[Focus ultrasound for cardiology practice. Russian consensus document].

This document is a consensus document of Russian Specialists in Heart Failure, Russian Society of Cardiology, Russian Association of Specialists in Ultrasound Diagnostics in Medicine and Russian Society for the Prevention of Noncommunicable Diseases. In the document a definition of focus ultrasound is stated and discussed when it can be used in cardiology practice in Russian Federation.

The variability of soils and vegetation of hydrothermal fields in the Valley of Geysers at Kamchatka Peninsula.

The picturesque and high conservation value thermal landscapes of the Valley of Geysers feature endothermal (heated by endogenous fluids) soils which support endangered and unique species. However, such soils have not been distinguished as a separate taxon within most classification systems. In this study, we described the soil morphology at macro-, meso- and micro-scales, chemistry, mineralogy and vegetation of these landscapes as they are affected by the steam-heated acid-sulfate waters. The studied catenary sequence from exothermal (non-heated) to endothermal soils was characterized by decreasing contents of soil organic carbon, sand fraction, essential nutrients (Ca, K, Mg, Mn and Si), increasing soil acidity, amounts of fine particle-size fractions and contents of trace elements (Al, As, Co, Cr, Cu, Fe, Pb, Ti and V) as well as the development of sodium-sulfate salinity, kaolinization and ferrugination. In phytocenoses supported by endothermal soils, species of order Rosales and Asparagales were overrepresented among obligate and facultative thermophytes respectively, and species of order Poales were underrepresented among facultative thermophytes in relation to the flora of the Valley of Geysers. Phytocenoses on the non-heated Andosols were enriched in Polypodiopsida species. The results of our comparative analysis of the thermally-induced variability in the soils and vegetation contribute to the general understanding of mineralogical, bio-abiotic and biological systems affected by steam-heated acid-sulfate waters. We hope that our findings will provide a basis for future transdisciplinary studies of the influence of steam-heated waters of a hot spring on the thermal landscapes.

[The role of diastolic transthoracic stress echocardiography with incremental workload in the evaluation of heart failure with preserved ejection fraction: indications, methodology, interpretation. Expert consensus developed under the auspices of the National Medical Research Center of Cardiology, Society of Experts in Heart Failure (SEHF), and Russian Association of Experts in Ultrasound Diagnosis in Medicine (REUDM)].

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is associated with certain difficulties since many patients with HFpEF have a slight left ventricular diastolic dysfunction and normal filling pressure at rest. Diagnosis of HFpEF is improved by using diastolic transthoracic stress-echocardiography with dosed exercise (or diastolic stress test), which allows detection of increased filling pressure during the exercise. The present expert consensus explains the requirement for using the diastolic stress test in diagnosing HFpEF from clinical and pathophysiological standpoints; defines indications for the test with a description of its methodological aspects; and addresses issues of using the test in special patient groups.

Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.

Reactivation of tumor-suppressor p53 for targeted cancer therapy is an attractive strategy for cancers bearing wild-type (WT) p53. Targeting the Mdm2-p53 interface or MdmX ((MDM4), mouse double minute 4)-p53 interface or both has been a focus in the field. However, targeting the E3 ligase activity of Mdm2-MdmX really interesting new gene (RING)-RING interaction as a novel anticancer strategy has never been explored. In this report, we describe the identification and characterization of small molecule inhibitors targeting Mdm2-MdmX RING-RING interaction as a new class of E3 ligase inhibitors. With a fluorescence resonance energy transfer-based E3 activity assay in high-throughput screening of a chemical library, we identified inhibitors (designated as MMRis (Mdm2-MdmX RING domain inhibitors)) that specifically inhibit Mdm2-MdmX E3 ligase activity toward Mdm2 and p53 substrates. MMRi6 and its analog MMRi64 are capable of disrupting Mdm2-MdmX interactions in vitro and activating p53 in cells. In leukemia cells, MMRi64 potently induces downregulation of Mdm2 and MdmX. In contrast to Nutlin3a, MMRi64 only induces the expression of pro-apoptotic gene PUMA (p53 upregulated modulator of apoptosis) with minimal induction of growth-arresting gene p21. Consequently, MMRi64 selectively induces the apoptotic arm of the p53 pathway in leukemia/lymphoma cells. Owing to the distinct mechanisms of action of MMRi64 and Nutlin3a, their combination synergistically induces p53 and apoptosis. Taken together, this study reveals that Mdm2-MdmX has a critical role in apoptotic response of the p53 pathway and MMRi64 may serve as a new pharmacological tool for p53 studies and a platform for cancer drug development.

