Efficacy and safety of ocrelizumab in patients with relapsing multiple sclerosis: Real-world experience of two Swiss multiple sclerosis centers.

BACKGROUND: Ocrelizumab (OCR) is a humanized monoclonal antibody directed against CD-20 positive lymphocytes, mainly B-lymphocytes. OCR is approved for treatment of primary progressive (PPMS) and relapsing multiple sclerosis (RMS). This study aims to provide real-world safety and efficacy data of people with RMS treated with OCR in two Swiss Multiple Sclerosis (MS) centers. METHODS: We have conducted a retrospective data analysis using the patient cohorts from the Cantonal Hospital Aarau and Bern University Hospital (RMS: n = 235). Statistical analyses were performed with Mann-Whitney U-Test, Chi-squared test and Spearman-Rho-Correlation. Adjustment for multiple testing was performed by Bonferroni procedure. RESULTS: After initiation of OCR, there was a decrease in disease activity in RMS patients. In our study, 152/190 (80.0 %) RMS patients fulfilled the criteria for NEDA-3 12 months and 88/104 (84.6 %) showed NEDA-3 24 months after OCR initiation. The most frequent adverse events (AEs) in our study were infections, taking place in 78/235 (33.2 %) RMS patients. COVID-19 was the most common infection, followed by urinary infections and other respiratory infections and infectious adverse events occurred significantly more frequent in patients with reduced IgG serum concentration. CONCLUSIONS: Our real-world study showed OCR being associated with low rates of any type of MS disease activity as indicated by NEDA-3. The adverse event profile is comparable to the known events especially infections and an association between infections and reduced IgG serum concentration was found.

Visual hallucinations after resection of cerebral metastases: two patients with complex phantom images.

PURPOSE: Complex visual hallucinations are rarely seen in neurooncology. They are commonly observed alongside psychotic symptoms in schizophrenia or dementia, in Parkinson's or Lewy-body disease, after opioid medications or anesthesia, and, in particular, they appear with visual impairments. METHODS: Here we report two normal-sighted and mentally healthy patients with unusual visual hallucinations after the resection and irradiation of brain metastases, the main features of which were persistent colorful and meaningful images with hallucinatory perseveration. RESULTS: These cases demonstrate the occurrence of complex visual hallucinations after resection of visual cortices as an effect of deafferentation, so-called visual release hallucinations or phantom images, similar to phantom pain after amputation of a limb. CONCLUSION: This case serves to heighten awareness in the radiooncology practitioner of the occurrence of visual release hallucinations (Charles Bonnet syndrome) related to multidisciplinary treatment of brain metastases.

[FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity]. / FRF23-indutsirovannaya osteomalyatsiya opukholevogo geneza s lokalizatsiei novoobrazovaniya v barabannoi polosti.

Tumor induced osteomalacia is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients complain of progressive bone pain, muscle weakness and brittle fractures. Delayed diagnosis of osteomalacia caused by a tumor is often found in clinical practice. When verifying the exact localization of the neoplasm, radical removal within healthy tissues is recommended. The article considers a clinical example of FGF23 tumor induced osteomalacia with localization of neoplasm in the tympanic cavity.

[Heart Failure With Low and Preserved Left Ventricular Ejection Fraction - are These Two Different Independent Diseases or One Disease, but at Different Stages of its Progression? How Does This Affect the Choice of Therapy and Its Effectiveness?]

The article discusses the question of whether it is possible to conclude that any heart failure (HF), throughout the entire range of left ventricular ejection fractions (LVEF), is a single holistic disease, based on the "external" similarity of treatments for reduced (HFrEF) and preserved (HFpEF) LVEF, and that positioning HFpEF and HFrEF as separate independent diseases is not valid.

[New effects of a topical antimicrobial (agent) in the treatment of acute tonsillopharyngitis]. / Novye effekty topicheskogo antimikrobnogo preparata v lechenii ostrogo tonzillofaringita.

