Significance of individual management plan for the patients with hereditary lymphangioedema during pregnancy and lactation, and in newborns

Hereditary angioedema (HAE) is a genetically caused orphan disease with a high risk of developing life-threatening attacks, thus requiring availability for up-to-date information on this problem for the doctors of any specialties. A limited number of observations determine the value of the analysis for each clinical case. Many facets of clinical manifestations, a list of predisposing and triggering factors, as well as limitations of some diagnostic and therapeutic algorithms, require the development of individual management schemes under distinct clinical situations. In this paper, we present the unique clinical cases with certain limitations, describing unexpected onset of the disease in the course of pregnancy, management aspects during delivery and post-delivery periods in a women with a previously confirmed HAE diagnosis. Adapted diagnostic algorithms of postnatal diagnostic verification are presented for children with burdened genetic history. We express some assumptions about involvement of a multidisciplinary team of specialists, personalized approach to building a management plan with an “online” correction depending on observation stage of НАЕ patient

Discovery of strongly variable X-ray polarization in the neutron star low-mass X-ray binary transient XTE J1701-462

CONTEXT: After about 16 years since its first outburst, the transient neutron star low-mass X-ray binary XTE J1701−462 turned on again in September 2022, allowing for the first study of its X-ray polarimetric characteristics by a dedicated observing program with the Imaging X-ray Polarimeter Explorer (IXPE). AIMS: Polarimetric studies of XTE J1701−462 have been expected to improve our understanding of accreting weakly magnetized neutron stars, in particular, the physics and the geometry of the hot inner regions close to the compact object. METHOD: The IXPE data of two triggered observations were analyzed using time-resolved spectroscopic and polarimetric techniques, following the source along its Z-track of the color–color diagram. RESULTS: During the first pointing on 2022 September 29, an average 2–8 keV polarization degree of (4.6 ± 0.4)% was measured, the highest value found up to now for this class of sources. Conversely, only a ∼0.6% average degree was obtained during the second pointing ten days later. CONCLUSIONS: The polarimetric signal appears to be strictly related to the higher energy blackbody component associated with the boundary layer (BL) emission and its reflection from the inner accretion disk, and it is as strong as 6.1% and 1.2% (> 95% significant) above 3–4 keV for the two measurements, respectively. The variable polarimetric signal is apparently related to the spectral characteristics of XTE J1701−462, which is the strongest when the source was in the horizontal branch of its Z-track and the weakest in the normal branch. These IXPE results provide new important observational constraints on the physical models and geometry of the Z-sources. Here, we discuss the possible reasons for the presence of strong and variable polarization among these sources

Discovery of a variable energy-dependent X-ray polarization in the accreting neutron star GX 5-1

We report on the coordinated observations of the neutron star low-mass X-ray binary (NS-LMXB) GX 5−1 in X-rays (IXPE, NICER, NuSTAR, and INTEGRAL), optical (REM and LCO), near-infrared (REM), mid-infrared (VLT VISIR), and radio (ATCA). This Z-source was observed by IXPE twice in March-April 2023 (Obs. 1 and 2). In the radio band the source was detected, but only upper limits to the linear polarization were obtained at a 3σ level of 6.1% at 5.5 GHz and 5.9% at 9 GHz in Obs. 1 and 12.5% at 5.5 GHz and 20% at 9 GHz in Obs. 2. The mid-IR, near-IR, and optical observations suggest the presence of a compact jet that peaks in the mid- or far-IR. The X-ray polarization degree was found to be 3.7%±0.4% (at 90% confidence level) during Obs. 1 when the source was in the horizontal branch of the Z-track and 1.8%±0.4% during Obs. 2 when the source was in the normal-flaring branch. These results confirm the variation in polarization degree as a function of the position of the source in the color-color diagram, as for previously observed Z-track sources (Cyg X-2 and XTE 1701−462). Evidence of a variation in the polarization angle of ∼20° with energy is found in both observations, likely related to the different, nonorthogonal polarization angles of the disk and Comptonization components, which peak at different energies

Сравнительный анализ применения тоцилизумаба при тяжелых COVID-19-ассоциированных пневмониях у пациентов разных возрастных групп