"Donut's shape" radiosurgical treatment planning for large cystic metastatic brain tumors.

BACKGROUND: Radiosurgical management of large cystic metastatic brain tumors represents a significant challenge. Nevertheless, modified dose planning has shown beneficial results in such cases. METHOD AND RESULTS: "Donut's shape" radiosurgical treatment planning is based on the chain-like application of multiple, small-sized isocenters for selective coverage of the contrast-enhancing tumor capsule and minimal irradiation of the central cystic area. Such an approach was used for the management of large cystic intracranial metastases, which were not accompanied by a significant mass effect and did not require immediate volume reduction. Treatment was done using Leksell Gamma Knife model C with automatic positioning system. The majority of treated lesions showed significant shrinkage after radiosurgery and no major complications were met. CONCLUSION: Large cystic metastatic brain tumors may be successfully treated with gamma knife radiosurgery alone using the proposed "donut's shape" dose planning with coverage of the contrast-enhancing tumor capsule by multiple small-sized isocenters.

[Comparison of transthoracic, transesophageal, and intracardiac echocardiography sensitivity for guiding transseptal puncture during radiofrequency ablation in the left atrium].

The paper contains comparison of sensitivity and rates of false negative results of transthoracic (TT), transesophageal (TE), and intracardiac (IC) echocardiography (echoCG) during transseptal puncture in the run of the procedure of radiofrequency ablation of atrial fibrillation. In the work fulfilled we analyzed results of 208 echocardiographical intraprocedural investigations conducted with the aim of visualization of interatrial septum (IAS) during transseptal puncture. TT, TE and IC echoCG were carried out in 32, 26, and 150 cases, respectively. Phenomenon of IAS stretching was visualized by TT echoCG in 2 (6%) cases (sensitivity 6.7%). At TE tenting phenomenon was verified in 20 patients (20%) (sensitivity 86.9%). Puncture of IAS was carried out under IC echoCG control in 127 patients. Puncture was made in the center of thin portion of IAS (in the region of fossa ovalis), in its upper and lower portions in 65, 28, and 15.7% of cases, respectively. Sensitivity of IC echoCG was 98.4%. Rate of false positive results reached 92.8, 13.04 and 1.5% for TT, TE and IC echoCG, respectively. At present IC echoCG is most sensitive and safe ultrasound technique for verification of optimal positioning of the system for conduct of transseptal puncture in the region of IAS in comparison with TT and TE echoCG.

[Compulsory hospitalization of non-compliant patients with tuberculosis].

The procedure and results of forced treatment per curiam were analyzed in 584 bacteria-discharging persons registered as Group 1 patients to be examined in the tuberculosis facilities of the Kemerovo Region in 2004 to 2007. If a package of measures for forcing the patient to be treated is ineffective, a phthisiatrician draws up documents for court. By the decision of the court, the patient is conveyed by justice officers to a tuberculosis hospital. Judicial practice provides a means of substantially enhancing the efficiency of treatment in this socially compromised group of patients with predominantly destructive processes. Among those who had voluntarily come to the hospital just before or after sentence pronouncement, bacterial discharge cessation and decay cavity closure were achieved in almost 90% of cases; clinical resolution was observed in two thirds. At the same time, there is a group of patients, in whom the existing system of measures has proven to be ineffective. There are serious gaps in the legislation of the Russian Federation, which impede the bringing of patients with tuberculosis, the homeless in particular, to compulsory hospitalization. Legislation should be perfected in this area.

Risk factors for regrowth of intracranial meningiomas after gamma knife radiosurgery: importance of the histopathological grade and MIB-1 index.

