Capivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 study.

BACKGROUND: Capivasertib is a potent, selective pan-AKT inhibitor. In CAPItello-291, the addition of capivasertib to fulvestrant resulted in a statistically significant (P < 0.001) improvement in progression-free survival over fulvestrant monotherapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer and disease progression on or after aromatase inhibitor-based therapy. Characterization of the capivasertib-fulvestrant adverse event (AE) profile as managed in CAPItello-291 can inform future management guidance and optimize clinical benefit. PATIENTS AND METHODS: Seven hundred and eight patients were randomized 1 : 1 to capivasertib (400 mg twice daily; 4 days on, 3 days off) or placebo, plus fulvestrant, on a 4-week cycle. Dose reductions/interruptions for capivasertib/placebo were permitted (up to two dose reductions). Safety analyses included exposure, AE, and clinical laboratory data and were conducted in patients who received at least one dose of capivasertib, fulvestrant, or placebo. Frequent AEs associated with phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) pathway inhibition (diarrhea, rash, hyperglycemia) were characterized using group terms. AEs were summarized using descriptive statistics; time-to-event analyses were conducted. RESULTS: Safety analyses included 705 patients: capivasertib-fulvestrant (n = 355) and placebo-fulvestrant (n = 350). Frequent any-grade AEs with capivasertib-fulvestrant were diarrhea (72.4%), rash (38.0%), and nausea (34.6%); frequent grade ≥3 AEs were rash (12.1%), diarrhea (9.3%), and hyperglycemia (2.3%). Diarrhea, rash, and hyperglycemia occurred shortly after starting capivasertib-fulvestrant [median days to onset (interquartile range) of any grade: 8 (2-22), 12 (10-15), and 15 (1-51), respectively], and were managed with supportive medications, dose reductions, interruptions, and/or discontinuation. Discontinuation rates were 2.0%, 4.5%, and 0.3%, respectively. Overall, 13.0% discontinued capivasertib due to AEs. CONCLUSIONS: Frequent AEs associated with PI3K/AKT pathway inhibition occurred early and were manageable. The low rate of treatment discontinuations suggests that, when appropriately managed, these AEs do not pose a challenge to clinical benefit.

[Particularities of arterial stiffness dynamics on the background of breast cancer chemotherapy].

BACKGROUND: Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. AIM: To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. MATERIALS AND METHODS: 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 2-3 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. RESULTS: The average age of the patients was 45.5±5.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.6±9.3 to 73.3±10.1 beats/min.), a decrease in SBP (from 122.6±9.9 to 116.5±12.3 mmHg) and DBP (from 78.9±8.5 to 76.2±8.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.32±1.41 to 7.85±1.57 m/s), CAVI index on the left (from 6.78±0.81 to 6.5±0.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.7±0.6 to 6.5±0.7 m/s; from 7.0±0.6 to 6.3±0.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. CONCLUSION: A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

[The use of digital radiography in the morphological evaluation of tumor response to neoadjuvant treatment of breast cancer]. / Primenenie tsifrovoi rentgenografii pri morfologicheskoi otsenke otveta opukholi na neoad"yuvantnoe lechenie raka molochnoi zhelezy.

OBJECTIVE: To optimize the morphological assessment of tumor response to neoadjuvant therapy in breast cancer. MATERIAL AND METHODS: A retro- and prospective cohort study was conducted. The object of the study was the surgical material. Macroscopic parameters of residual tumor without and with the use of digital radiography (digital X-Ray) are described and analyzed. PathVision Faxitron imaging system was used for digital X-ray samples. An analysis of dynamics of clinical characteristics was carried out. Two methods of tumor bed examination were compared. RESULTS AND DISCUSSION: The study cohort included 32 women, mean age 45.5±14 years. The correlation of the results of instrumental methods was 0.66 ([95% CI: 0.28; 1], p=0.0002). Microcalcinates were detected by digital X-Ray in 29 (90.6%) cases. Tumor bed sizes determined macroscopically (mean maximal size 6.1 (3.3) cm, median 5.2 (3.4-8.0) cm) and by using digital X-ray (mean maximal size 4.8 (2.6) cm, median 4.1 (2.7-6.2) cm), had statistically significant differences (p<0.0001). The agreement between the two methods of studying the tumor bed was 96.9%. The Cohen's kappa value was 0.95 (p<0.0001). CONCLUSION: Morphological study is an integral part of clinical trials of drug efficacy. With the help of digital X-Ray, the identification of metal markers placed in the tumor bed and microcalcinates is facilitated by the morphologist, and the visibility of the boundaries of the tumor bed is also improved. The results obtained showed that the use of digital X-Ray can improve the accuracy of assessing the degree of morphological regression of breast cancer in response to treatment.

[Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs].

BACKGROUND: Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy. AIM: To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs. MATERIALS AND METHODS: The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1 (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters. RESULTS: A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1 and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1 in urine during the first two weeks of therapy. CONCLUSION: The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1 in urine during the first two weeks after the start of therapy.

[Clinical and laboratory signs and risk factors for nephrotoxicity, associated with antiangiogenic drugs].

BACKGROUND: Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy. AIM: To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs. MATERIALS AND METHODS: The study included 50 patients who received antiangiogenic drugs in different regimens of chemotherapy. Demographic factors, body mass index, blood pressure levels, type of antiangiogenic drug, and concomitant therapy were assessed. Before treatment and over a period of 8 weeks, the levels of hemoglobin, number of platelets and schistocytes, D-dimer levels, serum lactate dehydrogenase (LDH) levels, as well as daily proteinuria and serum creatinine and eGFRCKD-EPI were assessed. Linear regression analysis was performed to assess risk factors for nephrotoxicity and arterial hypertension (AH). RESULTS: The median age of patients was 46 [3457] years, 22 (44%) men and 28 (56%) women. AH developed in 52%, a decrease in eGFR in 42%, along with a decrease in hemoglobin levels and an increase in LDH levels at 2 weeks of therapy. The numbers of schistocytes and platelets significantly decreased by 8 weeks of therapy. Risk factors for impaired renal function during treatment with antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1.73 m2, an increase in D-dimer levels, and a decrease in hemoglobin levels by 8 weeks of treatment. The risk factors for AH during therapy were the initial decrease in eGFR less than 80 ml/min/1.73 m2 and no prophylactic anticoagulant therapy. CONCLUSION: Early signs of nephrotoxicity of antiangiogenic anticancer drugs were a decrease in eGFR and AH. The independent risk factors for nephrotoxicity were the initial decrease in eGFR, an increase in D-dimer levels, and a decrease in hemoglobin levels at 8 weeks of treatment, while the prophylactic use of anticoagulant therapy reduced this risk in our study.

[Role of clustered HER2/neu amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer]. / Rol' klasternoi amplifikatsii gena HER2/neu kak markera 'osoboi' chuvstvitel'nosti k neoad''iuvantnoi anti-HER2-terapii trastuzumabom pri rake molochnoi zhelezy II­III stadii.

OBJECTIVE: To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC). MATERIAL AND METHODS: Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. RESULTS: A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. CONCLUSION: Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.

[Prediction of the effectiveness of the therapy of LUTS/BPH by Serenoa repens extracts].