Sore throat is the leading symptom of acute tonsillopharyngitis associated with previous acute respiratory viral infections, including COVID-19. The pathogenesis of these nosologies is based on the cumulative result of the primary direct damaging effect of viruses and secondary alternative inflammatory changes in the mucosal epithelium in the focus of infection, which, against the background of changes in the functions of the regional microbiota, leads to the development of viral-bacterial inflammation that goes beyond the protective-reparative level. In the treatment of acute tonsillopharyngitis after exclusion of GABHS etiology, topical etiotropic drugs are often used. It is desirable to achieve a uniform distribution of active ingredients, and to maximize the use of additional pharmacological capabilities (irrigation-eliminative action, reparative effect). To build up the evidence base for the effectiveness of just such medicines on the basis of the Department of Otorhinolaryngology of the Moscow State Medical University named after. A.I. Evdokimov, an observational prospective comparative study was conducted, using, in addition to the clinical assessment method, cytomorphological approaches (cytomorphometry). The results of the study demonstrated that gargling with a solution of hydroxymethylquinoxylindioxide (Dioxydin 0.25 mg/ml solution for topical application) in adult patients with acute tonsillopharyngitis provides rapid relief of pain, a decrease in the severity of inflammation symptoms, and also makes it possible to achieve limitation of the degree of destruction of the epithelium in the height of inflammation and a more complete and rapid recovery of the damaged mucous membrane by the time of recovery.

[What is "normal left ventricular ejection fraction" and its relationship with the pathogenesis and effectiveness of the treatment of heart failure].

The article focuses on modern views on the role and place of left ventricular ejection fraction (LV EF) in determining the status of cardiovascular patients (primarily patients with heart failure) in the algorithm for their diagnosis, treatment, and prediction of the outcome. Conclusions and recommendations on the use of LV EF in patients with chronic heart failure (CHF) are the following: 1) LV EF remains a familiar and convenient instrumental indicator not so much of myocardial contractility as of hemodynamics in general. Assessment of LV EF is useful for selection and ranking of CHF patients whereas the LV EF dynamics is useful for assessing the quality of their management. 2) In the entire population of cardiovascular patients, the "normal" LV EF (mortality nadir) is in the range of 60-65%. 3) LV EF demonstrates a U-shaped relationship with prognosis: in cardiovascular patients with LV EF below the mortality nadir, the relationship is inversely proportional, and above the mortality nadir, it is directly proportional. The question of the boundary between "normal" and "reduced" LV EF in terms of CHF syndrome remains open, but obviously, this boundary is most likely within the range of 50 to 60%. 4) LV EF determines the effectiveness of CHF treatment, but this rule is not applicable to all LV EF ranges and not to all classes of drugs.

[Diastolic heart failure: 20 years later. Сurrent issues of pathoge-nesis, diagnosis and treatment of heart failure with preserved LVEF].

Relevant aspects of the pathogenesis, diagnosis, And treatment of heart failure with preserved LV EFThis review analyzes results of studies of the recent decade that focus on epidemiology, mechanisms of development, diagnostic methods, and treatments of heart failure with preserved ejection fraction (HFpEF). As expected, the prevalence of HFpEF continues to increase due to the growing contribution of comorbidities to the structure of causes for chronic heart failure (CHF), such as arterial hypertension with left ventricular hypertrophy, obesity, chronic kidney disease, as well as due to ageing of the population and decreased contributions of ischemic heart disease and myocardial infarction. Concomitant diseases are a source of low-intensity microvascular inflammation, which is currently assigned a role of a trigger mechanism eventually provoking energy deficiency, disorders of cardiomyocyte relaxation, and diffuse myocardial fibrosis. Both these processes lead to increased heart muscle rigidity and abnormally high left ventricular filling pressure (LVFP). High LVFP is associated with the development of pulmonary venous congestion and impairment of alveolar blood oxygenation, which form the clinical picture of HFpEF. Detecting high LVEF with tissue Doppler echocardiography by the E / e' value became the instrumental basis for the HFpEF diagnostics. Recognition of inflammation and fibrosis as the key pathogenetic factors marked the main vector of modern therapy for HFpEF (anti-inflammatory and antifibrotic). The best implementation of this vector became possible with the advent of drugs from the class of angiotensin receptor and neprilysin inhibitors (ARNI), sodium-glucose cotransporter type 2 (SGLT2) inhibitors, and aldosterone antagonists. However, the efficacy of such treatments is evident only with the LV EF <60-65% while at higher values, the efficacy substantially decreases. This limitation may result from the heterogenous nature of the disease and requires more advanced methods for verification of HFpEF clinical phenotypes. Among such methods, transcriptomic, metabolomic, and proteomic approaches are considered. With the use of capabilities of the "machine learning" and the artificial intelligence, these approaches can become a new frontier in research to represent an important step towards personalized medicine for patients with HFpEF.

[Treatment of patients with heart failure and preserved ejection fraction: reliance on clinical phenotypes].

