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With increasing demand for psychotherapy services, clinicians are carrying increasingly large caseloads (Bailey et al., 2020). As the number of new intakes exceeds the number of clinical hours available each week in some settings, psychotherapy is delivered on an attenuated schedule for returning clients (rather than the traditional weekly frequency); there is, however, little support for the efficacy of this practice. The present study explored the effect of session frequency on psychotherapy outcomes using a quasi-randomized controlled design. In a working university counseling center, we assigned therapists to either a treatment-as-usual (TAU) group (attenuated session frequency) or an experimental group (weekly session frequency). Clients were randomly assigned to a therapist in either condition. Using hierarchical linear modeling and survival analyses, we examined psychotherapy outcomes (measured by session-by-session Outcome Questionnaire 45 scores) for 1,322 clients (3,919 individual sessions). We found no differences between groups when examining the full sample, but also found limited fidelity in the experimental group. When identifying individuals who were seen weekly in at least the first three sessions after intake (sensitivity analysis), we found the following: (a) weekly therapy resulted in faster trajectories of change over time, (b) weekly therapy resulted in a greater likelihood of achieving recovery, and (c) weekly therapy resulted in a greater likelihood of achieving recovery sooner. We discuss the importance of including session frequency when considering the dose of therapy, as well as the implication that prioritizing weekly therapy may increase therapy efficacy and efficiency in routine practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The study was aimed at exploring the clinical value of a 14-zone lung ultrasound scoring (LUS) method in treating neonatal respiratory distress syndrome (NRDS) with pulmonary surfactant (PS) and determining the timing of mechanical ventilation (MV). In this study, 88 neonates with NRDS who received PS replacement therapy were selected. We applied a new 14-zone LUS method before and 12, 24, 48 and 72 h after PS treatment to explore the clinical value of assessing PS replacement therapy efficacy in NRDS. Additionally, 67 patients with NRDS under MV received LUS during extubation. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of LUS in the timing of extubation. LUS score was inversely associated with PS treatment. At 12 h after PS, only the 14-zone LUS method was significantly different (t = 4.08, p0.05) as compared with before PS, which was consistent with the change on chest x-ray (CXR); the other LUS methods did not differ (p0.05). The 14-zone LUS method exhibited better diagnostic performance for withdrawal time. A score of 41.0 points was used as the diagnostic threshold to predict the risk of withdrawal failure, with an area under the curve of 0.955, sensitivity of 92.4% and specificity of 93.8%. The new 14-zone LUS method improved scoring in the early efficacy of PS and had good diagnostic efficiency for timing the removal of MV in NRDS.

Patient-derived organoids are being considered as models that can help guide personalized therapy through in vitro anti-cancer drug response evaluation. However, attempts to quantify in vitro drug responses in organoids and compare them with responses in matched patients remain inadequate. In this study, we investigated whether drug responses of organoids correlate with clinical responses of matched patients and disease progression of patients. Organoids were established from 54 patients with colorectal cancer who (except for one patient) did not receive any form of therapy before, and tumor organoids were assessed through whole-exome sequencing. For comparisons of in vitro drug responses in matched patients, we developed an "organoid score" based on the variable anti-cancer treatment responses observed in organoids. Very interestingly, a higher organoid score was significantly correlated with a lower tumor regression rate after the standard-of-care treatment in matched patients. Additionally, we confirmed that patients with a higher organoid score (≥ 2.5) had poorer progression-free survival compared with those with a lower organoid score (< 2.5). Furthermore, to assess potential drug repurposing using an FDA-approved drug library, ten tumor organoids derived from patients with disease progression were applied to a simulation platform. Taken together, organoids and organoid scores can facilitate the prediction of anti-cancer therapy efficacy, and they can be used as a simulation model to determine the next therapeutic options through drug screening. Organoids will be an attractive platform to enable the implementation of personalized therapy for colorectal cancer patients.

Background and ObjectivesEndogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2–0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0–2.9]), increased triptan intake (OR 1.2 [1.1–1.4]), higher headache intensity (OR 1.4 [1.2–1.7]), less pain coping (mean difference −0.2 [−0.3 to −0.1]), more pronounced photophobia (OR 1.3 [1.2–1.4]) and phonophobia (OR 1.2 [1.1–1.4]), and less aura (OR 0.8 [0.6–1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.

