Aim. To assess the efficacy and safety of lenvatinib plus pembrolizumab for the treatment of mismatch repair-proficient (pMMR) endometrial cancer (EC) in routine clinical practice in Russia.Materials and methods. This multicenter, retrospective, cohort study included 114 patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between December 2020 and November 2024. Patients with histologically verified EC without microsatellite instability were included. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed; the objective response rate and the toxicity profile of therapy were assessed.Results. Median patients’ age was 66.5 (33–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (72.8 %); serous adenocarcinoma was diagnosed in 18.4 % of cases, other subtypes – in 8.8 %. The median progression-free survival was 8.15 months (95 % confidence interval 0.4–41.1). Objective response rate was 38.0 %. The median overall survival was not achieved with a median follow-up of 12.23 months. During treatment, dose reduction rate due to adverse events was 50 %. The most frequent adverse events were hypertension (n = 64; 56.1 %), fatigue (n = 45; 39.5 %), and diarrhea (n = 20; 17.5 %).Conclusion. In the conducted study of routine clinical practice in Russian patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR/MSS), lenvatinib plus pembrolizumab showed good efficacy with a manageable safety profile.
The review considers the current knowledge about the structure of the thyroid-stimulating hormone (TSH) receptor, itsfunctions in various organs and tissues, the mechanisms of stimulating action of TSH on the synthesis of thyroid hormones,and the influence of TSH signaling on cell proliferation and differentiation in the context of evolutionary genetics and thehierarchical target organ regulation of pituitary hormones. Thyroid-stimulating hormone and its associated receptor (TSHR)are crucial for proliferation of thyrocytes and realization of their functional activity. In addition, according to modern ideas,the TSH/TSHR complex is considered an important modulator of oncogenesis and tumor progression. The interaction ofthe G-protein-coupled receptor (GPCR) and the ligand initiates a number of signaling cascades directly involved in cellproliferation and survival not only in normal tissues, but also in pathologically altered extra-thyroid organs and the thyroidgland. The relationship of hypo- and hyperthyroid states with the risk of promotion of tumors of various localization, thetypes of thyroid hormone influence on cellular metabolism are also considered. In addition to the most studied role –regulation of basal metabolism, the most important function of T3 and T4 is to control cell migration and differentiation viaboth genomic and non-genomic effects, which plays a key role in the process of ontogenesis and should be investigatedas a tumor growth mechanism. Most studies, both in vivo and in humans, observe the association of hypothyroidism withdecreased cancer incidence and tumor growth rate. Some publications demonstrate a smaller proportion of lymph nodeinvolvement, a higher rate of localized forms, lower mortality in cancer patients with hypothyroidism, while other studiesshow a correlation between hyperthyroidism and increased cancer risk, larger primary tumors, regional metastasis,and decreased survival of cancer patients. However, the study design features, lack of data on the age, gender, tumormolecular subtype, ethnicity, region of residence, iodine availability, grade of thyroid function suppression after theanticancer treatment are extremely important for each clinical case due to the ambiguity of the thyroid hormone effect ontumor progression in various cancers. It is important to note that although direct monitoring of thyroid function, includingfree T4 and TTH, is necessary, it is not sufficient to assess the thyroid status of a patient. The profile of plasma bindingproteins, tissue metabolism, receptor profile, the direct effect of thyrotropin releasing factor and TSH on tissues, thepresence, concentration, and type of the thyroid stimulating hormone receptor autoantibodies are important, and furtherscientific research is required in this direction. In this review, 106 publications from the Scopus, PubMed, Web of Sciencebiomedical literature databases were analyzed, and 72 publications were included В контексте эволюционной генетики и иерархической оси регуляции органов-мишеней гипофизарных гор-монов в обзоре рассмотрены современные представления о строении рецептора тиреотропного гормона(ТТГ), его функциях в различных органах и тканях, механизмах стимулирующего действия ТТГ на синтезтиреоидных гормонов, влиянии ТТГ-сигналинга на процессы пролиферации и дифференцировки клеток.