ОЦЕНКА ЭФФЕКТИВНОСТИ И ТОКСИЧНОСТИ ИНТЕНСИФИЦИРОВАННОГО ПЛАТИНОСОДЕРЖАЩЕГО РЕЖИМА ПРЕДОПЕРАЦИОННОЙ ХИМИОТЕРАПИИ ПРИ ПЕРВИЧНО ОПЕРАБЕЛЬНОМ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ С ТРОЙНЫМ НЕГАТИВНЫМ ФЕНОТИПОМ

Triple-negative breast cancer (TNBC) is characterized by an aggressive behavior, highly sensitivity to chemotherapy, early recurrence, and also the absence of known targets for targeted therapies. TNBC is extremely impotant search for intensive regimens of neoadjuvant chemotherapy, because of insufficient effectiveness of conventional therapies. The aim of the study was to evaluate the efficacy and toxicity of cisplatin, doxorubicin, paclitaxel in patients with early breast cancer with triple-negative phenotype in preoperative mode. The study included 41 patients with early breast cancer, triple negative phenotype (T1–2 N0–1M0). Patients were treated with cisplatin 30 mg/m2 / IV., Doxorubicin 25 mg/m2 / IV., Paclitaxel  100 mg/m2 / IV. weekly for planned 8 weeks  with G-CSF 300 mcg 2–4 days followed by surgery. The rate of objective response was 38/40 (95%) complete response – 12/40 (30%), partial regression – 26/40 (65%), stabilization – 2/40 (50%). 40 hftients were treated with surgery, 26/40 (65%) achieved a complete pathological regression. 2-year disease-free survival – 89.4%. 2-year overall survival – 95.1%. Combination of cisplatin, doxorubicin, paclitaxel, it proved its high efficacy in patients with early breast cancer with triple-negative phenotype, despite it’ high toxicity. Тройной негативный рак молочной железы (РМЖ) характеризуется агрессивностью течения, высокой чувствительностью к химиотерапии, ранним рецидивированием, а также отсутствием известных мишеней для таргетной терапии. Ввиду недостаточной эффективности стандартных подходов в лекарственном лечении РМЖ с тройным негативным фенотипом представляется чрезвычайно актуальным поиск интенсивных режимов неоадъювантной химиотерапии. Целью исследования являлась оценка эффективности и токсичности комбинации цисплатина, доксорубицина, паклитаксела у больных ранним РМЖ с тройным негативным фенотипом в предоперационном режиме. В исследование включены 41 больных ранним РМЖ с тройным негативным фенотипом (T1–2 N0–1M0). Больные получали лечение по схеме: цисплатин 30 мг/м2 в/в кап., доксорубицин 25 мг/м2 в/в кап., паклитаксел 100 мг/м2 в/в кап. Еженедельно 8 введений с поддержкой ГКСФ в дозе 5 мкг/кг со 2 по 4 день. Частота развития объективных эффектов во всей группе составила 38/40 (95,0%): полных регрессий – 12/40 (30,0%), частичных регрессий – 26/40 (65,0%), стабилизаций – 2/40 (5,0%). Из 40 прооперированных больных у 26/40 (65,0%) достигнута полная патоморфологическая регрессия. 2-летняя безрецидивная выживаемость – 89,4%. 2-летняя общая выживаемость – 95,1%. Несмотря на относительно высокую токсичность комбинации цисплатина, доксорубицина, паклитаксела, доказана ее высокая эффективность у больных ранним РМЖ с тройным негативным фенотипом

ЭФФЕКТИВНОСТЬ И ТОКСИЧНОСТЬ АЛЬТЕРНИРУЮЩЕГО МНОГОКОМПОНЕНТНОГО РЕЖИМА НЕОАДЪЮВАНТНОЙ ХИМИОТЕРАПИИ МЕСТНОРАСПРОСТРАНЕННОГО РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ С ТРОЙНЫМ НЕГАТИВНЫМ ФЕНОТИПОМ