The risks related to the COVID-19 are multi-faceted including but by far not restricted to the following: direct health risks by poorly understood effects of COVID-19 infection, overloaded capacities of healthcare units, restricted and slowed down care of patients with non-communicable disorders such as cancer, neurologic and cardiovascular pathologies, among others; social risks—restricted and broken social contacts, isolation, professional disruption, explosion of aggression in the society, violence in the familial environment; mental risks—loneliness, helplessness, defenceless, depressions; and economic risks—slowed down industrial productivity, broken delivery chains, unemployment, bankrupted SMEs, inflation, decreased capacity of the state to perform socially important programs and to support socio-economically weak subgroups in the population. Directly or indirectly, the above listed risks will get reflected in a healthcare occupation and workload which is a tremendous long-term challenge for the healthcare capacity and robustness. The article does not pretend to provide solutions for all kind of health risks. However, it aims to present the scientific evidence of great clinical utility for primary, secondary, and tertiary care to protect affected individuals in a cost-effective manner. To this end, due to pronounced antimicrobial, antioxidant, anti-inflammatory, and antiviral properties, naturally occurring plant substances are capable to protect affected individuals against COVID-19-associated life-threatening complications such as lung damage. Furthermore, they can be highly effective, if being applied to secondary and tertiary care of noncommunicable diseases under pandemic condition. Thus, the stratification of patients evaluating specific health conditions such as sleep quality, periodontitis, smoking, chronic inflammation and diseases, metabolic disorders and obesity, vascular dysfunction, and cancers would enable effective managemenet of COVID-19-associated complications in primary, secondary, and tertiary care in the context of predictive, preventive, and personalized medicine (3PM).

Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent. Herein, we aimed to prepare uniform PEGylated (lactic-co-glycolic acid) (PLGA) microcapsules (PB@(Fe3O4@PEG-PLGA) MCs) with superparamagnetic Fe3O4 nanoparticles embedded in the shell and Prussian blue (PB) NPs inbuilt in the cavity via a premix membrane emulsification (PME) method. On account of the eligible geometry and multiple load capacity, these MCs could be used as efficient multi-modality contrast agents to simultaneously enhance the contrasts of US, MR and PAT imaging. In-built PB NPs furnished the MCs with excellent photothermal conversion property and embedded Fe3O4 NPs endowed the magnetic location for fabrication of targeted drug delivery system. Notably, after further in-situ encapsulation of antitumor drug of DOX, (PB+DOX)@(Fe3O4@PEG-PLGA) MCs possessed more unique advantages on achieving near infrared (NIR)-responsive drug delivery and magnetic-guided chemo-photothermal synergistic osteosarcoma therapy. In vitro and in vivo studies revealed these biocompatible (PB+DOX)@(Fe3O4@PEG-PLGA) MCs could effectively target to the tumor tissue with superior therapeutic effect against the invasion of osteosarcoma and alleviation of osteolytic lesions, which will be developed as a smart platform integrating multi-modality imaging capabilities and synergistic effect with high therapy efficacy., Graphical abstract Schematic illustration of a theranostic agent of (PB+DOX)@(Fe3O4@PEG-PLGA) MCs towards multi-modality imaging, magnetic targeting ability and NIR-triggered chemo-photothermal osteosarcoma therapy.Image 1, Highlights • A facile and efficient premix membrane emulsification method to prepare multifunctional theranostic agents. • These MCs possess excellent US/MR/PAT multi-modality imaging performance. • These MCs achieve the synergistic therapeutic outcomes of chemotherapy and photothermal therapy in response to NIR stimuli. • A combined effect of magnetic targeting and chemo-photothermal osteosarcoma therapy with prominent anticancer efficacy.

Procyanidins (PCs), as the second most abundant natural phenolic compounds on earth, have gained much attention due to their various health promoting effects. However, the proven benefits of PCs ha...

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P

Wide usage of biologic disease-modifying anti-rheumatic drugs (DMARDs) biosimilars in clinical practice has greatly increased the availability of biologic therapy for rheumatic patients. Nevertheless, not only economic expediency but efficacy and safety are the key principals of any treatment including biologic DMARDs. Objective . To investigate the efficacy and safety of switching from the original rituximab (MabThera®, “F. Hoffmann-La Roche Ltd.”, Switzerland) to its biosimilar (Acellbia®, “BIOCAD”, Russia) by non-medical reasons in rheumatoid arthritis patients. Subjects and methods . 40 rheumatoid arthritis patients on basic therapy who had taken at least one course of original rituximab (MabThera®) 1000 mg twice in 2 weeks more than 6 months ago were included. They were switched to equal-dose biosimilar (Acellbia®) by non-medical reasons and were observed throughout the year. At 12, 24 weeks and one year after switching dynamics of the next parameters were evaluated: pain level according to visual analogue scale (VAS), tender joint count (TJC), swollen joint count (SJC), acute inflammatory and immunological markers, disease activity score (DAS28) calculated using erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP), health assessment questionnaire (HAQ) index and safety profile. Results . All the data are presented as median of indicator in the moment of measurement after switching therapy (Meperiod). In 12-week period TJC [(Me]_0=9.50, Me_12=6.0, p< 0.01) and SJC (Me_0=2,0, Me_12=1,0, p