INTRODUCTION: For the treatment of LUTS/BPH is used a wide range of drugs that patients have to take for a long time. Therefore, it is important to develop methods for predicting long-term results of therapy. The purpose of this work is to evaluate the possibility to predict long-term results of drug therapy of LUTS/BPH using mathematical modeling on the example of treatment with Serenoa repens extract (ESR - Permixon). MATERIALS AND METHODS: For prediction using the methods of predictive analytics of the therapeutic ESR effect in the long term, materials from the open study "Clinical and biological long-term tolerance of a lipidosterolic extract of Serenoa repens (Permixon) in patients with symptomatic benign prostatic hypertrophy" (No. P0048 95 GP 401) were used. The study took place in 1995-1999 in 3 Moscow medical centers: Research Institute of Urology of the Ministry of Health of the Russian Federation, Urological Clinic of the Moscow Medical Academy named after Sechenov and the urology department of Moscow Clinical Hospital No 60. The study included 155 patients aged 52 to 87 years (65.3) who received the drug in 320 mg capsules per day for two years. The target indicators of the prognosis identified key clinical parameters: a decrease IPSS of>25% or>3 points and an increase in Qmax>25% at 12 and 24 months of treatment. When evaluating the results, a binary approach was used: improvement achieved (1), not achieved (0). RESULTS: Using the methods of predictive analytics, mathematical models were built to predict the long-term results of treatment according to the most significant 7 initial criterias (predictors): IPSS; Qmax; average urine flow rate; urination volume, urination time, residual urine volume, prostate volume. For each target field and time interval, mathematical models were built using ensembles from 7 selected machine learning algorithms with the best predictive qualities: BNet; C5.0; SVM; KNN; NNet; CHAID; C&RT. Verification of models on internal randomized samples showed their high prognostic properties: sensitivity 82.4-99.0; specificity 75.0-96.1; AUC 0,864-0,965. CONCLUSION: The potential for effective prediction by the methods of predictive analytics and data mining of the separated results of drug therapy of LUTS / BPH according to the main clinical criteria was demonstrated. It is necessary to continue training and testing the model with the inclusion of new clinical observations in the data set. This approach is applicable to the creation of similar models for predicting the effect of other drugs.

[The clinical laboratory characteristic of primary acute cytomegalovirus infection in non-immunocompromised adult patients].

The purpose of study is the clinical laboratory characteristic of acquired acute cytomegalovirus infection in nonimmunocompromised adult patients. The sampling included 75 patients with acquired acute cytomegalovirus infection admitted to the specialized clinical infection hospital of the Minzdrav of the Krasnodar kraii. The verifcation of diagnosis was implemented using serological tests and polymerase chain reaction. It is demonstrated that males of younger age are most often infected with acute cytomegalovirus infection in the Krasnodar kraii. The disease takes its course in a generalized form. In clinical picture symptoms of intoxication (long-term temperature increasing, weakness), hepatomegaly with increasing of activity of hepatic enzymes, splenomegaly, monolymphocytosis prevail. In most of patients, manifestation of affection of upper respiratory tracts are observed and less frequently - community-acquired pneumonia. The alteration of immune status of patients in dynamics of disease was typical for acute faze of viral infection process with transition to a latent one. At the same time, certain percentage of patients preserved inhibition of neutrophil chain of immunity during re-convalescent period, hence developing menace of bacterial complications. The complex treatment with inclusion of etiotropic anti-viral pharmaceutical Gancyclovir with duration of 8,4±0,4 days resulted in normalization of fever, relief of organic affections and also disappearance of viral DNA from blood. The rate of wrong preliminary diagnoses (85.3%) at referral of patient to hospital testifes complicacy of clinical diagnostic of acute cytomegalovirus infection, conditioned by absence of pathognomonic symptoms under this disease. The last circumstance determines expediency of inclusion into algorithm of examination of patients with unidentifed genesis of fever, hepatosplenomegaly, lymphadenopathy, monolymphocytosis, increasing of activity of hepatic enzymes the analysis of antibodies to antigens of cytomegalovirus (IgM CMV, IgG CMV, avidity of IgG CMV) using enzyme-linked immunosorbent assay and also detection of DNA CMV in blood and urine using polymerase chain reaction technique. The alterations of immune status during re-convalescent period observed in one third of patients determine necessity of their dispensary observation.

[The feasibility of specialized products for nutrition of sportsmen in the preparatory period of the sports cycle].

The nutrition factor is one of the most important in the achievement of high sport results and in maintaining of athlete health along with the methodological and psychological aspects of training. Improving the methods of training in different sports leads to a significant increase in the level of energy expenditure. In order to provide athletes with a large amount of energy, it is advisable to use specialized products with increased nutritive and biological value. Specialists should pay special attention to the scientific justification of composition of special food products (SPP) with consideration of age and gender of athlete, type of sport, the stages of sports activities, training regimes, the qualifications of the athlete and individual level of metabolism. An analytical review of literature on the appropriateness of the application of SPP for athlete nutrition in the preparatory period was conducted to justify the need for further research in this field.

[CLINICAL-EPIDEMIOLOGICAL CHARACTERISTIC OF WEST NILE FEVER IN KRASNODAR REGION].