ТТГ и связанный с ним рецептор (ТТГР) имеют решающее значение для пролиферации тироцитов и осу-ществления их функциональной активности. Кроме того, по современным представлениям, комплекс ТТГ/TТГР считается важным модулятором онкогенеза и прогрессирования опухолей. Взаимодействие рецепто-ра, связанного с G-белком (GPCR), и лиганда запускает целый ряд сигнальных каскадов, непосредственноучаствующих в пролиферации и выживании клеток не только в нормальных тканях, но и в патологическиизмененных экстра-тиреоидных органах и щитовидной железе (ЩЖ). Также рассмотрена связь гипо- и ги-пертиреодных состояний с риском инициации и промоции опухолей различной локализации, типы влияниягормонов ЩЖ на клеточный метаболизм. Помимо наиболее изученной роли – регуляции основного обмена,важнейшей функцией Т3 и Т4 является управление миграцией и дифференцировкой клеток посредствомреализации как геномных, так и негеномных эффектов, что играет ключевую роль в процессе онтогенеза,а также должно учитываться при изучении механизмов опухолевого роста. Для большинства исследова-ний как in vivo, так и в человеческой популяции прослеживается взаимосвязь гипотиреоза со снижениемчастоты развития ряда онкологических заболеваний и скорости роста опухолей. Некоторые публикациисвидетельствуют о меньшем вовлечении лимфатических узлов, большей частоте локализованных форм,более низкой смертности у онкологических пациентов с гипотиреозом, в то время как в других работахпродемонстрирована положительная корреляция гипертиреоза и риска развития, размера первичнойопухоли, регионарного метастазирования рака, низкой выживаемости онкологических больных. Однакоособенности дизайна исследований, нередкий недоучет возраста, пола, молекулярного подтипа опухоли,этнической принадлежности пациентов, региона проживания, йодной обеспеченности, степени угнетенияфункции ЩЖ на фоне проводимого противоопухолевого лечения являются крайне важными для анализафакторами в каждом отдельном клиническом случае ввиду неоднозначности влияния тиреоидных гормо-нов на скорость опухолевой прогрессии при различных типах неоплазий. Важно отметить, что при всейнеобходимости непосредственного мониторинга функции ЩЖ, включающего определение свободного Т4и ТТГ, судить о тиреоидном статусе пациента на этом основании можно не в полной мере. Имеет значениепрофиль плазменных связывающих белков, тканевый метаболизм, рецепторный профиль, прямое влияниетиролиберина и ТТГ на ткани, наличие, концентрация и вариант действия антител к рецепторам гормоновтиреоидной оси, что делает актуальными дальнейшие научные изыскания в этом направлении. При подготовке обзора был проведен анализ 106 публикаций из информационных баз биомедицинской литературыScopus, PubMed, Web of Science, в обзор включено 72 публикации.
BACKGROUND: Pectus excavatum is a malformation characterized by deformities of the cartilaginous parts of the ribs and sternum of varying severity and accounts for 75%–91% of all chest wall deformities. Surgical treatment of pectus excavatum in children remains an urgent issue, despite the considerable number of existing surgical correction techniques. These techniques are not universally applicable, especially for asymmetric and rigid forms, requiring ongoing modification and improvement. CASE DESCRIPTION: A 17-year-old patient underwent surgical correction of a severe pectus excavatum complicated by a history of cardiac surgery, namely, median sternotomy and mitral valve prosthesis placement. The surgical procedure involved the release of major vital anatomical structures, the use of an external fixation device providing high corrective force during surgery, and gradual intraoperative correction under cardiac function monitoring. DISCUSSION: Correction of severe pectus excavatum following prior median sternotomy is associated with a high risk of complications, including fatal events such as asystole or massive hemorrhage. In such cases, a minimally invasive thoracoplasty with an additional subxiphoid approach and sternal elevation using an external fixation device is recommended. Conventional sternal elevation techniques (e.g., bone hooks, sutures, and clamps) have been found to be not advisable for pronounced rigid deformities owing to the risk of sternal injury. Moreover, isolated thoracoscopy using the standard MIRPE technique does not ensure the integrity of intrathoracic structures, and traditional bar-flipping maneuver for immediate and forced correction of pectus excavatum is inappropriate. CONCLUSION: Patients with pectus excavatum exceeding the threshold for severe deformity, particularly those with previous cardiac surgery, require a treatment different from standard thoracoplasty. The presented approach, involving the release of major vital anatomical structures and gradual intraoperative correction under cardiac monitoring with an external fixation device, is recommended for managing such complex clinical cases.