The article discusses the problem of improving the effectiveness of treatment of heart failure with preserved left ventricular ejection fraction (HFpEF). The relative "failure" of early studies with renin-angiotensin-aldosterone system inhibitors was largely due to the lack of understanding that patients with HFpEF represent a heterogeneous group with various etiological factors and pathogenetic mechanisms of the disease. Therefore, the so-called personalized approach should be used in the treatment of these patients. This approach is based on the identification of clearly defined disease phenotypes, each characterized by a set of demographic, pathogenetic, and clinical characteristics. Based on the literature and own experience, the authors consider four main phenotypes of HFpEF: 1) phenotype with brain natriuretic peptide "deficiency" syndrome associated with moderate/severe left ventricular hypertrophy; 2) cardiometabolic phenotype; 3) phenotype with mixed pulmonary hypertension and right ventricular failure; and 4) cardiac amyloidosis phenotype. In the treatment of patients with phenotype 1, it seems preferable to use the valsartan + sacubitril (possibly in combination with spironolactone) combination treatment; with phenotype 2, the empagliflozin treatment is the best; with phenotype 3, the phosphodiesterase type 5 inhibitor sildenafil; and with phenotype 4, transthyretin stabilizers. Certain features of different phenotypes overlap and may change as the disease progresses. Nevertheless, the isolation of these phenotypes is advisable to prioritize the choice of drug therapy. Thus, the diuretic treatment (preferably torasemide) should be considered in the presence of congestion, regardless of the HFpEF phenotype; the valsartan + sacubitril and spironolactone treatment is appropriate not only in the shortage of brain natriuretic peptide but also in the presence of concentric left ventricular hypertrophy (except for the amyloidosis phenotype); and the treatment with empagliflozin and statins may be considered in all situations where pro-inflammatory mechanisms are involved.

Observation of Collective Resonance Modes in a Chiral Spin Soliton Lattice with Tunable Magnon Dispersion.

A chiral spin soliton lattice (CSL), one of the representative systems of a magnetic superstructure, exhibits reconfigurability in periodicity over a macroscopic length scale. Such coherent and tunable characteristics of the CSL lead to an emergence of elementary excitation of the CSL as phononlike modes due to translational symmetry breaking and bring a controllability of the dispersion relation of the CSL phonon. Using a broadband microwave spectroscopy technique, we directly found that higher-order magnetic resonance modes appear in the CSL phase of a chiral helimagnet CrNb_{3}S_{6}, which is ascribed to the CSL phonon response. The resonance frequency of the CSL phonon can be tuned between 16 and 40 GHz in the vicinity of the critical field, where the CSL period alters rapidly. The frequency range of the CSL phonon is expected to extend over 100 GHz as extrapolated on the basis of the theoretical model. The present results indicate that chiral helimagnets could work as materials useful for broadband signal processing in the millimeter-wave band.

[Influence of the soft palate structure in patients with snoring and obstructive sleep apnea syndrome on the results of surgical treatment]. / Vliyanie osobennostei stroeniya myagkogo neba u patsientov s khrapom i sindromom obstruktivnogo apnoe sna na rezul'taty khirurgicheskogo lecheniya.

OBJECTIVE: To evaluate the variants of the anatomical structure of the soft palate in patients with snoring and obstructive sleep apnea (OSA) syndrome and their relationship with the severity of OSA syndrome. MATERIAL AND METHODS: The study included patients (n=71) with snoring and sleep apnea. For the purpose of treatment, patients underwent reconstructive interventions on the soft palate. All patients underwent a comprehensive examination, including the collection of complaints and anamnesis, examination of the upper respiratory tract, night respiratory monitoring. There are 5 types of soft palate structure, depending on which all patients are divided into 5 groups. The 1st and 2nd groups mainly included patients with simple snoring and mild OSA syndrome, the 3rd and 5th groups were evenly distributed with all degrees of severity of the same pathology, and the 4th group consisted mainly of patients with severe OSA syndrome. The procedure of the operation varied in different groups. 1 month after surgical treatment, there was a decrease in the anpoe/hypopnea index compared with preoperative values in patients of the 1st and 2nd groups by 71.9% and 76.2%, respectively, in patients of the 3rd group by 51.4%, in patients of the 5th group by 65.3%, in patients of the 4th group by 39.6%. CONCLUSIONS: The presented original classification of anatomical variants of the soft palate in patients with snoring and OSA syndrome makes it possible to determine the scope of intervention, predict the feasibility of surgery and can be recommended for practical use. Surgical treatment is indicated for types 1, 2, 3 and 5 of the structure of the soft palate. In patients with type 4, reconstructive operations on the soft palate do not lead to a satisfactory result and can only be used in combination with other methods of treatment.

[Modern H1 antihistamines in the treatment of patients with allergic rhinitis and comorbid acute respiratory infections]. / Sovremennye H1-antigistaminnye sredstva v terapii patsientov s allergicheskim rinitom i komorbidnymi ostrymi respiratornymi infektsiyami.

