A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors.

BACKGROUND: This study aimed to evaluate the safety, pharmacokinetics (PKs), and preliminary activity of LY3405105, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), in patients with advanced solid tumors. MATERIALS AND METHODS: LY3405105 monotherapy was given once daily (QD; part A1) or thrice weekly (TIW; part A2) starting at 1 and 2 mg orally, respectively, and escalated per a Bayesian design in adult patients. The primary endpoint was safety, and secondary endpoints included PKs and antitumor activity. RESULTS: Fifty-four patients were enrolled: 43 in part A1 and 11 in part A2. Seven patients had dose-limiting toxicities, all in part A1 (45 mg: n = 3; 35 mg: n = 3; 25 mg: n = 1). Thirty-five patients (64.8%) reported at least one treatment-related adverse event (TRAE). TRAEs (≥10%) were diarrhea, nausea, fatigue, vomiting, abdominal pain, anemia, asthenia, and decreased platelet count. QD dosing showed sustained exposure with less peak-trough fluctuation compared to TIW dosing. Median time to maximum concentration was 1-2 hours and half-life was 15-19 hours. CDK7-target occupancy in skin and peripheral blood on day 15 was dose-dependent and reached near maximal occupancy of 75% at ≥15 mg QD. The maximum tolerated dose (MTD) was 20 mg QD. Twelve patients in part A1 (27.9%) and 5 patients in part A2 (45.5%) had a best overall response of stable disease. No complete response or partial response was observed. CONCLUSION: The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development. CLINICALTRIALS.GOV IDENTIFIER: NCT03770494.

[Targeted use of comprehensive geriatric assessment tools in cardiology. Part I (literature review).]

The purpose of this review is to demonstrate the importance of using a comprehensive geriatric examination in cardiology, including geriatric aspects of the management of this patient population. Until now, the Russian Federation has completely lacked a geriatric approach to the management of cardiological patients, which provides for consideration of international experience in this survey. The curation of elderly and elderly patients is complicated by the presence of geriatric syndromes and age-associated diseases leading to deterioration of quality of life, repeated hospitalizations, disability and risk of death. The leading geriatric syndrome in geriatric practice is senile asthenia and multiple comorbid polymorbid pathologies of the geriatric patient. A patient admitted to an acute care hospital with a history of cardiovascular comorbid pathology is primarily viewed as a patient at high risk for cardiovascular complications, omitting the risk of adverse outcomes, including loss of independence and impaired functional status. The following literature review demonstrates the importance of defining senile asthenia outside of the geriatrician's office, justifying the need for advanced training for cardiologists in geriatrics.

Case 311: Generalized Lymphatic Anomaly.

HISTORY: A 14-year-old boy presented with asthenia, low back pain, and abdominal distention. The onset of symptoms was slow and progressive over a few months. The patient had no contributing past medical history. At physical examination, all vital signs were normal. Only pallor and positive fluid wave test results were noted; there was no lower limb edema, mucocutaneous lesions, or palpable lymph node enlargement. Laboratory work-up revealed a decreased hemoglobin concentration of 9.3 g/dL (normal range, 12-16 g/dL) and a decreased hematocrit level of 29.8% (normal range, 37%-45%), but all other laboratory values were normal. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed.

Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics.

BACKGROUND: Brain 18F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics. METHODS: We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics. RESULTS: Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r = - 0.44, p = 0.02) and with the duration of symptoms (r = - 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters. CONCLUSION: Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.

Solar radiation leads to increased collagenase gene expression (MMP1) in HERDA (Hereditary equine regional dermal asthenia) affected horses and may explain the typical dorsal distribution of their lesions.

