Sechenov Medical Journal

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Vol 10, No 4 (2019)
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4-11 562

Immune checkpoint inhibitors (ICPIs) agents can cause endocrine immune-related adverse events (irAEs).

Aim. Determine the incidence, time of onset and risk factors of endocrine irAEs in cancer patients treated with anti-PD1 and anti-CTLA-4 immunotherapy.

Materials and methods. This is a retrospective single-center study that included 61 patients aged 28 to 81 years with diagnosed cancer of the lungs, ovaries, esophagus, stomach, bladder, kidney, and pleural mesothelioma. 44 (72%) patients received anti-PDL1/anti-PD1 monotherapy and 17 (28%) received a combination of anti-PD1 + anti-CTLA-4. Calculated: odds ratio (OR) and 95% confidence interval (CI).

Results. The incidence of endocrine irAEs was 23% (14 patients): thyroiditis (13%), hypophysitis (8%), adrenal insufficiency and diabetes mellitus (2–3%). IrAEs occurred in 9 (20%) patients with monotherapy and in 5 (35%) patients when using a combination of drugs (p=0.318). The average time of onset of irAEs did not differ depending on the applied regimen and amounted to 6 [4–18] weeks. Symptomatic irAEs developed in 2 (13%) patients. Discontinuation of ICPI therapy due to irAE was not required in any case. Risk factors: age younger than 61 years old – OR 4.4 (95% CI 1.198–16.242), female OR 2.4 (95% CI 0.67–8.591), presence of stage IV disease – OR 2.4 (95% CI 0.689–8.362), combination therapy OR 1.855 (95% CI 0.548–6.277), previous endocrine pathology – OR 0.813 (95% CI 0.152–4.356).

Conclusions. The incidence of endocrine irAEs when using ICPI is 23%. Thyroiditis and hypophysitis develop more often. The odds are higher in patients younger than 61 years. In most cases, irAEs are not symptomatic and do not require discontinuation of ICPI therapy.

12-20 576

In the experimental model of cerebral ischemia, citicoline has shown greater effectiveness with its preventive use compared with therapeutic one.

Aim. To study the main clinical outcomes and the dynamics of morphometric indicators of ischemic brain damage according to computed tomography (CT) data in patients with meningiomas of the skull base in the postoperative period against the background of prophylactic and therapeutic administration of citicoline.

Materials and methods. The study included 53 patients aged 40 to 69 years with the skull base meningiomas. The first (control) group (n=17) and the third group, in which citicoline was administered in the postoperative period for 7–21 days at a dose of 1000 mg 2 times a day intravenously (n=25), were formed retrospectively. The second group (n=11), in which citicoline was administered prophylactically 1.5–2.5 hours before surgery at a dose of 2000 mg intravenously, was formed prospectively. We evaluated the main clinical outcomes and CT morphometry data.

Results. The average time spent in the intensive care unit was minimal in the second group: 9.6±3.2 days vs 17.6±3.7 days in the control (p=0.049). Postoperative mortality was 24% in the control group, 9% in the second group, and 20% in the third group. The survival time in the first group was less than 21 days, over 21 days in the second and third groups. The groups did not differ in neurological outcomes and overall in-hospital stay. The average volume of ischemic brain damage on the first day after surgery in the second group was less than in the control group, and amounted to 111.7±15.2 cm3 against 151.3±17.1 cm3, respectively (p=0.044).

Conclusion. The prophylactic administration of citicoline before a tumor removal operation may have effective potential for reducing the severity and prevalence of ischemic cerebral edema. Further randomized clinical trials are needed.

21-30 533

Induction of oxidative stress is one of the main mechanisms responsible for the development of micro- and macrovascular angiopathy in patients with type 2 diabetes mellitus (DM-2).

Aim. To evaluate the influence of long-term treatment with inhibitors of dipeptidyl peptidase-4 (DPP-4) on the characteristics of oxidative stress and the state of antioxidant defense system in rats with induced DM 2.