Patients with allergic rhinitis (AR) have a predisposition to frequent acute respiratory viral infections (ARVI). Inflammation of the mucous membrane of the nasal cavity and paranasal sinuses in such patients is more pronounced against the background of a combination of allergic and infectious inflammation. OBJECTIVE: To evaluate the effect of therapy using modern antihistamines on the condition and severity of symptoms in adult patients with exacerbation of AR caused by plant pollen (seasonal) (SAR) and the development of ARVI. MATERIAL AND METHODS: An observational study was conducted at the Department of Otorhinolaryngology of the Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation from April to August 2021. Included are patients of both sexes aged 18 to 65 years with a previously (at least 1 year ago) verified diagnosis of mild and moderate acute SAR in the acute stage, who sought medical help for ARVI. All patients were prescribed therapy with the inclusion of a drug belonging to the pharmacological group of antihistamines of the 2nd generation (a course of 14 days). In addition, patients received symptomatic ARVI therapy according to indications, including nasal decongestants (as needed), antipyretic and antitussive drugs. RESULTS: Based on the data obtained, it was possible to prove that the use of modern antihistamines in patients comorbid with AR and ARVI has a pronounced therapeutic effect. Theoritin provides a therapeutic effect at an early stage in relation to nasal and non-nasal symptoms of SAR/ARVI, and also quickly improves the quality of life of patients, which makes its use promising for the treatment of ARVI against the background of AR. The drug has an antihistamine activity comparable to cetirizine and surpasses it in its ability to suppress an allergic inflammatory reaction, for example on the skin, as well as in the duration of preservation of the antihistamine effect. CONCLUSION: The presented results indicate the effectiveness of theoritin and cetirizine in the treatment of patients with seasonal exacerbation of allergic rhinitis, comorbid for acute respiratory viral infections.

[Characteristics of student response to pandemic in cross-cultural context]. / Osobennosti reagirovaniya studentov pri pandemii v krosskul'tural'nom kontekste.

OBJECTIVE: Of the work is a cross-cultural analysis of the characteristics of student response in a pandemic situation. MATERIAL AND METHODS: The sample consisted of students of NSMU and the Kazakh National University. Al-Farabi in the amount of 37 people aged 20 to 23; The battery of psychological methods was compiled by Spielberger and Khanina; Mississippi Post-Traumatic Stress Disorder Scale (civil version) and PSM-25 Psychological Stress Scale. RESULTS: 52.7% of respondents showed an average level of stress, 47.3% - a low level, which indicates insufficient psychological adaptation to psychological stress. High rates of personal and situational anxiety were diagnosed in 67.57% of cases; the average level of reactive anxiety - in 29.73% of cases and personal - in 27.03% of respondents. The majority of respondents showed average levels of post-traumatic stress reactions (50%, n=37), while a low level of post-traumatic stress reactions occurs in 11 (14.87%) people, a low level - in 17 (22.97%) people and increased - in 9 (12.16%) people. Stress level indicators tend to have significant differences: the frequency of occurrence of average stress indicators in the sample of students from Kazakhstan is higher (75.6%) compared to Russian students (24.32%) (p<0.05).Adapting to changing academic workloads in a pandemic situation does not contribute to the psychological well-being of students, as evidenced by the results of diagnosing anxiety and post-traumatic stress reactions. The results obtained emphasize the importance of taking into account cultural factors in stressful situations. CONCLUSION: Cross-cultural differences in the level of emotional response of students in a pandemic situation were revealed.

[Comparative characteristics of the effectiveness of local therapy in acute tonsillopharyngitis]. / Sravnitel'naya kharakteristika effektivnosti mestnoi terapii pri ostrom tonzillofaringite.

Acute tonsillopharyngitis (ATP) is an infectious inflammation of the mucous membrane and lymphadenoid structures of the oropharynx. Sore throat, as the main symptom of ATP, is the most common reason for seeking outpatient medical care or self-medication. Topical therapy of sore throat in the treatment of non-streptococcal ATP is the most effective and safe. In the article, based on their own experience and literature data, the problem of treating patients with sore throat with ATP of non-streptococcal etiology is presented. At the Department of Otorhinolaryngology of the Evdokimov Moscow State Medical University conducted a study to study the clinical features of the course of ATP and improve the results of local treatment of patients with this pathology. In the course of the study, 75 people were examined, in whom subjective and objective symptoms were assessed. Our study showed that the use of the drug Doritricin demonstrated high efficacy in the treatment of patients with ATP, which contributed to an earlier regression of inflammatory-infiltrative changes in the pharynx, as well as a faster decrease in the level of pain syndrome according to the scores of the visual-analog pain scale.