BACKGROUND: Hereditary equine regional dermal asthenia (HERDA) is a genetic disease that alters collagen biosynthesis. Affected horses exhibit fragile, hyperextensible skin, especially over the dorsal region. Although ultraviolet (UV) radiation seems to contribute to the regional distribution of lesions and worsening of clinical signs, the molecular mechanisms involved are largely unknown. OBJECTIVES: To evaluate the effect of solar radiation on matrix metalloproteinase MMP1, MMP8 and MMP13 gene expression in the dorsal and ventral skin of HERDA-affected and HERDA-unaffected horses [wild-type (WT) horses]. ANIMALS: Six HERDA-affected and six unaffected Quarter horses (WT) were paired according to age, sex and coat colour. MATERIALS AND METHODS: Horses were submitted to 30 day sunlight restriction, followed by 15 day sunlight exposure. Dorsal and ventral skin biopsies were obtained at six sampling times over 45 days. The expression of MMP1, MMP8 and MMP13 genes was measured by quantitative PCR. RESULTS: Although solar radiation modulated MMP1, MMP8 and MMP13 expression, the effects were more pronounced on MMP1. Sun exposure for three days significantly upregulated MMP1 in the dorsal region when compared to the ventral skin in both unaffected and HERDA-affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that solar irradiation leads to upregulation of skin collagenase genes particularly MMP1 in the dorsal, sun-exposed skin of horses. Furthermore, this was more marked in HERDA-affected horses. The increased activity of collagenases on the disorganised collagen present in HERDA affected horses would explain why UV radiation leads to deterioration of clinical signs in affected individuals.

[The role of routine clinical examination in the selection of patients for screening of geriatric syndromes.]

The great complexity of complex geriatric assessment makes it relevant to search for methods that facilitate the selection of patients who really need it. The article presents the results of studying the possibility of using a routine clinical examination to select elderly cardiological patients with an increased risk of senile asthenia. The study involved 52 elderly patients with heart and vascular pathology. All of them underwent a generally accepted clinical and laboratory-instrumental examination, the results of which were compared with the data of the questionnaire «Age is not a hindrance¼. To identify the relationships between the parameters of clinical and geriatric status, analysis of variance and correlation analysis were used; summary frequency tables were built and analyzed. The significance threshold (p-value) was less than 5% (p<0,05). As a result of the study, it was found that the general condition of patients differing from satisfactory, complaints of shortness of breath, headaches, the presence of peripheral edema, lack of pulse on the dorsalis pedis arteries and posterior tibial arteries indicate an increased likelihood of senile asthenia in the subjects (p<0.05).

[Frequency of selected chronic noncommunicable diseases in older patients with senile asthenia syndrome.]

An important area of medical and social research is prospective studies of a cohort of older patients with chronic non-communicable diseases aimed at studying the level of mortality, taking into account the presence/absence of senile asthenia syndrome. A prospective clinical and epidemiological study was conducted on 1 261 people aged 80 years and older receiving medical care on an outpatient basis. Three groups of patients were formed: without senile asthenia syndrome (7,6%), in a state of pre-asthenia (23,5%), with senile asthenia (68,9%). After a calendar year, an analysis was made of the causes of death of respondents in all three groups. A high statistically significant incidence of chronic diseases in patients with senile asthenia syndrome compared with those without signs of this syndrome was noted in arterial hypertension, chronic heart failure, osteoarthritis, age-related macular degeneration, chronic kidney disease, dementia, cancer, anemia, uncomplicated diabetes mellitus. In the structure of causes of death in patients aged 80 years and older, diseases of the circulatory system, nervous system, neoplasms, liver diseases, and diabetes mellitus predominated. The odds ratio of the risk of dying within a year in patients without frailty syndrome is 0,32 (compared to patients with frailty, in which the risk is taken as 1).

[Pharmacoepidemiological analysis of antihypertensive therapy in older age groups with senile asthenia syndrome].