Background. The study of psoriasis biological therapy aspects in children has certain topicality due to the small number and disunity of individual observations and the lack of special registers for pediatric patients.Objective. Our aim was to study ustekinumab efficacy and safety in children with plaque (PP), erythrodermic (EP) and palmoplanar (PPP) forms of psoriasis.Methods. The analysis of ustekinumab efficacy and safety has been carrying out for 1 year. The evaluation of therapy efficacy was based on definition of improvement of PASI scores (PASI 75, PASI 90 and PASI 100) on the 16th, 28th, 40th and 52nd weeks of follow-up and children's dermatology life quality index (CDLQI). Ustekinumab therapy safety analysis was based on registration and evaluation of adverse effects. Results. The study included 67 children with PP, EP and PPP aged 12 to 18 years. PP group results: the PASI 75 response at the 52nd week of therapy was observed in 35 children (100%), PASI 90 — in 33 (94%), PASI 100 — in 30 (86%). EP group results: 10 patients (56%) have reached PASI 75 on the 16th week, while none of patients have improved to PASI 90 and PASI 100 scores. The PASI 75 response at the 52nd week of therapy was observed in 18 children (100%), PASI 90 — in 17 (94%), PASI 100 — in 7 (39%). Only 1 patient (7%) with PPP has showed the score decrease to PASI 75 on the 16th week. Adverse effects were reported in 2 patients.Conclusion. Ustekinumab is the effective and safe treatment for moderate and severe forms of PP and EP in children, and it can also be considered as one of the alternative methods for PPP treatment in pediatrics.

Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [18F]FDG-PET and bioluminescence images for complementary detection of tumor viability. Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [111In]3 for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [111In]3-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatment, p = 0.044) and decreased [18F]FDGuptake (3.02 ± 0.51%ID/g after saline treatment, 1.79 ± 0.11%ID/g after doxorubicin treatment, p = 0.040), indicating therapy efficacy. Moreover, we detected increased [111In]3-uptake and tumor necrosis in more rapidly growing EMT6 tumors. Conclusions: Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging.

Fluorine-19 (19F) magnetic resonance (MR) molecular imaging is a promising noninvasive and quantitative molecular imaging approach with intensive research due to the high sensitivity and low endogenous background signal of the 19F atom in vivo. Perfluorocarbons (PFCs) have been used as blood substitutes since 1970s. More recently, a variety of PFC nanoparticles have been designed for the detection and imaging of physiological and pathological changes. These molecular imaging probes have been developed to label cells, target specific epitopes in tumors, monitor the prognosis and therapy efficacy and quantitate characterization of tumors and changes in tumor microenvironment noninvasively, therefore, significantly improving the prognosis and therapy efficacy. Herein, we discuss the recent development and applications of 19F MR techniques with PFC nanoparticles in biomedicine, with particular emphasis on ligand-targeted and quantitative 19F MR imaging approaches for tumor detection, oxygenation measurement, smart stimulus response and therapy efficacy monitoring, et al.

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Background: Chronic urticarial patients suffer from recurrent wheals which are severely itching for more than 6 weeks. The symptoms are more in auto-reactive urticaria (arCU) where auto-antibodies in blood flares-up the condition. Autologus serum skin test (ASST) is regarded of a great value in the primary assessment of patients' auto reactivity. Autologous serum therapy (AST) is a promising treatment modality for CSU patients with positive ASST by inducing desensitization to the pro-inflammatory mediators expressed in their blood. Aim of the work: Improvement of chronic urticarial symptoms with a therapeutic option that is cheaper, safer and less risky than standard treatment options. Patients and methods: Single-blind randomized controlled clinical trial study was done on 48 CU patients (+ASST) and randomized into 2 groups; 24patients in cases group on anti-histamines will receive 9 weekly injections of AST and another 24 patients in control group will receive antihistamines alone for 9 weeks. We compared the urticarial activity score-7 of both groups at baseline, fourth week, ninth week of treatment and at twelfth week of follow up after treatment to evaluate the efficacy of addition of AST to conventional treatment with antihistamines. Results: The mean of UAS-7 was decreased in both treatment groups throughout the twelve weeks of treatment and follow up but the UAS-7 showed significant decrease in the cases group more than that of the control group from the fourth week onwards as P< 0.05. Conclusion: In patients with arCU, AST is a useful adjunct to antihistamines which improves the urticarial symptoms.