AIM: Clinical-epidemiological characteristic of West Nile fever on the territory of Krasnodar Region in multi-year dynamics. MATERIALS AND METHODS: Manifestations of epidemic process and clinical symptoms of West Nile fever (WNF) on the territory of Krasnodar Region were analyzed retrospectively from 1988 to 2013. Results of epidemiologic observations wiih inclusion of monitoring of arbovirus circulation, carried out by Prichernomorskaya Station of Plague Control and Centre of Hygiene and Epidemiology in Krasnodar Region were used. Clinical course of verified WNFwas studied in 62 patients, treated in the Specialized Clinical Infectious Hospital ofKrasnodar in 1999-2012. RESULTS: Clinical-epidemiologic characteristic of cases of West Nile fever morbidity on the territory of Krasnodar Region is presented. The presence of acting foci of arbovirus infections was noted. Clinical signs of the disease are established, patients allocated into groups that require examination for West Nile fever. CONCLUSION: Complex of entomologic-virologic monitoring, prophylactic and counter-epidemic measures was determined, that allow to prevent emergence of dangerous epidemiologic manifestations of foci of the disease in the future.

[Use of SPECT-CT for visualization of sentinel lymph nodes in breast cancer patients].

This study was performed in order to determine individual variability of axillary sentinel lymph nodes (SLN) localization in patient with breast cancer (BC). Individual topography of axillary SLN was determined in 182 patients with early BC. All women were candidates for conservative surgical treatment with postoperative radiotherapy. SPECT-CT visualization of SLN started 120-240 min after intratumoral injection of 74-150MBq of 99mTc-radiocolloids. Distribution of axillary SLN was allocated to following subregions: central (C), pectoral (P), apical (AP), lateral (L), subscapular (SSc). SLN visualization by SPECT-CT was successful in 153 cases (84%). AP nodes were detected in 7 patients (5%). SLN were localized on thoracic wall in 34 cases (22%), in the intrapectoral region--in 3 (2%) women. According to axillary levels they were detected on level I--in 149 (97%), level II--15 (10%), level III-- (7.5%) cases.

[Breast cancer with triple-negative phenotype in the Russian patient population. Clinical and morphologic features].

The purpose of this study was to examine the incidence of breast cancer with triple-negative phenotype (TN BC) in the Russian population as well as to compare the clinical and morphological features and outcomes for women with TN BC with other types of breast cancer. We studied a cohort of 499 patients with breast cancer without distant metastases, diagnosed between 2002 and 2011 at N.N.Blokhin Russian Cancer Research Center in Moscow. Triple-negative breast cancers were defined as those that had "negative" level of estrogens and progesteron receptors and were HER2neu negative. 330 (66.2%) of patients has triple negative tumors, 81 (16.2%)--ER and PR negative and HER-2 positive tumors, and 88 (17.6%)--ER and/or ER positive and HER-2 negative tumors. Further was evaluated disease-free and overall survival. 18.5 % of all analyzed patients had triple negative phenotype. Median follow-up was 40.5 months. Characteristic features of the TN BC were: TN breast cancer, compared with other subtypes, characterized by a higher incidence of clinical and morphological features associated with an aggressive course of the disease: the age less than 35 years, grade 3, non- specified invasive histology, high level of Ki-67, the rapid development of the disease, which manifests itself in small terms of the first complaints before the diagnosis. TN BC patients has poorer 5-year overall survival (73.6 + 3.6%) and the 5-year disease-free survival (70.6 + 3.5%), which is significantly lower than the comparable survival of patients with other subtypes of breast cancer (p < 0.001). The results of our study confirm the similarity of majority of clinical and morphological characteristics, course and prognosis of the disease of the Russian population of TN BC patients with those in Europe and the United States.

[Enterovirus non-poliomyelitis infections in Krasnodar region].