AIM: To conduct a pharmacoepidemiological study to determine the characteristics of antihypertensive therapy in older patients with senile asthenia syndrome (SSA) and compliance of this therapy with modern clinical recommendations. MATERIALS AND METHODS: The study included 146 patients diagnosed with stage I-III hypertension who underwent inpatient treatment in the therapeutic department of the Krasnoyarsk Regional Hospital for War Veterans, the subjects were divided into two groups. The first group included 55 elderly patients (WHO, 2012) with hypertension and SSA. The second group included 35 elderly patients (WHO, 2012) with hypertension and SSA. The comparison group consisted of 56 patients aged 60 to 84 years with hypertension without SSA. Evaluation of the pharmacotherapy was carried out based on extracts from the medical histories of inpatient patients. RESULTS: The most commonly taken groups of antihypertensive drugs in patients of older age groups with hypertension and SSA according to the study are diuretics and ß-blockers. Diuretics were taken by 88.6% of elderly patients and 83.6% of senile patients. The main combinations of antihypertensive drugs in patients with hypertension and SSA were: a two-component scheme of combination of an ACE inhibitor and a diuretic, a three-component scheme of combination of an ACE inhibitor, a ß-blocker and a diuretic, four-component schemes of combination of an ACE inhibitor, a ß-blocker, a calcium channel blocker and a diuretic, as well as a combination of an angiotensin II receptor blocker, a ß-blocker, calcium channel blocker and diuretic with combined medications. CONCLUSION: The prescribed antihypertensive therapy in patients of older age groups with hypertension and SSA in most cases is represented by a combination of several drugs. Many patients take three-component antihypertensive therapy regimens. There were no statistically significant differences between patients of older age groups with hypertension and SSA, as well as patients of older age groups with hypertension without SSA. Therefore, it can be concluded that the presence of senile asthenia syndrome does not affect the tactics of treatment of hypertension and regardless of the presence or presence of SSA, patients receive the same hypotensive therapy, which contradicts existing clinical guidelines.

[The structure of post/long COVID fatigue syndrome. Prospects for correction].

AIM: To study the features of post-COVID asthenic syndrome and evaluate the effectiveness of the drug containing the succinic acid complex with trimethylhydrazinium in its treatment. MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the efficacy of sequential therapy with BRAINMAX® included 160 patients with a history of coronavirus infection within 12 to 16 weeks (not more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. Testing was performed on the following scores: VAS for headache score, MFI-20 asthenia score, PSQI test, FAS-10 fatigue score, DHI dizziness score, MoCA cognitive impairment score, Beck anxiety score, vegetative index of Kerdo. RESULTS: PSQI questionnaire showed significant improvement in sleep quality in the study group: by -2.5 points [-4; -1] (p<0.001); there was a more pronounced significant decrease in the MFI-20 score of -19.5 points [-27; -11] (p<0.001); a significant decrease in the FAS-10 fatigue score by -9 [-13.5; -4] points (p<0.001); DHI dizziness score showed a decrease by -6 [-12; 0] points in the BRAINMAX® group (p=0.001); the score of Beck anxiety and depression scale decreased by -5 [-11; -2] points (p<0.001). Multiple linear regression data showed a significant increase of 0.56 (p=0.02) in the MoCA score. CONCLUSION: Our study convincingly showed the effectiveness of therapy with BRAINMAX® in a wide range of symptoms in patients with the post-COVID syndrome.

[Long-term consequences of COVID-19 in patients with functional bowel disorders, rehabilitation prospective of microbiocenosis-oriented therapy].

AIM: To analyze long-term consequences of the new coronavirus infection and rehabilitation prospective of microbiocenosis-oriented therapy in patients with functional bowel disorders. MATERIALS AND METHODS: The study enrolled 100 consecutive patients with various types of functional bowel disorders with recurrence of symptoms after the new coronavirus infection. The severity of abdominal pain was evaluated in points, and bowel movement disorders were assessed using the Bristol stool scale. A questionnaire was used as part of an in-depth clinical examination for COVID-19 survivors to identify the clinical symptoms typical for the post-COVID syndrome. The Hospital Anxiety and Depression Scale was used to identify and assess the severity of depression and anxiety, and the Asthenic State Scale was used to diagnose the asthenia. RESULTS: All patients in the study subjectively linked the recurrence of bowel disorders with the new coronavirus infection. The most common bowel disorder was irritable bowel syndrome with diarrhea. A distinctive feature of exacerbations of intestinal symptoms in the post-COVID period is their association with depression/anxiety and asthenic states. The addition of Zakofalk® metaprebiotic to the treatment regimen was associated with significant regression of abdominal pain and normalization of bowel movement, an improvement of asthenia, anxiety, and depression. CONCLUSION: The addition of Zakofalk® to treatment regimens for exacerbations of functional bowel disorders after the new coronavirus infection significantly improves the effectiveness of therapy.