Oncolytic virus immunotherapy is rapidly gaining interest in the field of immunotherapy against cancer. The minimal toxicity upon treatment and the dual activity of direct oncolysis and immune activation make therapy with oncolytic viruses (OVs) an interesting treatment modality. The safety and efficacy of several OVs have been assessed in clinical trials and, so far, the Food and Drug Administration (FDA) has approved one OV. Unfortunately, most treatments with OVs have shown suboptimal responses in clinical trials, while they appeared more promising in preclinical studies, with tumours reducing after immune cell influx. In several clinical trials with OVs, parameters such as virus replication, virus-specific antibodies, systemic immune responses, immune cell influx into tumours and tumour-specific antibodies have been studied as predictors or correlates of therapy efficacy. In this review, these studies are summarized to improve our understanding of the determinants of the efficacy of OV therapies in humans and to provide insights for future developments in the viro-immunotherapy treatment field.

The external surfaces of two-dimensional (2D) nanoarchitectures are easily functionalized to confer attractive and unique properties in nanomedicine. On the basis of the high surface area for desired drug-loading capacity, efficient cell uptake, attractive biocompatibility, and established chemical functionalization routes, layered nanoarchitectures as hosts are significantly exploited to function as intelligent drug delivery platforms for chemotherapy and combined therapies. Additionally, functionalization on the surfaces of 2D nanomaterials is subsequently integrated with stimuli-responsive characteristics and, thus, 2D hybrid-based drug release platforms equipped with the characteristics of triggered cargo release contribute to improving therapy efficacy with simultaneously diminished side effects. Herein, we briefly introduce the classification of 2D nanomaterials integrated with chemical functionalization, with a complete list of responsive endogenous and exogenous triggers. Comparisons between diverse 2D nanoarchitectures are highlighted and proposed horizons are also presented for addressing current drawbacks that are affecting their potential clinical applications.

Ex vivo X-ray phase contrast tomography of amyotrophic lateral sclerosis of a SOD1G93A mouse model is presented. Quantification of neuronal and vascular alteration in the central nervous system is described., Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.