AIM: Evaluation of epidemic situation by non-poliomyelitis enterovirus infections in Krasnodar region in multi-year dynamics and characterization of clinical course of enterovirus serous meningitis in hospitalize patients. MATERIALS AND METHODS: Retrospective analysis of non-poliomyelitis enterovirus infection epidemi process manifestations during 2002-2012 in Krasnodar region territory based on data of Center of Hygien and Epidemiology in Krasnodar Region. RESULTS: Clinical-epidemiologic characteristics of enterovirus infections in Krasnodar region are presented. Landscape ofenteroviruses isolated from the environment of some territories of the region and from the biological material of patients with various diseases is demonstrated. Clinical features ofenterovirus meningitis course are characterized. CONCLUSION: Enterovirus transmission b contact route was established to be the most frequent. A lack of pathognomonic symptoms and awareness o physicians of various specialties regarding diagnostics of this infection are the clinical problems of non-po liomyelitis enterovirus diseases.

[Post-vaccination complications during administration of BCG and BCG-M in children of Krasnodar].

AIM: Analysis of frequency and reasons of complications after BCG vaccination in 2008 - 2012 in Krasnodar Region for improvement of prevention measures. MATERIALS AND METHODS: Data on frequency and structure of post-vaccination complications during vaccination against tuberculosis of Centre of Hygiene and Epidemiology in Krasnodar Region and Regional Tuberculosis Hospital in 2008 - 2012 were used. Reasons of the complications were analyzed. RESULTS: During the observation period 16 complications related to immunization with tuberculosis vaccine were noted with frequency index of 5.1 - 40.4 per 100 000 immunized newborns and a tendency of decrease from 2008 to 2012. In the structure of complications cold abscesses (37.5%), lymphadenitis (31.25%) and ostitis (31.25%) occurred at a similar frequency. CONCLUSION: Predominance of cold abscesses in the structure of post-vaccination complications indicates violations in vaccination technologies in maternity hospitals and children's clinics in Krasnodar city, and late periods of post-vaccination ostitis diagnostics - a decrease of epidemiologic awareness of general medical network physicians regarding BCG-vaccination complications, that requires enhancement of immunization control and requalification of personnel carrying it out.

[Results of studies of human dirofilariasis in Russia].

Human dirofilariasis is a pressing health problem in Russia. By 2014, there have been as many as 850 Dirofilaria repens-infested people living in 42 subjects of the Russian Federation. One of the favorable factors for circulation and spread of invasion is a temperature of above +20-24 degrees C; when the latter is maintained during at least 20 days there may be 1.-1.5 circulations of invasion in the carrier and a 2.8-fold increase in transmission intensity. The border ofa dirofilariasis area with a temperate climate is southward to 58 degrees N in European Russia and West Siberia and southward to 50 degrees N in the Far East. The conditions in the human body have been found to be more favorable for the development of Dirofilaria than considered before and allow the helminth to achieve sexual maturity and to propagate. If man has microfilaremia, he may be a source of invasion. It is necessary to examine venous blood by the enrichment method and, if possible, polymerase chain reaction and enzyme immunoassay, which make it possible to establish a diagnosis in occult invasion and to identify a pathogen species.

[Human dirofilariasis: clinical and diagnostic signs and diagnostic methods].

The clinical and diagnostic signs caused by the tissue location and migration of adult Dirofilaria in the human body determine the use of different methods for the diagnosis of dirofilariasis. During their investigations, the authors modified polymerase chain reaction (PCR): they chose and synthesized primers and selected amplification regimens for them and obtained agarose gel bands that corresponded to PCR fragment length nucleotide sequences that were equal to 245 bp for D. (N.) repens and 656 bp for D. immitis. There was 100% agreement in the results of PCR and microscopic examination of sera from 32 dogs and 1 female patient with low parasitemia and in the blood nucleotide sequence characteristic of D. repens.

[SPECT-CT in the diagnosis of metastatic skeletal lesion].

