Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Менингококковая инфекция у детей в период 2012–2021 гг. Основные итоги ретроспективного многоцентрового исследования, проблемы сегодняшнего дня

The heavy burden of meningococcal infection is associated not only with life-threatening complications in the acute period and high mortality in invasive forms of the disease, but also with severe consequences in survivors, who are not recorded in our country.The aim of study: to analyze clinical manifestations, complications of the acute period and outcomes of invasive forms of meningococcal disease in children in various regions of the Russian Federation.Materials and methods: an analysis of data from 1327 inpatient medical records of children with an invasive meningococcal infection from 14 regional centers of the Russian Federation for 2012-2021 was carried out (28.3% of cases of the disease in children in the represented federal districts).Results: it was found that young children predominated among the patients – the median was 27.4 (10.7-70.4) months. Complications of the acute period, often combined, were observed in 47.6% of cases. The development of septic shock was noted in 30.4%, Waterhouse-Friderichsen syndrome in 6.6%, carditis in 2.9%, cerebral edema in 15.7%, arthritis in 1.4% of cases; the formation of hydrocephalus, subdural effusion, sensorineural hearing loss in 1.8%, 0.6%, 1% of children, respectively. The presence of soft tissue necrosis requiring surgical intervention was noted in 3.5% of cases. Mortality rate was 10.1%. At the time of discharge from the hospital, 30% of children had complications associated with meningococcal infection: organ dysfunction/ failure in 13.2% of patients (severe in 1.3%), cerebral insufficiency in 19.6%; severe psycho-neurological deficits, sensorineural hearing loss, problems associated with the need for orthopedic/surgical interventions accounted for 0.7%, 0.6% and 0.8%, respectively.Conclusion. Considering the epidemiological features of meningococcal infection – the risk of a sharp increase in morbidity in short periods of time, the life-threatening nature of the disease itself, it is necessary to remain alert to these risks and take all possible measures to prevent the disease using all available means, the most effective of which is vaccine prevention.Тяжелое бремя менингококковой инфекции связано не только с жизнеугрожающими осложнениями острого периода и высокой летальностью при генерализованных формах заболевания, но и с тяжелыми последствиями у выживших, учет которых в нашей стране не ведется.Цель: проведение анализа клинических проявлений, осложнений острого периода и исходов генерализованных форм менингококковой инфекции у детей в различных регионах Российской Федерации.Материалы и методы: проведен анализ данных 1327 медицинских карт (форма 003/у) детей с генерализованной формой менингококковой инфекции из 14 региональных центров Российской Федерации за 2012– 2021 гг. (28,3% случаев заболевания у детей в представляемых федеральных округах).Результаты: установлено, что среди больных преобладали дети раннего возраста – медиана составила 27,4 (10,7–70,4) месяцев. Осложнения, часто сочетанные, в остром периоде заболевания наблюдались в 47,6% случаев: септический шок в 30,4%, синдром Уотерхауза – Фридериксена в 6,6%, кардит в 2,9%, отек головного мозга в 15,7%, артриты в 1,4%, гидроцефалия в 1,8%, сенсоневральная тугоухость в 1%, субдуральный выпот в 0,6% случаев. Наличие некрозов мягких тканей, требовавших хирургического вмешательства, отмечено в 3,5% случаев. Летальность составила 10,1%. На момент выписки из стационара у 30% детей выявлялись осложнения, в том числе выраженная органная дисфункция в 1,3%, грубый психоневрологический дефицит, сенсоневральная тугоухость; осложнения, требующие проведения ортопедических/хирургических вмешательств, составили 0,7%, 0,6% и 0,8% соответственно.Анализ полученных данных позволил вскрыть существующие проблемы, касающиеся клинической и этиологической диагностики заболевания, возможностей выявления осложнений острого периода и учета последствий генерализованных форм менингококковой инфекции.Заключение. Учитывая эпидемиологические особенности менингококковой инфекции (риск резкого подъема заболеваемости в короткие временные промежутки, жизнеугрожающий характер самого заболевания), необходимо сохранять настороженность в отношении данных рисков и предпринимать все возможные меры для профилактики заболевания с использованием всех доступных средств, наиболее эффективным из которых является вакцинопрофилактика

CHARACTERISTICS OF CLINICAL PICTURE AND BIOLOGIC FEATURES OF RARE BREAST CANCER FORMS

Low incidence and difficulties of histological type identification of rare breast cancer forms preoperatively renders paramount importance to the detailed study of all cases revealed. Within the bounds of the research which is under the way in our center, we carried out an analy- sis of patients’ records treated in the N.N. Blokhin Russian Cancer Research Center from 1985 to 2005. Overall, 1053 cases of rare breast cancer forms were diagnosed including 364 patients with tubular, 231 — mucous, 190 — medullar, 126 — papillary and 142 — metaplas- tic carcinomas. The article discusses the issues of clinical course, presentation, treatment and prognosis of rare forms of breast cancer

TREATMENT OF THE T3—4N0M0 BREAST CANCER

The aim of the study was to determine the most effective regimens of the neo- and adjuvant therapy of the primary breast cancer of the T3—4N0M0 stages. The data of the clinical observations of the 145 patients with the locally advanced T3—4N0M0 breast cancer, who underwent treatment in the N.N.Blokhin CRC over the period of 1998—2003, were used in the study. The mean age of the patients was 55,3±12,9 years (from 19 to 83 years, median-55 years). The duration of the observation of the patients was 46,5±28,51 months (from 3,6 to 109,4 months, median-44,5 months). For patients with the breast cancer of the T3—4N0M0 stages combined treatment modality was implemented with the use of neo- and adjuvant therapy in all the cases

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry)