять по ЭКГ систолу и диастолу, трассировать контур ЛЖ, а затем отдельно, тоже вручную, рассчитывать объем ЛП други- ми методиками, заложенными в компьютерную программу аппарата. Заключение. Все особенности сердца при различных типах патологии должны быть предельно точ- но визуализированы и оценены для разработки оптимальной стратегии и тактики лечения. Появление нового программного обеспечения HeartModel открывает перед врачом ультразвуковой диагностики новые возможности в оценке геометрии, объемов и архитектоники левых камер сердца.

Objective: to assess dynamics of diastolic function for detection of development of diastolic dysfunction (DD) and it’s causes, to evaluate the effect of DD on prognosis in the postoperative period in patients with acquired heart diseases.Materials and methods. We included in this study 112 patients with aortic and mitral valve diseases (90 men, 22 women, median age 51 [35; 57] years). All patients underwent echocardiography (echo), tissue Doppler, speckle tracking echo prior to surgery, in the early postoperative period (8–14 days) and in 12–36 months after surgery. In 28 patients dynamic contrast-enhanced magnetic resonance imaging was also performed. Patients were divided into groups according to prognosis: group 0 – without complications; group 1 – with postoperative heart failure (HF) and preserved left ventricular ejection fraction (EF); group 2 – with HF and EF 14, left atrial (LA) volume index >34 ml / m2, peak tricuspid regurgitation velocity >2.8 m / sec.Results. Initially diastolicLV function was normal in 34 of 112 patients (30.4 %), in early postoperative period DD emerged in 9 (26.5 %) of these patients. The appearance of LV DD was associated with decrease of septal es immediately after surgery and its subsequent progressive decline in the long-term postoperative period from 8.5±0.71 to 4.6 ±0.53 cm / sec (p=0.005). Worsening of diastolic function and lowering of septal velocity was detected namely in patients with presence of fibrosis. In the group of other patients in whom fibrosis was not studied and the degree of DD increased there was a transient decrease of lateral el (from 10.2±3.1 to 7.5±2.43 cm / sec, p=0.035) and an increase of the E / el (from 10.53±4.07 to 14.5±5.23, p=0.05) in the early period after the operation. There were no correlations between DD and LV EF,LV volumes, and development of arrhythmias. The prognostic model for DD included average longitudinal deformation of LA (global LA longitudinal strain) and E / e ratio on the tricuspid lateral annular velocity.Conclusions. Appearance of DD in postoperative period after correction of acquired heart defects was due to damage of the septal diastolic function which correlated with fibrosis and was indicative of inadequate myocardial protection. The model of development of heart failure with normal EF after operation was designed.

A collection of 183 monoconidial isolates of the causal agent of wheat tan spot Pyrenophora tritici-repentis was created. It is represented by 7 populations of different geographical origins isolated in 2017 and 2018: two “southern” populations from Krasnodar and South Kazakhstan (Almaty), two “northern” populations – from Finland and the Northwest and West Siberian (Northern Kazakhstan, Chelyabinsk and Omsk) regions of Russian Federation. The composition of races in populations and the presence of the ToxA and ToxB genes in the pathogen isolates were determined by PCR. ToxB gene was not detected in the isolates tested. All southern population isolates possessed ToxA gene (ToxA+). However, the results of virulence assays and genetic tests did not coincide: 14 % of the isolates from the South Kazakhstan population and 61 % of the Krasnodar population did not induce necrosis on the leaves of Glenlea, i.e. they were nec?, and did not possess the necrosis inducing toxin Ptr ToxA and other necrosis toxins. The opposite situation was observed in the “northern” and Western Siberian populations of the pathogen with the ToxA+ fraction varying from 5.5 % to 66 %, but the quote of nec+ isolates was significantly higher than that of ToxA+ isolates. This finding indicates the dominance of isolates producing necrosis-inducing toxin(s) other than Ptr ToxA in these populations. Our work shows that the P. tritici-repentis-wheat pathosystem is not restricted to the interactions of three necrotrophic effectors (ToxA, ToxC, ToxB) and three susceptibility genes (Tsn1, Tsc1, Tsc2) and probably involves other additional effectors and susceptibility genes or other types of parasite-host relationships. Additionaly, the isolates with impaired ToxA gene expression prevail in the southern populations of the pathogen. The maintenance of ToxA+ nec- isolates in the southern populations indicates the existence of additional functions of the ToxA gene, important for the competitiveness of the fungal isolates.