Materials and methods. We divided 60 Wistar albino rats into 5 groups: group 1 (control) – normal animals; groups 2–5 rats with DM 2, induced by streptozotocin: group 2 – without treatment with DPP 4; group 3 – rats, treated with saxagliptin (0.45 mg/kg); group 4 – rats, treated with sitagliptin for 3 weeks (0.6 mg/kg); group 5 – rats, treated with vildagliptin (9 mg/kg). At the end of the experimental phase we determined the level of superoxide anion radical (O2-), hydrogen peroxide (H2O2), nitrite (NO2-), reduced glutathione, as well as the activity of catalase and superoxide dismutase (SOD) in the blood of rats using a diode array spectrophotometer.

Results. Induction of DM-2 in experimental animals led to a significant increase of reactive oxygen species (ROS): superoxide radical and hydrogen peroxide and to decrease in NO2-, reduced glutathione, catalase and SOD activity. Comparing groups 3–5 with group 2, treatment with DPP-4 inhibitors reduced excessive generation of superoxide radical (O2-) and hydrogen peroxide (H2O2) (especially significant in the group with vildagliptin) and increased the activity of catalase and superoxide dismutase (especially significant in the group with v sitagliptin) but the normal values, received in group 1, were not reached. Treatment with all DPP-4 inhibitors brought the level of nitrite (NO2-) up to normal, comparable with group 1.

Conclusions. DPP-4 inhibitors suppress systemic oxidative stress in rats with induced DM 2 via reduction of prooxidative molecules production and activation of antioxidant defensive system.


31-39 648
Modern approaches in medicine are based on the principles of evidence-based and balanced decisions in the age of personalized evidence-based medicine. Cochrane collaboration plays an important role in the development of evidence-based medicine; it’s methodology of meta-analysis, summarizing the scientific evidence from randomized clinical trials (RCTs) to answer the clinical questions about safety and effectiveness of various medical interventions. The article provides a brief historical background on the main milestones in the development of the methodology of evidence-based medicine, on the formation of Cochrane collaboration. The authors explain the concept of meta-analysis and systematic review, their types, methodological features and current requirements. The article defines the sequence of writing a metaanalysis: determing a task, inclusion and exclusion criteria, systematic search for randomized clinical trials, methodological assessment of studies, error risk assessment, meta-analysis models: fixed and random effects; determination of heterogeneity, presentation of meta-analysis results, assessment of confidence level using the GRADE system. The domestic experience of establishing evidence-based medicine in Russia and the contribution to the Cochrane international collaboration are represented separately: the opening of the first branch of the North European Cochrane Cooperation Center in Russia in 1998, the development of educational activities, the work of the Russian clone of the Cochrane Hepatobiliary Group and the appearance of the first qualitative meta-analysis, written by Russian authors, the introduction of an adapted system and the development of a national system for supporting medical decisions. The policy of introducing evidence-based medicine at the state level, legal acts, and the prospects for the development of evidence-based medicine in Russia are reflected.


40-48 589

Introduction. Arteriovenous malformations (AVM) of the head represent the rare lesions that have a congenital, traumatic or post-infectious nature. In the last decade, endovascular methods have become the most prevalent in the treatment of AVM. Staged embolization is performed to achieve maximum effect and minimize the complications.

Case report. A 30-year-old female patient is presented with complaints of enlarged vessels in the frontal and parietal regions. CT-angiography scan and cerebral angiography showed extracranial AVM of the fronto-parietal regions with afferent vascular supply from the right and left superficial temporal and ophtalmic arteries with significant expansion of the afferent arteries and the presence of varix dilatation of the draining veins. Two-stage endovascular embolization of AVM was performed. The first stage was embolization of the afferent vessels from the left superficial temporal artery system with exclusion of 60–65% AVM volume. Three months later, the second stage was performed with embolization of the afferent vessels from the right superficial temporal artery system and the exclusion of 75–80% of the residual volume of AVM. The non-adhesive composition SQUIDR12 (Emboflu, Switzerland) and glue composition PHILR25% (Microvention, USA) were used. A good aesthetic effect was achieved. Postoperative complications were not observed. There was no recurrence during the observation within a year.

Summary. The staging and the use of various liquid embolization agents in the treatment of AVM of the head allow to achieve a good aesthetic outcome and prevent complications associated with facial soft tissue necrosis.

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ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)