The aim - to study the efficacy and safety of favipiravir (Areplivir) in patients with novel coronavirus infection (COVID-19) in comparison with the recommended standard therapy Material and methods 200 men and women with COVID-19 between the ages of 18 and 80 were randomized in the study The main group consisted of patients receiving treatment with favipiravir, in the comparison group, patients were prescribed etiotropic therapy in accordance with the current version of the Temporary guidelines of the Ministry of Health of Russia "Prevention, diagnosis and treatment of coronavirus infection (COVID-19)" The efficacy and safety of therapy was determined based on the assessment of clinical improvement according to the WHO Categorical Scale of Clinical Improvement, clinical and laboratory data, the results of CT scan of the chest organs and the clearance of the SARS-CoV-2 virus The frequency and nature of the occurrence of adverse events, the need for invasive and non-invasive oxygen support, and the frequency of deaths were also evaluated Results The performed comparative analysis demonstrated a significant advantage of favipiravir therapy compared with standard therapy in terms of the rate of improvement in clinical status (on average by 4 days), the speed and frequency of recovery on the 10th day of therapy (no clinical signs of the disease in the study and control groups were observed in 44 and 10% of patients, respectively), the frequency of achieving the viral clearance on the 10th day of therapy (98 and 80% in the study and control groups, respectively) (p=0 00003) Favipiravir therapy was accompanied by a significant improvement in lung condition according to CT data, improved laboratory parameters and normalization of oxygen saturation levels Favipiravir therapy was characterized by a favorable safety profile In the main group, no aggravation of the course of the disease or serious adverse events related to the drug were recorded Conclusions The use of favipiravir for the treatment of infection caused by the SARS-CoV-2 can shorten the period before the onset of clinical improvement by an average of 4 days compared with standard therapy, improve the lung condition according to CT and the viral clearance in more than 90% patients, which contributes to a faster recovery Favipiravir therapy is characterized by a favorable safety profile and good tolerability The overall incidence of adverse events in the favipiravir group was comparable to that observed with standard therapy The selected therapy regimen can be considered clinically justified, the course of therapy is necessary and sufficient to achieve the required therapy efficacy Timely initiation of therapy with favipiravir (Areplivir) improves the prognosis of the disease and reduces the global socio-economic burden of the current pandemic Цель исследования - изучить эффективность и безопасность применения препарата фавипиравир (Арепливир) у больных COVID-19 по сравнению с рекомендованной стандартной терапией Материал и методы В исследование были рандомизированы 200 мужчин и женщин в возрасте от 18 до 80 лет с COVID-19 Основную группу составили пациенты, получавшие лечение препаратом фавипиравир, в группе сравнения пациентам назначали этиотропную терапию в соответствии с актуальной версией Временных методических рекомендаций Минздрава России по профилактике, диагностике и лечению новой коронавирусной инфекции (COVID-19) Эффективность и безопасность терапии определяли на основании оценки клинического улучшения по Категориальной шкале клинического улучшения Всемирной организации здравоохранения, клинико-лабораторных данных, результатов компьютерной томографии (КТ) органов грудной клетки и показателей элиминации вируса SARS-CoV-2 Также оценивали частоту и характер нежелательных явлений, потребность в применении инвазивной и неинвазивной кислородной поддержки и частоту наступления смертельных случаев Результаты Проведенный сравнительный анализ продемонстрировал значимые преимущества терапии фавипиравиром по сравнению со стандартной терапией в отношении скорости улучшения клинического статуса (в среднем на 4 дня), сроков выздоровления и доли выздоровевших на 10-й день терапии (отсутствие клинических признаков заболевания в основной и контрольной группах наблюдалось у 44 и 10% пациентов соответственно), частоты достижения элиминации вируса на 10-й день терапии (98 и 80% в основной и контрольной группах соответственно) (р=0,00003) Терапия фавипиравиром сопровождалась значимым улучшением состояния легких по данным КТ, улучшением лабораторных показателей и нормализацией уровня сатурации Терапия фавипиравиром характеризовалась благоприятным профилем безопасности В основной группе не зарегистрировано отягощения течения заболевания, серьезных нежелательных явлений, связанных с приемом препарата Заключение Применение фавипиравира для лечения инфекции, вызванной коронавирусом SARS-CoV-2, позволяет сократить период до наступления клинического улучшения в среднем на 4 дня по сравнению со стандартной терапией, достичь улучшения состояния легких по данным КТ и элиминации вируса более чем у 90% пациентов, что способствует ускорению выздоровления Терапия фавипиравиром характеризуется благоприятным профилем безопасности и хорошей переносимостью Общая частота нежелательных явлений в группе, получавшей фавипиравир, сопоставима с показателями на фоне стандартной терапии Выбранная схема терапии может считаться клинически обоснованной, курс терапии является необходимым и достаточным для достижения требуемой эффективности терапии Своевременное начало терапии фавипиравиром (Арепливир) способствует улучшению прогноза заболевания и снижению глобального социально-экономического бремени текущей пандемии

Purpose: Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (MBC) is an important consideration for subsequent use in clinical practice. Unfortunately, such subgroup analyses often are exploratory and rarely statistically adequately powered and may thus be misleading. This analysis aimed to explore a potentially different treatment response to i.v. therapies between visceral and non-visceral MBC. Methods: In a systematic literature analysis (PubMed) comprising phase III registration studies for MBC from 1994 to 2014, differences in outcome were evaluated regarding progression-free survival, time to progression, overall survival (OS), and visceral versus non-visceral disease. The impact of HER2 and hormone receptor status was also considered. A total of 16 studies comprising 13,083 patients were selected by considering the information given in the medical product’s professional information and the decision of the US Food and Drug Administration or the European Medicine Agency for approval of the respective therapeutic agents now used in the treatment of MBC. Results: No statistically significant differences regarding treatment response and therapy benefit were found in MBC patients with visceral versus non-visceral metastases based on reported hazard ratios and confidence intervals in registration trials. Interesting but nonsignificant differences were found regarding a distinct therapy benefit regarding different metastasis locations in 4 studies. Conclusion: For targeted i.v. therapies based on biomarker selection, there is a trend – although not significant – toward a benefit (OS) from combination therapies favoring visceral disease. However, at the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in MBC.

