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Updated systematic review and network meta-analysis of first-line treatments for metastatic renal cell carcinoma with extended follow-up data
No full textAbstractImmune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.</jats:p
Рецензия на книги: Панова И.В., Панов А.Б. Медицинское право (административно-правовые основы здравоохранения): монография. Москва: Центр публичного права; Саратов: Наука, 2024. 231 с.; Панова И.В., Панов А.Б. Курс лекций по медицинскому праву (административно-правовые основы здравоохранения): учебное наглядное пособие. Москва: Центр публичного права; Саратов: Наука, 2024. 673 с
No full textThe monograph and the course of lectures on Medical Law give a systematic presentation of the administrative and legal foundations of Russian healthcare on the basis of the current legislation concerning the basics of protecting the health of citizens in the Russian Federation. The books represent the first experience in the jurisprudence of Public Law research of medical and industry issues. The monograph and the course of lectures aim at both familiarizing students, postgraduates, lawyers and doctors with Medical Law from the point of view of public administration, administrative law and process and at administrative responsibility, and teaching skills in applying the acquired knowledge in practice, in health care management and organization of activities related to the protection of citizens' health.В монографии и курсе лекций по медицинскому праву дано системное изложение административно-правовых основ российского здравоохранения на базе действующего законодательства об основах охраны здоровья граждан в Российской Федерации. Книги представляют собой один из первых в юриспруденции опытов системного публично-правового исследования медико-отраслевых вопросов. Монография и курс лекций имеют целью как ознакомление студентов, аспирантов, юристов и медиков с медицинским правом с точки зрения публичного управления, административного права и процесса, а также административной ответственности, так и обучение навыкам применения полученных знаний на практике, в управлении здравоохранением и организации деятельности, связанной с охраной здоровья граждан
О РАБОТАХ Я. П. ТЕРЛЕЦКОГО ПО СТАТИСТИЧЕСКОЙ ФИЗИКЕ
No full textIn connection with 110th anniversary of Professor Ya. P. Terletsky the short review of main results of his scientific school in the field of statistical physics and thermodynamics is given. On the grounds of the analysis of Terletsky's scientific publications (including his doctoral thesis and the textbook for universities) his personal contribution to the solution of most actual problems within Gibbs approach is described. Firstly, the achievements in the approximate solution of the ergodic hypothesis are discussed as well as the obtaining of the expression for non-equilibrium entropy. The important result concerning the Brown motion of the classical/quantum oscillator in the thermal bath is also described.В связи с 110-летней годовщиной со дня рождения профессора Я. П. Терлецкого дан краткий обзор основных результатов его научной школы в области статистической физики и термодинамики. На основе анализа научных публикаций Я. П. Терлецкого (в том числе его докторской диссертации и учебника для университетов) описан его личный вклад в решение наиболее актуальных проблем в рамках подхода Гиббса. В первую очередь отмечены достижения в приближённом решении эргодической проблемы, а также в получении выражения для неравновесной энтропии. Отмечен также важный результат по описанию броуновского движения классического/квантового осциллятора в термостате
Anatomical, pathological, and histological features of experimental respiratory infection of birds by biofilm-forming bacteria Staphylococcus aureus
No full textBackground and Aim: The pathogenesis of staphylococcal infections is mediated by virulence factors, such as enzymes, toxins, and biofilms, which increase the resistance of microorganisms to host immune system evasion. Testing and searching for standardized multi-level algorithms for the indication and differentiation of biofilms at the early stages of diagnosis will contribute to the development of preventive measures to control the critical points of technology and manage dangerous risk factors for the spread of infectious diseases. This research aimed to study the main stages of Staphylococcus aureus biofilm formation in in vitro experiments and to analyze the dynamics of respiratory syndrome development in chickens infected with these bacteria. Materials and Methods: Experimental reproduction of the infectious process was performed using laboratory models: 10-day-old White Leghorn chickens (n = 20). Before the experiments, the birds were divided into two groups according to the principle of analogs: Group I (control, n = 10): the birds were intranasally inoculated with 0.5 cm3 of 0.9% NaCl solution; Group II (experiment, n = 10): the birds were intranasally inoculated with a suspension of S. aureus bacteria, 0.5 cm3, concentration 1 billion/cm3. Results: Colonization of individual areas of the substrate under study in vitro occurred gradually from the sedimentation and adhesion of single motile planktonic cells to the attachment stage of microcolony development. Staining preparations with gentian violet due to the “metachromosia†property of this dye are a quick and fairly simple way to differentiate cells and the intercellular matrix of biofilms. Fixation with vapors of glutaraldehyde and osmium tetroxide preserves the natural architecture of biofilms under optical and scanning electron microscopy. Pure cultures of S. aureus microorganisms were isolated from the blood, lungs, small intestine, liver, kidneys, and spleen after 5–10 days during experimental infection of chickens. Clinical signs of respiratory syndrome developed within 5–6 days after infection. Acute and subacute serousfibrinous airsacculitis, characterized by edema and thickening of the membranes of the air sacs and the presence of turbid, watery, foamy contents in the cavity, was the most characteristic pathomorphological sign. The signs of acute congestive hyperemia and one-sided serous-fibrinous pneumonia developed with significant thickening of fibrinous deposits. In Garder’s gland, there was an increase in the number of secretory sections, indicating hypersecretion of the glands. In the lymphoid follicles of Meckel’s diverticulum, leukocytes, usually lymphocytes, and pseudoeosinophils were detected. Conclusion: Hydration and heteromorphism of the internal environment of biofilms determine the localization of differentiated cells in a three-dimensional matrix for protection against adverse factors. The most characteristic pathomorphological sign was the development of acute and subacute serous-fibrinous airsacculitis when reproducing the infectious process in susceptible models. There was a significant thickening of fibrinous deposits and signs of acute congestive hyperemia and one or two serous-fibrinous pneumonia developed. Keywords: airsacculitis, avian, biofilm, pathogenesis, respiratory syndrome pneumonia, Staphylococcus aureus.</jats:p
Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort
No full textCertain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population
Effect of lesion dimension on survival in patients with T1a renal cell carcinoma who underwent deferred surgery
No full textSmall renal masses (SRMs) have been shown to have low malignant potential. Active surveillance (AS), typically characterized by regular follow-up and delayed nephrectomy if necessary, is recommended as an option for frail patients with SRMs. Nevertheless, the impact of tumor size on survival in T1a RCC patients undergoing delayed nephrectomy for SRMs remains unclear. Patients diagnosed with non-metastatic T1a RCC who underwent nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database and divided into immediate ( 0.05), however this may be due to sample size limiting statistical power. Based on the SEER database, we found that with a median delay of 7 months, 2 cm may be an appropriate cut-off point of delayed nephrectomy for patients diagnosed with non-metastatic T1a RCC