[Surgical management of primary hyperparathyroidism]. / Prise en charge chirurgicale de l'hyperparathyroïdie primaire.

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia due to inappropriate parathyroid hormone (PTH) secretion mostly caused by a single adenoma. Clinical manifestations vary and include bone loss (osteopenia, osteoporosis), kidney stones, asthenia and psychiatric disorders. In 80 % of cases PHPT is asymptomatic. Secondary causes of elevated PTH such as renal insufficiency and/or vitamin D deficiency should be excluded, and 24-hour calciuria should be measured to rule out familial hyocalciuric hypercalcemia. Surgery requires radiological tests: a cervical ultrasound to exclude concomitant thyroid pathology and a functional examination (Sestamibi scintigraphy or F-choline PET scan). Management should be discussed in a multidisciplinary team. Treatment is surgical and can also be offered to asymptomatic patients.

L'hyperparathyroïdie primaire (HPTP) est caractérisée par une hypercalcémie causée par une sécrétion inappropriée de parathormone (PTH) due, dans la majorité des cas, à un adénome parathyroïdien unique. Les manifestations cliniques sont variées, comme la perte osseuse (ostéopénie, ostéoporose), les calculs rénaux, l'asthénie et les troubles psychiatriques. Dans 80 % des cas, l'HPTP est asymptomatique. Il faut exclure une cause secondaire d'élévation de la PTH sur une insuffisance rénale ou un déficit en vitamine D et doser la calciurie sur 24 heures pour exclure une hypercalcémie hypocalciurique familiale. La chirurgie nécessite des examens de radiologie au préalable : un ultrason cervical pour exclure une pathologie thyroïdienne concomitante et un examen fonctionnel (scintigraphie au Sestamibi ou PET-scan à la F-choline). Il est important de discuter de la prise en charge de façon multidisciplinaire. Le traitement curatif est chirurgical et peut aussi être proposé aux patients asymptomatiques.

[Concepts of modern gerontology and geriatrics and the role of nutrition in their achievement].

Many factors take part in increasing the healthy period of life - the quality of the environment, drinking water, psychological attitudes in society, dietary patterns, comfort of living, quality of housing, economic relations in the state and society, the degree of landscaping and much more. Collectively, the factors that lead to a healthier and longer life are called the environment that promotes longevity. The scientific study of such an environment, changing everyday life in terms of its quality related to health and increasing duration, is the newest trend in anti-aging medicine. Individual viability (intrinsic capacity) is one of the 4 concepts of geriatrics. The main concept is senile asthenia, the second is premature aging, the third is age viability, which is a psychological state of aging. It seems promising to study the effect of nutrition on individual vitality and longevity. Objective - to study the influence of nutrition on the aging process, to develop further preventive programs based on the data obtained. Methods. Search for literature on nutrition and age problems was held in the databases of RSCI, PubMed, Google Scholar by keywords: aging, ageism, nutrition, individual viability, age-related changes, resilience diet, age-related viability, senile asthenia, domain approach, age. Results. Domain-based assessment is a modern diagnosticis of the condition of people of older age groups, which forms the basis for the development of gerontological preventive programs, in which nutrition plays an important role. Modern studies indicate that the transition in nutrition from «Western¼ patterns to diets with a high content of plant products, as well as fish, vegetable protein (nuts), reduced salt content prevents the development of complications of age-associated diseases by the mechanism of reducing inflammation and hyperinsulinemia, replenishing micronutrient deficiency. Conclusion. Many studies have confirmed the relationship between compliance with optimal nutrition and longevity, as well as a reduced risk of early development of ageassociated diseases. Further research in the field of gerontology will help in the future to develop a comprehensive system of measures aimed at increasing life expectancy and increasing individual viability.