The aim of this study was to compare the diagnostic capabilities of SPECT-CT and planar osteoscintigraphy with 99m-Tc-labeled phosphates in cancer patients. There were examined 227 patients with various primary malignancies (mean age 57 years). Depending on the identified changes in the planar study patients were divided into four groups: I--no abnormalities (n = 62), II--benign changes (n = 67), III--suspected metastatic lesion (n = 41), IV--metastatic lesion (n = 57). The use of SPECT-CT in group I revealed metastatic lesion in 7 (11%) patients, in 15 (24%) patients there were additionally found benign focal changes in the skeleton. In group II metastases were found in 4 (6%) patients; it was not possible to exclude secondary lesion in 3 (4%) patients. In group III suspected metastatic lesion was excluded in 29 (71%) and confirmed in 7 (17%) patients. In group IV in 14 (25%) patients there were found non-tumor changes, the nature of the changes has not been found in 2 (4%) patients. As a result, SPECT-CT with 99m-Tc-labeled phosphates is more informative method of diagnosis of metastatic skeletal lesion than planar osteoscintigraphy. SPECT-CT application resulted in changes of conclusions of the planar scintigraphy about the nature of bone pathology in 67 (30%) cancer patients. However, in 4% the recognition of the nature of changes in the skeleton has failed.

[Role of single-photon emission-computed tomography and x-ray computed tomography in diagnosing lymphatic metastases in patients with non-small cell lung cancer].

Single photon emission tomography (SPECT) with 99mTc-MIBI was performed after conventional staging in 83 operated non-small cell lung cancer (NSCLC) patients. Diagnostic results of SPECT and conventional computerized tomography (CT) staging were validated by histological examinations of operation material. According to histological verification 35 of 83 evaluated patients had lymph node (LN) invasion by NSCLC. SPECT detected LN involvement in 28 of these 35 patients and was false positive in additional 16 patients. Pneumonia or atelectasis were detected in 12 of 16 patients with false positive SPECT results. Sensitivity (Sen), specificity (Sp), accuracy (Ac), positive (PPV) and negative (NPV) predictive values of SPECT in diagnosis of LN invasion by NSCLC was as follows: 80%, 66%, 72%, 65%, 82%. Diagnostic accuracy of CT for detection of LN involvement was inferior to SPECT: Sen--71%, Sp--62%, Ac--66%, PPV--58%, NPV--75%. Combination of SPECT and CT data offer promising solutions with Sen reached 94% or high Sp which in patients without atelectasis or pneumonia can reach 96%.

[The acquired overt cytomegalovirus infection (primary form and reactivation) in adult immune safety patients].

The analysis was applied to clinical course of disease in 102 patients with acquired overt cytomegalovirus infection (75 patients with primary form, 27 patients with reactivation). The primary form of acquired overt cytomegalovirus infection was identified on the basis of detection in enzymoimmunoassay of CMV-lgM under negative CMV-IgG or CMV-IgM and CMV-IgG with avidity less that 50%. The reactivation was diagnosed under identification of CMV-IgG with avidity 50% and more with low indicators of CMV-IgM. The acquired overt cytomegalovirus infection occurs more often in males of young age and proceeds mainly in generalized medium severe form with fever, intoxication and hepatosplenomegaly. The clinical differences are limited by higher rate of generalized forms of disease, febrile fever, weakness, hepatomegaly with increasing of activity of aminotransferase of blood serum, manifestation of signs of affection of respiratory tracts and increase of number of atypical mononuclear leukocytes of peripheral blood in patients with primary form of acquired overt cytomegalovirus infection as compared with reactivated infection.

[The use of SPECT-CT with 99mTc-labeled phosphates in patients with suspected skeletal metastases in planar bone scintigraphy].

We assessed the diagnostic capabilities of SPECT-CT in patients with unclear and suspicious on the secondary lesion with bone scintigraphy background in planar mode (227 patients (mean age - 57 years) with various primary malignancies). All patients underwent planar scintigraphy with 99mTc-labeled phosphates in the "whole body" mode and then - bizonal single-photon-emission computed tomography combined with X-ray computed tomography (SPECT-CT). In patients with the presence of lesions in the skeleton, suspicious on metastases, there was conducted comparison with the data of SPECT-CT. During planar investigation the suspicion on metastases was detected in 41 patients (18%). The use of SPECT-CT allowed excluding metastases in 29 (71%) and confirmed in 7 (17%) of them. In 5 (12%) cases the nature of the changes remained unclear. Thus, in cancer patients with revealed by planar bone scintigraphy unclear or suspicious for metastatic foci in the skeleton, the use of SPECT-CT allowed in most cases (88%) to clarify the nature of these changes.