INTRODUCTION: The influence of histopathological grade and MIB-1 index of intracranial meningioma on the results of its radiosurgical management is not clear. The objective of the present retrospective study was to make an evaluation of these factors along with an analysis of other variables associated with progression-free survival after gamma knife radiosurgery (GKR). PATIENTS AND METHODS: Thirty-four intracranial meningiomas with known detailed histopathological diagnosis were analyzed. Tumors of WHO histopathological grades I, II, and III were diagnosed in 24, 3, and 7 cases, respectively. The median MIB-1 index was 1.3% (range: 0-31.9%). In 14 cases the MIB-1 index was 3.0% and more. In 26 cases the treatment was done at the time of tumor recurrence. Median volume of the neoplasm at the time of GKR was 4.1 mL (range: 0.4-43.1 mL). Median marginal dose was 12 Gy (range: 8-19 Gy). Median length of follow-up constituted 63 months (range: 19-132 months). RESULTS: Actuarial progression-free survival at 1, 3, 5, and 10 years constituted 100, 94, 83, and 58%, respectively. Histopathological grade II or III (p<0.0001), MIB-1 index 3% and more (p=0.0004), and non-skull base location (p=0.0026) of the tumor showed negative associations with progression-free survival in multivariate analyses. Actuarial progression-free survival at 5 years after GKR for benign and non-benign meningiomas constituted 100 and 45%, respectively (p<0.0001). CONCLUSION: Radiosurgery is a highly effective management option for benign intracranial meningiomas, but growth control of non-benign ones is significantly worse. It requires close neuroradiological follow-up and necessitates the search for modified treatment strategies.

Dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain tissue after stereotactic radiosurgery: a serial proton magnetic resonance spectroscopy study.

The present study evaluated the dynamics of metabolic changes in intracranial metastases and distant normal-appearing brain after stereotactic radiosurgery (SRS). Forty neoplasms were evaluated with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) both before and after treatment. From one to six examinations (median, 3) were done in each individual case during follow-up. At the time of each investigation additional (1)H-MRS was obtained from the normal-appearing brain distant from the radiosurgical target. Investigated metabolites included N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr), and mobile lipids (Lip). Within the first month after SRS responded tumors showed a statistically significant increase in NAA/Cho ratio, and decrease of Cho content and Lip-to-normal brain Cr (nCr) ratio. By contrast, statistically significant metabolic alterations were not detected in stabilized tumors. Statistically significant volumetric and metabolic changes were not marked between three and 12 months after treatment in non-progressing lesions. Alternatively, decrease of NAA/Cho ratio, NAA content and Cr content, and increase in Lip/nCr ratio and Cho content were evident in progressive neoplasms, and subtle metabolic alterations could be revealed even before the increase in the lesion volume. Metabolic characteristics of normal-appearing brain distant from the radiosurgical target did not show statistically significant changes within the first year after treatment. In conclusion, additional use of serial (1)H-MRS during follow-up after SRS for intracranial metastases permits detailed evaluation of the metabolic tumor response and may be potentially helpful for early prediction of recurrence.

Low-grade glioma on stereotactic biopsy: how often is the diagnosis accurate?

The objective of the present study was an evaluation of the incidence and risk factors for erroneous histopathological diagnosis of low-grade glioma after stereotactic biopsy. Twenty-eight tumors diagnosed as low-grade glioma after stereotactic biopsy and surgically resected thereafter were analyzed. There were 13 astrocytomas, 7 oligodendrogliomas, and 8 mixed gliomas. All neoplasms had a lobar location. Seven tumors had contrast enhancement on MRI. The number of tissue samples obtained during stereotactic biopsy was one in 19 cases, two in 4, and three or more in 5. Complete diagnostic agreement in tumor typing and grading after stereotactic biopsy and surgical resection was attained in 10 cases (36%). Agreement in tumor typing was marked in 16 cases (57%). Erroneous typing was more frequent in tumors with an MIB-1 index of less than 3% (P = 0.0629) and mixed gliomas (P = 0.0801). Overgrading of WHO grade I tumors was marked in 3 cases (11%) and undergrading of WHO grade III gliomas in 8 cases (28%). Tumor undergrading was more frequent in cases with an MIB-1 index of more than 3% (P = 0.0045). The MIB-1 index detected after stereotactic biopsy was nearly always lower compared with those established after surgical resection (P < 0.0001). In conclusion, the histopathological diagnosis of low-grade glioma established after stereotactic biopsy is associated with a substantial risk of inaccuracy. Tumors with low proliferative activity and mixed gliomas are especially susceptible for erroneous tumor typing. Undergrading of high-grade gliomas may be suspected if the MIB-1 index in the tumor specimen constitutes more, than 3%.