INTRODUCTION: Analysis of the effectiveness of treatment for the disease is necessary to improve the medical care provided to the given category of patients. AIM: To determine the effectiveness of pathogenetic therapy of patients with Parkinson’s disease (PD) in the population of the Kursk region depending on age and stage according to the Hoehn–Yahr Rating Scale, and to assess the severity of the disease depending on gender and place of residence. MATERIALS AND METHODS: A total of 100 outpatients with a mixed form of PD aged 45–74 years (of them are 60 women and are 40 men) were examined. The mean age of the patients was 62.7 ± 6.2 years. Most patients lived in the rural region — 61.0% (32 women and 29 men), while 39.0% (28 women and 11 men) lived in the urban area. The severity of the disease was assessed according to the Hoehn–Yahr scale. Cognitive function was studied using the MMSE scale (Mini-Mental State Examination), the Frontal Assessment Battery (FAB), and the Clock Drawing test. RESULTS: The age of PD onset varied from 42 to 70 years (mean age 58.5 ± 6.7 years); in rural residents — 58.8 ± 6.9 years (in men — 58.6 ± 5.6 years, in women — 58.9 ± 5.8 years); in urban residents — 58.2 ± 6.5 years (in men — 57.1 ± 5.4 years, in women — 58.6 ± 6.9 years); p 0.05. Monotherapy with L-DOPA drugs was effective in 50.0% of cases, and with dopamine receptor agonists (DRA) in 53.0% of cases, combination therapy with DRA and L-DOPA preparations appeared to be more effective and made 72.5% of cases. CONCLUSION: In the studied cohort of patients with Parkinson’s disease, patients living in rural areas outnumbered the urban patients 1.5 times, however, the mean age of onset was comparable. Therapy for patients with Parkinson’s disease was staged consisting in prescribing monotherapy at the early stages of the disease with subsequent replacement with a combination of dopamine receptor agonists and levodopa. The greatest treatment efficiency in patients with a mixed form of Parkinson's disease is observed with combination therapy.
Background. Onychocryptosis is damage to the surrounding tissue caused by the nail. The etiopathogenesis of the disease remains poorly understood. Both external factors (poor nail hygiene, tight shoes, mechanical nail trauma) and internal factors (congenital anomalies of the nail plate and bone structures of the phalanges) are believed to play a role in its development. The epidemiological data of the disease are also not fully understood. It is known that onychocryptosis most often develops on the big toes. The clinical presentation of onychocryptosis depends on the severity of the disease, but the main complaint of patients at all stages of the disease is pain, which most often prompts them to seek medical attention. Swelling of the affected lateral nail fold is also characteristic of the clinical picture of onychocryptosis, as well as the presence of discharge and/or oozing in later stages of the disease. Diagnosis of onychocryptosis is usually straightforward and is based on the patient's medical history and clinical presentation. In most cases, diagnosis is made without the use of additional diagnostic methods. Currently, there are numerous approaches to correcting onychocryptosis, including both conservative and surgical methods. Among the conservative treatments for onychocryptosis, orthonyxia stands out. This method can be effective in treating the disease, ensuring minimal impact on the patient's quality of life and not requiring a lengthy rehabilitation period after treatment. Other practical advantages of orthonyxia include its virtually complete painlessness and the ability to adjust it during treatment. Orthonyxia is a relatively new method. Despite this, it is gradually finding its place in surgical, orthopedic, and dermatological practice, as evidenced both in clinical medicine and in scientific publications. Results. This article presents clinical cases of successful orthonyxia in correcting mild to moderate onychocryptosis. It also highlights the potential role of orthonyxia as the most optimal treatment option for onychocryptosis in the early stages.