One way to improve the results of treatment of patients with locally advanced triple-negative breast cancer (TNBC) is to find the most effective neoadjuvant chemotherapy regimen. It has been shown that patients (pts) with TNBC with pathological complete regression (pCR) after neoadjuvant chemotherapy have better survival. The aim of the study was to evaluate the efficacy and toxicity of induction chemotherapy regimen, including 2 consequent chemotherapy regimens: рaclitaxel 60 mg/m2  IV weekly plus сarboplatinum AUC2 IV weekly for 9 weeks, then doxorubicin 25 mg/m2 IV weekly plus cyclophosphamide 50 mg per os q. i. d. plus capecitabine 500 mg t. i. d for 9 weeks. The study included 45 patients with TNBC, stages IIIA, IIIB, IIIC. Overall response rate was 40/45 (88,9%) with 7/45 (15,6%) of complete responses and 33/45 (73,3%) of partial responses. Forty-four patients underwent surgery. Twenty seven patients (61,4%) achieved pCR. Three-year disease-free survival was 71% and overall survival was 81%. The most common types of toxicity were neutropenia (40% grade 3–4), mucositis (55% grade 1–3) and hand-foot syndrome (65% grade 1–3). Despite relatively high toxicity this alternating multicomponent induction chemotherapy regimen had high efficacy. More than half of patients (61.4%) achieved pCR.Одним из путей улучшения результатов лечения больных местнораспространенным раком молочной железы с тройным негативным фенотипом (ТНРМЖ) является поиск максимально эффективных режимов неоадъювантной химиотерапии (ХТ), так как известно, что при достижении полной патоморфологической регрессии (пПР) прогноз заболевания существенно улучшается, приближаясь к прогнозу наиболее благоприятных подтипов. Целью исследования была оценка эффективности и токсичности неоадъювантного режима «карбоплатин AUC2 в/в капельно, паклитаксел 60 мг/м2 в/в капельно еженедельно 9 введений, далее доксорубицин 25 мг/м2 в/в капельно еженедельно 9 введений, циклофосфан 50 мг внутрь ежедневно и капецитабин 1500 мг внутрь ежедневно 9 недель» у больных местнораспространенным ТНРМЖ. В исследование были включены 45 больных с IIIA, IIIB, IIIC стадиями ТНРМЖ. Частота объективных эффектов во всей группе составила 40/45 (88,9%), из них полных регрессий – 7/45 (15,6%), частичных регрессий – 33/45 (73,3%). Из 45 больных, включенных в исследование, 44 были оперированы. У 27 из 44 (61,4%) оперированных больных достигнута пПР. 3-летняя безрецидивная выживаемость составила 71%, а 3-летняя общая выживаемость – 81%. Основными видами токсичности были нейтропения 3–4 ст. (40%), стоматит 1–3 ст. (55%), ладонно-подошвенный синдром 1–3 ст. (65%). Несмотря на относительно высокую токсичность лечения, изученный альтернирующий многокомпонентный режим обладал высокой эффективностью и позволил более чем у половины больных (61,4%) достичь пПР

Cholera: Trends in the Development of the Epidemic Process in 2021, Forecast for 2022

The aim of the work was to summarize the results of cholera monitoring in 2021, to assess current trends in the development of the epidemic process, and to predict the epidemiological situation in the Russian Federation for 2022. It was established that within the period of 2012–2021, 4117264 cases of cholera with the spread of infection across 83 countries on all continents were registered in the world and there was a downward trend in the incidence in Asia and Africa. The dynamics of monthly morbidity in 2021 was associated with emergencies as factors of epidemiological risk. Epidemics and outbreaks of cholera were documented against the background of COVID-19 pandemic and laid a double burden on healthcare systems. At the same time, based on the overview of the results of cholera monitoring in the constituent entities of the Russian Federation, it was shown that the forecast of epidemic well-being given for 2021 was fully justified. It has been determined that the increase in the number of non-toxigenic strains of Vibrio cholerae O1 (67) isolated from water bodies compared to 2020 (25) is mainly due to the appurtenance of a number of isolates to clonal complexes. The study of phylogenetic relation has demonstrated that the detection of strains with genotypes which were previously identified in the isolates evidences the persistence potential. The identification of strains with new genotypes, which were earlier established in the strains circulating in other territories, pointed at the possibility of the occasional importations. The forecast of the epidemiological situation on cholera in Russia for 2022 is associated with the continuous existence of risks of introduction. If these epidemiological risks are not realized, a favorable epidemiological situation is predicted regarding this infection in the country. It is expected that the detection of epidemiologically insignificant strains of V. cholerae O1 in environmental water bodies, along with their clones and/or clonal complexes, will remain, including strains that may be an etiological factor in sporadic cases or outbreaks of disease

Прогностическое значение биологических характеристик резидуальной опухоли после проведения неоадъювантной химиотерапии при раннем раке молочной железы с тройным негативным фенотипом