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States.

BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. METHODS: This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. RESULTS: Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0-1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3-4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). CONCLUSIONS: This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.

Clinical manifestations, treatment options, and comorbidities in COVID-19 relapse patients: A systematic review.

INTRODUCTION: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients. MATERIALS AND METHODS: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR. RESULTS: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died. CONCLUSION: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.

Predictions for Three-Month Postoperative Vocal Recovery after Thyroid Surgery from Spectrograms with Deep Neural Network.

Despite the lack of findings in laryngeal endoscopy, it is common for patients to undergo vocal problems after thyroid surgery. This study aimed to predict the recovery of the patient's voice after 3 months from preoperative and postoperative voice spectrograms. We retrospectively collected voice and the GRBAS score from 114 patients undergoing surgery with thyroid cancer. The data for each patient were taken from three points in time: preoperative, and 2 weeks and 3 months postoperative. Using the pretrained model to predict GRBAS as the backbone, the preoperative and 2-weeks-postoperative voice spectrogram were trained for the EfficientNet architecture deep-learning model with long short-term memory (LSTM) to predict the voice at 3 months postoperation. The correlation analysis of the predicted results for the grade, breathiness, and asthenia scores were 0.741, 0.766, and 0.433, respectively. Based on the scaled prediction results, the area under the receiver operating characteristic curve for the binarized grade, breathiness, and asthenia were 0.894, 0.918, and 0.735, respectively. In the follow-up test results for 12 patients after 6 months, the average of the AUC values for the five scores was 0.822. This study showed the feasibility of predicting vocal recovery after 3 months using the spectrogram. We expect this model could be used to relieve patients' psychological anxiety and encourage them to actively participate in speech rehabilitation.

[Factors associated with an unfavorable evolution in patients diagnosed with COVID-19 and followed up in primary care in 2020]. / Factores asociados con una evolución desfavorable en pacientes diagnosticados de COVID-19 y seguidos en atención primaria en 2020.

AIM: To know the factors associated with an unfavorable evolution (UE) of patients diagnosed with COVID-19 with total or partial follow-up in primary care. DESIGN: A case series. SETTING: Urban health center. PARTICIPANTS: By systematic sampling, patients ≥18 years, diagnosed with COVID-19, with analytical confirmation, in 2020 and followed up by their family doctors, were selected. MAIN MEASUREMENTS: Dependent variable: hospital admission or death due to COVID-19. INDEPENDENT VARIABLES: age, sex, medical background, clinical data and treatments related to the disease. Statistical analysis, with SPSS 25.0: descriptive analysis, comparison of proportions (chi square) and medians (Mann-Whitney U). The analysis is completed with logistic regression. RESULTS: 610 patients were included in the study. The median age was 49 years (interquartile range: 35-61); 51.8% were women; 14.9% presented UE (95% CI: 12.0-17.8). The sociodemographic variables or the variables related to medical background that showed an independent association with UE were age (OR: 1.066; 95% CI: 1.038-1.095), sex (OR for men: 3.277; 95% CI: 1.304-8.235) and being a smoker or former smoker (OR: 2.565; 95% CI: 1.135-5.800). Regarding the clinical variables of the disease, an association was found for altered consciousness (OR: 62.829; 95% CI: 9.177-430.149), dyspnea (OR: 14.339; 95% CI: 6.046-34.009), expectoration (OR: 4.764; 95% CI: 1.858-12.213)) and asthenia (OR: 3.993; 95% CI: 1.705-9.351). CONCLUSIONS: 14.9% of the patients diagnosed with COVID-19 presented an UE. Older age, male sex and being a smoker or former smoker increased the probability of it. Altered consciousness, dyspnea, expectoration, and asthenia were the clinical data that best predicted UE.

REHABILITATION OF PATIENTS WITH LONG-TERM AFTEREFFECTS OF MILD COMBAT TRAUMATIC BRAIN INJURY.