The role of gut microbiota in the development of various tumors has been a rising topic of public interest, and in recent years, many studies have reported a close relationship between microbial groups and tumor development. Gut microbiota play a role in host metabolism, and the positive and negative alterations of these microbiota have an effect on tumor treatment. The microbiota directly promote, eliminate, and coordinate the efficacy of chemotherapy drugs and the toxicity of adjuvant drugs, and enhance the ability of patients to respond to tumors in adjuvant immunotherapy. In this review, we outline the significance of gut microbiota in tumor development, reveal its impacts on chemotherapy and immunotherapy, and discover various potential mechanisms whereby they influence tumor treatment. This review demonstrates the importance of intestinal microbiota-related research for clinical tumor treatment and provides additional strategy for clinical assistance in cancer treatment.

Cell membrane-camouflaged nanoparticles are drawing increasing attention because their surfaces retain the natural functionalities of the cell plasma membranes, making them a unique class of biomimetic materials combining natural and synthetic components. Modifying the cell membranes or combining the functions of different types of membranes enhances their functionality. Herein, we prepared platelet and tumor cell membrane camouflaged antitumor nanoparticles. The effects of β-mangostin-loaded nanoparticles on the target and its anticancer action in glioma were measured in vitro and in vivo. Multifunctional nanoparticles were manufactured with platelet–C6 hybrid biomimetic coating (PCM), lactic-co-glycolic acid (PLGA), and β-mangostin. PCM increased the proportion of active drug targeting in C6 and immune escape characteristics in THP-1 cells, thus enhancing the cytotoxicity of β-PCNPs. The β-PCNPs were comprehensively characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting ability and induced apoptosis of C6 cells in vitro. Mice experiments with intravenous administration of the drug revealed that the β-PCNP platform enhanced the tumor targeting capability and exhibited excellent chemotherapy with high inhibition rate of glioma tumor growth in vivo. The mice in the β-PCNP group had a markedly prolonged circulation lifetime and exhibited better outcome than those in the β-NP group. These results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.

The paper presents the results of the Osteoarthritis (OA) Expert Council held on September 8, 2019, which was attended by Russian and foreign specialists. The experts considered pharmacological treatment options for OA. The expert meeting resolution states that the treatment of patients with OA should be based on an individual assessment of the patient and on a modern evidence base of therapy efficacy.Treatment of patients with OA is based on the principles of evidence-based medicine that requires an integrated approach and the need of SYSADOAs prescription. Combined drugs with therapeutic dosages of chondroitin sulfate and glucosamine in the early stages of the disease are available as basic agents. The place of paracetamol in the anesthetic therapy algorithm in OA needs to be clarified. It is also noted that when choosing nonsteroidal anti-inflammatory drugs for OA treatment, it is important to take into account individual patient characteristics and the presence of comorbidities.

Background Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-β-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC. Methods We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated. Results The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment. Conclusion Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

The number of patients with diabetes mellitus worldwide is increasing with geometric progression, and thus there is an increase in the percentage of related complications. Diabetic foot syndrome is one of the most serious chronic complications that often results in early disability, long stretches of hospitalization, mounting expenses, and an amputated limb. At present, vacuum therapy in the treatment of purulent necrotic lesions of diabetic foot syndrome is being successfully used in medical practice. The aim of our study was to search and verify for indirect methods of express control of the vacuum therapy efficacy. Based on applying our patented local treatment technique, which includes the negative pressure wound therapy, we determined the pH dynamic changes and the monitored the microbiological climate of wounds. According to the results obtained, the high efficacy of the proposed technique has been found out and statistically confirmed. Starting from the 4th day of applying this technique, the main group demonstrated induced, significantly accelerated pH changes in the wounds that create the conditions for early growth of granulation tissue; the reduction of microbial load in the wound indirectly enhances these processes that were found out twice as slow in the comparison group. Therefore, the contact pH monitoring of wound is quite helpful for checking the therapy efficacy as well as for predicting the course of wound healing. Our study has confirmed its effectiveness in pH changing that positively affects the course of wound healing. Applying negative pressure wound therapy as an integral component of combined treatment of purulent necrotic lesions of diabetic foot syndrome allows medical practitioners to accelerate pH changes to reach their optimum values and considerably promotes the beginning of the second phase of wound healing. The study has also proven the enhanced elimination of bacterial agents from the wound by using this technique that also promotes the early activation of the phase 2 and significantly reduces the percentage of suppurative complications in the future.