Neoadjuvant chemotherapy is a widely used approach in patients with early triple-negative and Her2-positive breast cancer (BC). This allows in vivo evaluation of treatment efficacy and reduction of the local treatment extent in some patients, as well as prognosis assessment and the prescription of adjuvant chemotherapy in patients with residual tumors. The study evaluated the predictive value of estimating tumor response to treatment using the RCB (Residual Cancer Burden) staging system and assessed Ki-67 levels and tumor-infiltrating lymphocyte (TIL) concentrations in residual tumors in patients with primary operable BC with triple-negative phenotype (TN BC) receiving neoadjuvant platinum-based chemotherapy. The study revealed that complex assessment of the RCB, Ki-67, and TILs parameters provides more accurate predictive information compared to simply asserting the presence or absence of a residual tumor, and allows assignment of patients to escalation or de-escalation of adjuvant systemic therapy.Неоадъювантная (НА) лекарственная терапия широко применяется в лечении больных тройным негативным и Нег2-позитивным раком молочной железы (РМЖ) ранних стадий. Это позволяет оценить эффективность лечения in vivo, у части больных уменьшить объем локального лечения, а также оценить прогноз и при наличии резидуальной опухоли назначить адъювантную лекарственную терапию. В исследовании изучалась прогностическая значимость оценки ответа опухоли на лечение по системе RCB (Residual Cancer Burden), а также оценены уровень Ki-67 и содержание инфильтрирующих опухоль лимфоцитов (ИОЛ) в резидуальной опухоли у больных первично операбельным РМЖ с тройным негативным фенотипом (ТН РМЖ), получавших НА платиносодержащую химиотерапию (ХТ). Показано, что комплексная оценка показателей RCB, Ki-67 и ИОЛ позволяет получить более точную прогностическую информацию, чем простая констатация наличия или отсутствия резидуальной опухоли, и выделить группы больных для эскалации и де-эскалации адъювантной системной терапии

Influence of the Water Content on the Diffusion Coefficients of Li⁺ and Water across Naphthalenic Based Copolyimide Cation-Exchange Membranes

The transport of lithium ions in cation-exchange membranes based on sulfonated copolyimide membranes is reported. Diffusion coefficients of lithium are estimated as a function of the water content in membranes by using pulsed field gradient (PFG) NMR and electrical conductivity techniques. It is found that the lithium transport slightly decreases with the diminution of water for membranes with water content lying in the range 14 < λ < 26.5, where λ is the number of molecules of water per fixed sulfonate group. For λ < 14, the value of the diffusion coefficient of lithium experiences a sharp decay with the reduction of water in the membranes. The dependence of the diffusion of lithium on the humidity of the membranes calculated from conductivity data using Nernst–Planck type equations follows a trend similar to that observed by NMR. The possible explanation of the fact that the Haven ratio is higher than the unit is discussed. The diffusion of water estimated by 1H PFG-NMR in membranes neutralized with lithium decreases as λ decreases, but the drop is sharper in the region where the decrease of the diffusion of protons of water also undergoes considerable reduction. The diffusion of lithium ions computed by full molecular dynamics is similar to that estimated by NMR. However, for membranes with medium and low concentration of water, steady state conditions are not reached in the computations and the diffusion coefficients obtained by MD simulation techniques are overestimated. The curves depicting the variation of the diffusion coefficient of water estimated by NMR and full dynamics follow parallel trends, though the values of the diffusion coefficient in the latter case are somewhat higher. The WAXS diffractograms of fully hydrated membranes exhibit the ionomer peak at q = 2.8 nm⁻1, the peak being shifted to higher q as the water content of the membranes decreases. The diffractograms present additional peaks at higher q, common to wet and dry membranes, but the peaks are better resolved in the wet membranes. The ionomer peak is not detected in the diffractograms of dry membranes.The authors acknowledge financial support provided by the DGICYT (Dirección General de Investigación Cientifíca y Tecnológica) through Grant MAT2011-29174-C02-02

Features of Etiology of Community-Acquired Pneumonia Associated with COVID-19

Objective: comparative study of the etiological structure of community-acquired pneumonia in SARSCoV-2 “+”and SARS-CoV-2 “-“ patients who sought help from medical organizations in the Rostov Region.Materials and methods. Biological material from 508 patients diagnosed with community-acquired pneumonia who were on outpatient treatment or in hospitals in Rostov-on-Don was studied. Verification of respiratory viruses, including SARS-CoV-2 RNA, as well as M. pneumoniae, C. pneumoniae, and L. pneumophila was performed by polymerase chain reaction in nasopharyngeal smears. Bacteriological analysis of sputum was carried out using differential diagnostic media, identification of isolated pathogens was carried out using time-of-flight mass spectrometry on Autoflex (Bruker Daltonics) with BioTyper 3.0 software.Results and discussion. During the spread of a new coronavirus infection in the Rostov Region, the main etiological agent of community-acquired pneumonia is the new SARS-CoV-2 coronavirus. Specific character of pneumonia in patients with laboratory-confirmed COVID-19 is a higher incidence of mixed infection of both viral and bacterial etiology. Against the background of detection of a new coronavirus infection in patients with pneumonia, cases of detection of other types of coronaviruses have been registered (HKU-1,OC43, HL-63 and 229Е). The most common etiological agent of bacterial pneumonia in patients was Streptococcus spp., both in patients with COVID-19-associated pneumonia and in patients who tested negative for SARS-CoV-2. Coronavirus patients represent a high risk group for the development of mycotic lung lesions