OBJECTIVE: The aim: To analyze the effect of Korean red ginseng on status of the vegetative nervous system and well-being of patients with asthenic syndrome assotiated with mild combat traumatic brain injury. PATIENTS AND METHODS: Materials and methods: We have examined 42 patients. Duration of their injury was from 4 to 6 years. We have investigated the indices of the vegetative tonus, vegetative reactivity and vegetative provisioning, its neurally mediated component - adrenaline and noradrenaline and melatonin hormone in daily urine. Some neuropsychological data were investigated with the help of HAM method (Health, Activity and Mood scale). RESULTS: Results: After the treatment with Korean red ginseng all indices of the vegetative nervous system improved significantly. Accordingly, the rates of adrenaline and noradrenaline and the hormone melatonin, which were reduced before treatment in most of the examined, increased. The HAM values also improved after the treatment. CONCLUSION: Conclusions: The use of Korean red ginseng restores efficiency, sleep, activity, and improves the mood of patients with aftereffects of mild traumatic brain injury and does not cause any adverse reaction.

GENDER FEATURES OF DEPRESSIVE AND ANXIOUS MANIFESTATIONS OF THE LUNG CANCER PATIENTS.

OBJECTIVE: The aim: To examine the features of depressive and anxiety phenomenology in lung cancer, taking into account the gender factor. PATIENTS AND METHODS: Materials and methods: 112 patients with a primary diagnosis of stage II and III lung cancer were clinically and psychologically examined using HDRS, HARS, BDI, C. Spilberger's Reactive and Personality Anxiety Scale. RESULTS: Results: It was found that the core affective psychopathological symptoms of patients with lung cancer are manifestations of depression (96.3% of men, 96.8% of women (p>0.05), 96.4% together) and anxiety (77.8% , 93.5% (p<0.05) and 82.1%) in combination with asthenic-neurotic (67.9%, 61.3% (p> 0.05) and 66.1%) and affective labile (54.3%, 61.3% (p>0.05) and 56.2%) manifestations; additional symptoms are apathetic (25.9%, 9.7% (p<0.05) and 21.4%), obsessive (19.8%, 38.7% (p<0.05) and 25.0%) and dysphoric (23.5%, 6.5% (p<0.05) and 18.7%) manifestations. The severity of depressive and anxiety of women is higher than of men; the severity of depressive-anxiety manifestations corresponds to a moderate level: depression by HDRS - 11.6±1.7 points, 15.6±6.3 points (p<0.05) and 12.7±4.0 points; BDI depression - 15.7±6.3 points, 23.7±13.9 points (p<0.05) and 17.9±9.7 points; HARS anxiety - 9.3±2.8 points, 11.5±3.7 points (p<0.05) and 9.9±3.2 points, and reactive anxiety - 44.4±11.1 points, 47.9±15.5 points (p<0.05) and 45.4±12.5 points. The identified differences can be explained by different gender models of psychological response. CONCLUSION: Conclusions: The core affective symptoms of patients with lung cancer are manifestations of depression and anxiety in combination with asthenic-neurotic and affective-labile manifestations; additional are apathetic, obsessive and dysphoric manifestations.

[On the specific treatment of asthenic states: focus on sulbutiamine].

In this article, we try to present the available data regarding the pharmacokinetics and pharmacodynamics of sulbutiamine (Enerion), the mechanisms of its anti-asthenic action. Then we analyze and summarize the available evidence base considering the efficacy and safety of Enerion for the treatment of asthenic syndromes. Then we compare Enerion with some other drugs. The results of our review indicate the high efficacy and safety of sulbutiamine in the treatment of asthenia. Our results also show that Enerion has some clinically relevant advantages over all alternatives we reviewed there.

[Prospects and possibilities for the treatment of patients with long COVID-19 syndrome].

AIM: To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19). MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax® enrolled 160 patients 12-16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft-Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index. RESULTS: The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax® drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale. CONCLUSION: Our study clearly demonstrated the efficacy and high safety profile of Brainmax® in a representative sample of patients with the post-COVID syndrome.