Факторы риска развития инфекционно-воспалительного процесса нижних мочевых путей

Persistence as well as high survival rate and resistance of microorganisms belong to the key reasons promoting symptoms of lower urinary tract diseases. They can stay active for a long time and can substantially deteriorate the life quality of patients suffering from chronic infections and inflammations in the wall of the urinary bladder even after the eradication of the pathogen. Recent studies in the field of clinical microbiology reflect serious qualitative and quantitative changes in the infection incidence structure, which is mainly related to changes in the bacterial pathogenicity. Pathogenicity island genes control the synthesis of different adhesins, invasins, hemolysins and toxins (hemolysin, cytotoxic necrotizing factor type 1, etc.) as well as iron ion absorption system, which are essential for the pathogen propagation and activity in tissues. The determination of genetic determinants will provide a new insight into the bacterial evolution process and will help to understand the reason of prompt formation and propagation of virulent strains as well as fast development of the infection and inflammation in the lower urinary tract, which may explain different severity of the pathology and symptoms of the lower urinary tract.Персистенция микроорганизмов, их высокая выживаемость и резистентность - одни из причин, поддерживающие симптомы заболеваний нижних мочевых путей. Они могут длительно сохраняться и значительно снижать качество жизни пациентов с рецидивирующим хроническим инфекционно-воспалительным процессом в стенке мочевого пузыря даже после эрадикации возбудителя. В последние годы исследования в клинической микробиологии отражают серьезные качественные и количественные изменения в структуре инфекционной заболеваемости, что в большей степени связывают с изменением патогенности бактерий. Гены «островов патогенности» контролируют синтез различного типа адгезинов, инвазинов, гемолизинов, токсинов (гемолизина, цитотоксического некротизирующего фактора-1 и др.), системы поглощения ионов железа, важных для размножения и жизнедеятельности возбудителя в тканях. Обнаружение генетических детерминант дает возможность по-новому взглянуть на процесс эволюции бактерий, понять причину быстрого формирования и распространения вирулентных штаммов и развитие инфекционновоспалительного процесса в нижнем отделе мочевого тракта, что может объяснять различную тяжесть патологического процесса и выраженность симптомов поражения нижних мочевых путей

Клиническое исследование отечественного фибринселективного тромболитического препарата Фортелизин® (III фаза)

The clinical trial of fibrinselective thrombolytic agent Fortelyzin® (III phase) showed the comparative efficacy and safety with Actilyse® in patients with acute myocardial infarction and obtained data permitted to recommend it for clinical usage.Проведенное исследование лекарственного препарата Фортелизин®, вводимого болюсно и болюсно-инфузионно у больных с острым инфарктом миокарда с подъемом сегмента ST, показало сравнимую с Актилизе® эффективность и безопасность исследуемого препарата и позволило рекомендовать его для медицинского применения

Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial

Background: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. Methods: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0–1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0–1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. Findings: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89–89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI –1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). Interpretation: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Funding: The Russian Academy of Sciences. © 2021 Elsevier Lt

Thimerosal in childhood vaccines contributes to accumulating mercury toxicity in the kidney

Mercury (Hg) is a hazardous chemical that accumulates in many cells and tissues, thereby producing toxicity. The kidney is a key target organ for Hg accumulation and toxicity. The contributing factors to Hg accumulation in humans include: (1) elemental and inorganic Hg exposure, often occurring by inhalation of Hg vapors; (2) exposure to methyl Hg (meHg), for example, through contaminated seafood; and (3) exposure to ethyl mercury (etHg) via thimerosal-containing vaccines. Systematic investigations on the toxic effects of etHg/thimerosal on the nervous system were carried out, and etHg/thimerosal emerged as a possible risk factor for autism and other neurodevelopmental disorders. There is, however, little known about the mechanisms and molecular interactions underlying toxicity of etHg/thimerosal in the kidney, which is the focus of the current review. Susceptible populations such as infants, pregnant women, and the elderly are exposed to etHg through thimerosal-containing vaccines, and in-depth study of the potential adverse effects on the kidney is needed. In general, toxicity occurring in association with different forms of Hg is related to: intracellular thiol metabolism and oxidative stress reactions; mitochondrial function; intracellular distribution and build-up of calcium; apoptosis; expression of stress proteins; and also interaction with the cytoskeleton. Available evidence for the etHg-induced toxicity in the kidney was examined, and the main mechanisms and molecular interactions of cytotoxicity of etHg/thimerosal exposure in kidney described. Such accumulating knowledge may help to indicate molecular pathways that, if modulated, may better handle Hg-mediated toxicity

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiolog

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and 651 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and 64 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores 642. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007