To investigate diagnostic role of 18F-fluorodeoxyglucose PET/CT in patients with suspected vascular graft (VG) infection.A prospective analysis included data of 30 PET/CT examinations for suspected infection of aortic VG (PET/CT confirmed VG infection in 94% (17/18) and excluded in 50% (6/12) of cases. False PET/CT results were obtained in 23% (7/30) cases: false positive in 6 cases and false negative in 1 case. Thus, sensitivity, specificity and diagnostic accuracy of PET/CT were 94%, 50% and 77%, respectively; positive and negative predictive value - 74% and 86%. PET/CT results allowed correct reclassifying 33% (10/30) of cases. VG infection was confirmed in 73% (8/11) of patients with initially «possible» diagnosis and excluded in 17% (2/12) of patients with initially «rejected» infection. Moreover, whole body PET/CT revealed unknown inflammation foci outside VG in 73% (22/30) of cases. These data were applied to correct treatment approach in 80% (24/30) of cases.Our results showed high efficacy of 18F-fluorodeoxyglucose PET/CT in the diagnosis of VG infection. Despite low specificity, this technique has high sensitivity and accuracy that allowed reclassifying 33% of cases.Изучить диагностические возможности ПЭТ/КТ с 18F-фтордезоксиглюкозой у больных с подозрением на инфекцию сосудистых протезов (СП).В проспективный анализ включены результаты 30 ПЭТ/КТ-исследований, выполненных при подозрении на инфекцию СП в различные сроки (медиана 48 мес) после протезирования различных отделов аорты (Результаты ПЭТ/КТ позволили корректно диагностировать инфекционный процесс в зоне СП в 94% (17 из 18) случаев и исключить его наличие в 50% (6 из12) случаев. У 23% (7 из 30) пациентов получены ложные результаты — ложноположительные (Полученные данные свидетельствуют о высокой информативности ПЭТ/КТ с 18F-фтордезоксиглюкозой в диагностике инфекции СП: несмотря на низкую специфичность, метод обладает высокой чувствительностью и точностью, что позволило корректно реклассифицировать 33% случаев анализируемой группы.

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called Coronavirus Disease 2019 (COVID-19). Control of SARS-CoV-2 spread will depend on vaccine-induced or naturally acquired protective herd immunity. Until then, antiviral strategies are needed to manage COVID-19, but approved antiviral treatments, such as remdesivir, can only be delivered intravenously. Enisamium (laboratory code FAV00A, trade name Amizon®) is an orally active inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. Here we show that enisamium can inhibit SARS-CoV-2 infections in NHBE and Caco-2 cells. In vitro, the previously identified enisamium metabolite VR17-04 directly inhibits the activity of the SARS-CoV-2 RNA polymerase. Docking and molecular dynamics simulations suggest that VR17-04 prevents GTP and UTP incorporation. To confirm enisamium’s antiviral properties, we conducted a double-blind, randomized, placebo-controlled trial in adult, hospitalized COVID-19 patients, which needed medical care either with or without supplementary oxygen. Patients received either enisamium (500 mg per dose) or placebo for 7 days. A pre-planned interim analysis showed in the subgroup of patients needing supplementary oxygen (n = 77) in the enisamium group a mean recovery time of 11.1 days, compared to 13.9 days for the placebo group (log-rank test; p=0.0259). No significant difference was found for all patients (n = 373) or those only needing medical care (n = 296). These results thus suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis and that enisamium treatment shortens the time to recovery for COVID-19 patients needing oxygen.Significance statementSARS-CoV-2 is the causative agent of COVID-19. Although vaccines are now becoming available to prevent SARS-CoV-2 spread, the development of antivirals remains necessary for treating current COVID-19 patients and combating future coronavirus outbreaks. Here, we report that enisamium, which can be administered orally, can prevent SARS-CoV-2 replication and that its metabolite VR17-04 can inhibit the SARS-CoV-2 RNA polymerase in vitro. Moreover, we find that COVID-19 patients requiring supplementary oxygen, recover more quickly than patients treated with a placebo. Enisamium may therefore be an accessible treatment for COVID-19 patients.