According to accumulated clinical data, one of the causes of severe damage to lung epithelial cells associated with SARS-CoV-2 (2019-nCoV) is an acute, timely underestimated "cytokine storm" (cytokine cascade, hypercytokinaemia) with characteristic signs of an expressed hyper-inflammatory syndrome with subsequent polyorganic failure. The study presents the results of the analysis of the effectiveness of tocilizumab therapy (TCZ) in patients (n = 181) of different age groups with developed pneumonia caused by SARS-CoV-2. The aim of the study was to evaluate the effectiveness of TCZ therapy in patients of different age groups with developed pneumonia in the frame of COVID-19. Methods. Patients (n = 181) with community-acquired pneumonia caused by coronavirus SARS-CoV-2 are included in a one-center, non-randomized, prospective study to evaluate the effectiveness of TCZ therapy conducted at the State Public Health Institution "City Clinical Hospital No.52" of the Moscow City Health Department. Patients were divided into 3 age subgroups – up to 50 years, 50–70 years and over 70 years. Patients with community-acquired SARS-CoV-2-induced pneumonia receiving non-invasive oxygen support and patients who had artificial lung ventilation (ALV) were given a single dose of 400 mg of TCZ in addition to basic therapy. Results. There are no significant differences between age groups in the severity of pneumonia according to the data of the computed tomography (CT), however, a more severe condition and a higher mortality rate (p < 0.001) were reliably observed in patients over 70 age compared to the other age groups. After TCZ treatment in patients of each age group, the severity of the condition assessed on the National Early Warning Score (NEWS2) has been significantly reduced compared to the baseline. Conclusion. According to the data of the pilot study the efficacy and safety of TCZ in patients of all presented age groups with COVID-associated pulmonary tissue lesion and signs of "cytokine storm" was demonstrated. At the same time, patients up to 50 years after the therapy of TCZ managed to achieve greater clinical efficiency compared to patients in other groups. According to the severity of the state and laboratory criteria, the lowest clinical efficacy of TCZ therapy was observed in patients over 70 years of age; as a consequence, the highest mortality rate was observed in the same group. At the same time, the TCZ therapy has not had a positive impact on the change of laboratory values and the severity of the disease in case of unfavorable outcome. Согласно накопленным клиническим данным, одной из причин тяжелых повреждений клеток эпителия легких, ассоциированных с SARS-CoV-2 (2019-nCoV), является острый, вовремя недооцененный синдром «цитокинового шторма» (цитокиновый каскад, гиперцитокинемия) с характерными признаками выраженного гипервоспалительного синдрома с последующей полиорганной недоста - точностью. В работе представлены результаты анализа эффективности терапии тоцилизумабом (ТЦЗ) у пациентов (n = 181) разных возрастных групп с развившейся пневмонией в рамках COVID-19. Целью исследования явилась оценка эффективности терапии ТЦЗ у пациентов разных возрастных групп с развившейся пневмонией, вызванной SARS-CoV-2. Материалы и методы. В одноцентровом нерандомизированном проспективном исследовании оценки эффективности терапии ТЦЗ, проведенном на базе Государственного бюд жетного учреждения здравоохранения «Городская клиническая больница № 52» Департамента здравоохранения города Мос - квы, приняли участие пациенты (n = 181) с внебольничной пневмонией, вызванной коронавирусом SARS-CoV-2. Больные были распределены в 3 возрастные подгруппы: до 50 лет, 50–70 лет, старше 70 лет. Пациентам с внебольничной пневмонией, вызванной SARS-CoV-2, получающим неинвазивную кислородную поддержку, и больным, у которых проводилась искусственная вентиляция легких (ИВЛ), в до полнение к основной терапии назначен ТЦЗ однократно в дозе 400 мг. Результаты. Достоверных различий между возрастными группами по тяжести пневмонии по данным компьютерной томографии (КТ) не выявлено, однако отмечено достоверно более тяжелое состояние и более высокий уровень смертности (p < 0,001) у больных старше 70 лет по сравнению с остальными возрастными группами. После терапии ТЦЗ у больных каждой из возрастных групп тяжесть состояния, оцененная по шкале National Early Warning Score (NEWS2), достоверно снизилась по сравнению с исходными показателями. Заключение. По данным пилотного исследования продемонстрирована эффективность и безопасность применения ТЦЗ у пациентов всех представленных возрастных групп с COVID-ассоциированным повреждением легочной ткани и признаками «цитокинового шторма». При этом у пациентов до 50 лет после терапии ТЦЗ удалось добиться бόльшей клинической эффективности по сравнению с больными остальных групп. По степени тяжести состояния и лабораторным критериям самая низкая клиническая эффективность терапии ТЦЗ отмечена у пациентов старше 70 лет; как следствие, в этой же группе отмечен самый высокий уровень смертности. При этом в случае неблагоприятного исхода терапия ТЦЗ не оказывала положительного влияния на изменение лабораторных показателей и степень тяжести заболевания.