Terahertz generation optimization in an OH1 nonlinear organic crystal pumped by a Cr:forsterite laser.

We present the results of experimental investigations of terahertz radiation generation conversion efficiency in an OH1 nonlinear organic crystal pumped by femtosecond laser pulses at 1240 nm wavelength. An influence of OH1 crystal thickness on the terahertz generation by optical rectification method was studied. It is shown that the optimal crystal thickness for the maximum conversion efficiency is 1 mm, which agrees with the previously made theoretical estimates.

[Ð ossibility of using European (HFA-PEFF) and American (H2FPEF) algorithms for diagnosing heart failure with preserved ejection fraction in Russian clinical practice].

This article focuses on the significance of a unified approach to diagnosing heart failure with preserved left ventricular ejection fraction (HFpEF). The key hemodynamic index of HFpEF is increased left ventricular filling pressure (LVFP) and its noninvasive marker, the E / e' value obtained by tissue Doppler echocardiography (EchoCG). The modern verified algorithms for HFpEF diagnosis, HFA-PEFF and Н2FPEF, mandatorily take into account the E / e' value. However, the routing use of these algorithms in the Russian practice may be complicated since even among "advanced" specialists who are interested in heart failure, 38% of the interviewed do not use or do not know how to use tissue Doppler EchoCG or the algorithm for diagnosing HFpEF with E / e'. In addition to the obvious way of overcoming this problem by equipping respective medical facilities with ultrasonic apparatuses with tissue Doppler EchoCG software and educating physicians, a possibility of using simplified HFA algorithm without the E / e' value is being considered. However, such approach will inevitably lead to erroneous estimation of the probability of HFpEF and, at the best, to underestimation of this probability with ensuing mistakes in diagnosis and treatment. Simplifying the HFA-PEFF and H2FPEF algorithms by omitting one or more parameters is possible but this requires a special investigation to develop a new rating scale and actually a new algorithm, which, in turn, will require a new validation.

[Focus ultrasound for cardiology practice. Russian consensus document].

This document is a consensus document of Russian Specialists in Heart Failure, Russian Society of Cardiology, Russian Association of Specialists in Ultrasound Diagnostics in Medicine and Russian Society for the Prevention of Noncommunicable Diseases. In the document a definition of focus ultrasound is stated and discussed when it can be used in cardiology practice in Russian Federation.

Free-carrier generation dynamics induced by ultrashort intense terahertz pulses in silicon.

We report the results of experimental studies and numerical simulation of the dynamics of the electron-hole pairs formation in silicon under the action of a two-period terahertz pulse with a maximum electric field strength of up to 23 MV/cm. It is shown that an inhomogeneous distribution of the charge carrier concentration over the depth of the silicon sample is formed, which persists for several microseconds. This inhomogeneity is formed due to a sharp increase in the rate of filling the conduction band with free carriers in the subsurface input layer of the silicon wafer, which occurs at a field strength above 15 MV/cm.

Data for determining the surface properties of carbon fiber in contact interaction with polymeric binders.

The data presented in this study are the supplementary materials related to the research paper "Determining the Surface Properties of Carbon Fiber in Contact Interaction with Polymeric Binders" (Voronina S.Yu. et al., 2018). The carbon fiber wettability properties before and after heat treatment and the coupling agent IR analysis results are presented. The coupling agent composition affects the fiber wettability and the capillary rise. The polymer binder impregnation rate drives the manufacturing process and the final composite quality. The data would be useful for researchers who study the interphase properties in composites and may help with determining the efficiency of applying certain polymers for wetting carbon fabrics.

[The use of diuretics in chronic heart failure. Position paper of the Russian Heart Failure Society].

The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.

[The role of diastolic transthoracic stress echocardiography with incremental workload in the evaluation of heart failure with preserved ejection fraction: indications, methodology, interpretation. Expert consensus developed under the auspices of the National Medical Research Center of Cardiology, Society of Experts in Heart Failure (SEHF), and Russian Association of Experts in Ultrasound Diagnosis in Medicine (REUDM)].

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is associated with certain difficulties since many patients with HFpEF have a slight left ventricular diastolic dysfunction and normal filling pressure at rest. Diagnosis of HFpEF is improved by using diastolic transthoracic stress-echocardiography with dosed exercise (or diastolic stress test), which allows detection of increased filling pressure during the exercise. The present expert consensus explains the requirement for using the diastolic stress test in diagnosing HFpEF from clinical and pathophysiological standpoints; defines indications for the test with a description of its methodological aspects; and addresses issues of using the test in special patient groups.