Purpose To investigate the diagnostic performance of 18F-FDG PET/CT in patients with suspected prosthetic valve infective endocarditis (IE), prosthetic aortic and intracardiac device infection. Methods The prospective analysis included results of PET/CT examinations performed in 60 patients with fever of unknown origin after cardiac surgery (median time 29 months): valve replacement (n=26), intracardiac device implantation (n=19), both procedures (n=8), Bentall-de-Bono surgery (n=7). According to the Duke criteria most patients – 90% (54/60) – had possible (n=42) and rejected (n=12) diagnosis of IE; 6 patients had definite IE. PET/CT scan was performed 90 min after intravenous injection of 18F-FDG (175–200MBq). All patients underwent strict carbohydrate-free diet and fasted for at least 15–18 hours. Final diagnosis was based on clinical, laboratory, instrumental and intraoperative (n=41) data: confirmed in 40 and ruled out in 20 patients. Results PET/CT results correctly confirmed the infectious process in the prosthetic valve area, aortic prosthesis or along the intracardiac device in 93% (37/40) and ruled it out in 75% (15/20) patients. False results were obtained in 13% (8/60) – positive (n=5) and negative (n=3). Thus, in the analyzed group of patients (n=60), the sensitivity, specificity and diagnostic accuracy of PET/CT with 18F-FDG in the diagnosis of IE were 93%, 75% and 83%, respectively; positive and negative predictive value – 88% and 83%. In patients with possible IE according to the Duke criteria, true PET/CT results were obtained in 86% (36/42) – positive (n=28) and negative (n=8). In 7% (4/60) of patients – the diagnosis was based only on PET/CT, while initially, according to the Duke criteria, it was rejected. In addition, in 40% (24/60) of patients of the analyzed group, whole body PET/CT revealed other than valve and device, previously unknown foci of inflammation: in the lungs (n=6), in the sternum (n=6), in the area of the native valve (n=3), in the mediastinum (n=4), other (n=13). Conclusions 18F-FDG PET/CT proved to be highly informative for the diagnosis of infectious processes in the heart and vessels in patients after cardiac surgery. The inclusion of PET/CT in the diagnostic algorithm for this category of patients reduces the number of patients with possible IE according to the Duke criteria. Funding Acknowledgement Type of funding source: None

Low success rates during drug development are due, in part, to the difficulty of defining drug mechanism‐of‐action and molecular markers of therapeutic activity. Here, we integrated 199,219 drug sensitivity measurements for 397 unique anti‐cancer drugs with genome‐wide CRISPR loss‐of‐function screens in 484 cell lines to systematically investigate cellular drug mechanism‐of‐action. We observed an enrichment for positive associations between the profile of drug sensitivity and knockout of a drug's nominal target, and by leveraging protein–protein networks, we identified pathways underpinning drug sensitivity. This revealed an unappreciated positive association between mitochondrial E3 ubiquitin–protein ligase MARCH5 dependency and sensitivity to MCL1 inhibitors in breast cancer cell lines. We also estimated drug on‐target and off‐target activity, informing on specificity, potency and toxicity. Linking drug and gene dependency together with genomic data sets uncovered contexts in which molecular networks when perturbed mediate cancer cell loss‐of‐fitness and thereby provide independent and orthogonal evidence of biomarkers for drug development. This study illustrates how integrating cell line drug sensitivity with CRISPR loss‐of‐function screens can elucidate mechanism‐of‐action to advance drug development.

Community-acquired pneumonia (CAP) is one of the most relevant problems of modern medicine. Today, CAP takes 4thplace in the structure of mortality (after cardio­vascular, cerebrovascular diseases and malignant neoplasms) and 1stplace among all deaths from infectious diseases. The aim of the study is to assess the level of general physician’ and senior medical students’ basic knowledge in CAP treatment. The article represents the results of anonymous prospective surveys within the framework of the second stage of KNOCAP multi-centered research project (full name of the project «The assessment of physician’ and students’ knowledge of community-acquired pneumonia basics») aimed at accessing the knowledge and preferences of doctors and students on the fundamental issues in diagnosis and treatment of community-acquired pneumonia. The survey conducted in 2017-2019 involved 588 physicians and 394 students from seventeen Russian, Kyrgyzstan and Ukrainian centers. The method of anonymous questioning was used in this study, for which an original questionnaire was developed on the basis of current clinical recommendations. The following fundamental questions caused the greatest difficulties in the respondents: terms for a repeated X-ray examination in positive dynamics of CAP treatment, the choice of main diagnostic criteria of CAP, the choice of the typical mistakes of CAP treatment, the choice of the initial antimicrobial therapy. In general, the respondents’ knowledge in CAP patients’ management deviates significantly from the current clinical guidelines, as of 2010, and from the new clinical guidelines draft, 2018-2019. Currently, there is a need to increase the level of knowledge and improve the professional activities of therapists and senior medical students, as a multicenter section of the knowledge and preferences of specialists in many issues revealed their insufficient level for the correct management of patients with CAP.