Gradient of luminal narrowing of internal carotid artery on atherosclerotic plaque as risk factor for cerebral ischemic damage

Aim. To study the clinical significance of the gradient of narrowing of arterial lumen (GNL) for atherosclerotic stenosis of the internal carotid artery (ICA) as a risk factor for ischemic brain damage.Material and methods. We proposed a new parameter of hemodynamic severity of ICA atherosclerotic stenosis — GNL. It calculated as ratio of the difference in the ICA cross section areas on the stenotic lesion and the near non-stenotic region to the distance between them: Snorm — Sstenosis)/Dnorm — stenosis, mm2 /mm. We examined 25 patients with advanced atherosclerosis and with uni(n=22) or bilateral (n=3) ICA stenosis >50% according to European Carotid Surgery Trial, and 11 individuals without ICA stenosis. Each participant underwent magnetic resonance angiography (MRA) of the carotid arteries with reconstruction of the arteries from C6-C7 level to the parietal bones, and the GNL was calculated. The thickness of the baseline slice was 0,8-1 mm. Each subject also underwent cerebral magnetic resonance imaging (MRI) in T1-, T2-, PD-, flair-weighted protocols. Results. Patients were divided into groups: group 1 (n=12) — without ischemic injury in the ICA system, and group 2 (n=13)  — with MRI signs ischemic injury history. The groups did not differ in proportion of stenosis (74,9±4,25% and 77,8±3,8%, p<0,05), ICA lumen area on the stenotic lesion (1,05±0,18 mm2 and 1,14±0,17 mm2 , p<0,05) and the ICA diameter at the non-stenotic region (4,30±0,32 mm and 4,9±0,29 mm, p<0,05). In control group, GNL was <0,75 mm2 /mm. Groups 1 and 2 significantly differed (2,47±0,41 mm2 /mm and 4,60±0,51 mm2 /mm, p<0,02). In group 2, 12 out of 13 patients had GNL >3,35 mm2 /mm, and, in group 1, 9 out of 12 — less than 3,35 mm2 /mm. GNL did not correlate significantly with other parameters of ICA stenosis. Two patients with the highest GNL in each group (5,5 and 8,6 mm2 /mm) had a fatal ischemic stroke within six monthsConclusion. Firstly, proposed parameter of stenosis hemodynamic severity GNL is independent, informative and prognostically important indicator for carotid artery atherosclerotic lesion

HIGH-RESOLUTION CONTRAST-ENHANCED MRI IN DIFFERENTIAL DIAGNOSIS OF TYPE OF CAROTID PLAQUE AND IT'S RELATIONSHIP TO THE ISCHEMIC BRAIN DAMAGE

Aim of the study. We have compared in patients with carotid atherosclerosis the patterns of contrast enhancement of atherosclerotic plaque with presence of cerebral stroke, by using of high-resolution contrast-enhanced carotid MRI.Material and methods. The patients 'population comprised 26 persons with either monolateral (14 pts) or bilateral (12 pts) stenosis of internal carotid artery for over 70% of lumen. In 15 (10-monolateral, 5 bilateral stenosis) there was recent stroke in acute or subacute stage, whereas 11 were symptom-free. In everybody contrast-enhanced study of atherosclerotic plaque was carried out with T1-w high-resolution MRI (paramagnetic as 2 ml of 0.5 mol solution per 10 kg of BW).Results and discussion. In control persons there was a mild increase in T1-w intensity of arterial wall of carotids? With IE not more than 1.08. In patients without stroke there was moderate increase in plaque T-1w intensity up to 1.14 ± 0.07. In ishaemic stroke patients there was significant rise in intensity of T1-w of homolateral plaque (IE = 1.35 ± 0.06), and also of T1-w of arterial wall as whole (IE = 1.19 ± 0.05).Conclusion. Further detailed study of high-resolution MRI of carotids is worth in order to obtain better imaging of atherosclerotic lesions and also better evaluation of risk of stroke in patients suitable for carotid endarterectomy

Бронхиальная астма и ожирение: поиск терапевтических моделей

A phenotype-based approach to treatment of bronchial asthma draws the growing attention of experts worldwide. One of asthma phеnotypes is comorbidity of asthma and overweight (including obesity). Some features of this phenotype have recently been described in molecular studies. An intensive search of relationships between phenotype, genotype and pathogenic mechanisms of the disease is suggested to be useful for development of effective therapeutic algorithm with the highest predictive value in this cohort of patiens. Все большее внимание экспертов уделяется фенотип-обоснованному подходу к лечению пациентов с бронхиальной астмой (БА). Одним из основных клинических фенотипов является сочетание БА и избыточной массы тела, а в некоторых случаях – ожирения. Ряд клинических особенностей этого тандема объясняется результатами молекулярно-генетических исследований. Активный поиск взаимосвязей между фенотипом, генотипом и механизмом развития заболевания позволит разработать эффективный терапевтический алгоритм, наиболее прогностически оправданный у данной подгруппы пациентов.