Advanced computer-aided intraoperative technologies for information-guided surgical management of gliomas: Tokyo Women's Medical University experience.

The availability of the intraoperative MRI and real-time neuronavigation has dramatically changed the principles of surgery for gliomas. Current intraoperative computer-aided technologies permit perfect localization of the neoplasm, precise estimation of its volume, and clear definition of its interrelationships with the eloquent brain structures. This allows maximal tumor resection with minimal risk of postoperative disabilities. Under such conditions the medical treatment has become significantly dependent on the quality of the provided information and can be designated as information-guided management. Therefore, appropriate management of the wide spectrum of the intraoperative medical data and its adequate distribution between members of the surgical team for facilitation of the clinical decision-making is very important for attainment of the best possible outcome. Further progress in advanced neurovisualization, robotics, and comprehensive medical information technology has a great potential to increase the safety of the neurosurgical procedures for parenchymal brain tumors in the eloquent brain areas.

[The experience of the use of intracardiac echocardiography during puncture of atrial septum].

We analyzed results of 175 intracardiac ultrasound studies (ICUS) in 113 men (mean age 54,6 +/- 11,0 years) and 62 women (mean age 49,7 +/- 8,9 years) with atrial fibrillation (n=146) and WPW syndrome (n=29). ICUS was used for guidance of catheters or electrodes from right to left atrium through atrial septum in 160 procedures of radiofrequency ablations for atrial fibrillation (n=146) or WPW syndrome (n=14). Complications of transseptal puncture developed in 4 patients (2,7%) with atrial fibrillation. There were no procedure related deaths. In all cases ICUS allowed to visualize interatrial septum and its thinnest part. Thus ICUS facilitates transseptal approach to the left atrium, provides lowering of risk of dangerous complications, and allows real time monitoring of possible intraprocedural complications.

Ossified frontosphenoorbital meningioma en plaque, mimicking extensive hyperostosis.

Small intratumoral calcifications are often seen within meningioma, but ossification of the whole neoplasm is very rare. The case of an ossified frontosphenoorbital meningioma en plaque is presented. The radiological appearance resembled extensive hyperostosis extending from the anterior clinoid process to the cerebral convexity and falx cerebri. It is possible that, in some cases of meningioma, the identified "hyperostosis" represents partial ossification of the tumor itself.

Low-dose gamma knife radiosurgery for cavernous sinus hemangioma: report of 3 cases and literature review.

Optimal management of cavernous sinus hemangiomas remains unclear. Total microsurgical removal of these neoplasms may be extremely difficult due to their rich vascularization. Three cases of cavernous sinus hemangioma treated with low-dose Gamma Knife radiosurgery are presented. Marginal dose varied from 10 to 13 Gy. Treatment planning and radiation dosimetry were done with a goal of conformal and selective coverage of the lesion with 50% prescription isodose line using multiisocenter technique. In all cases significant shrinkage of the neoplasm was marked at 3 months after treatment. Mean volume reduction at 12 months after radiosurgery was 60% (range: 45-75%). In all patients the shrinkage of the neoplasm was accompanied by notable improvement of the preexistent oculomotor nerve palsy. No radiosurgery-related complications were met during follow-up. In conclusion, low-dose Gamma Knife radiosurgery seems to be very effective for management of cavernous sinus hemangiomas, and can be considered as a treatment modality of choice for these lesions.

[Impact of procedures for identifying patients on the pattern of a tuberculous process and the efficiency of treatment].

The results of examination and treatment were studied in 3637 new cases of pulmonary tuberculosis. A total of 1879 cases were detected at prophylactic examinations (Group 1) and 1758 cases were identified when they resorted to doctors for complaints (Group 2). Circumscribed and benign existing forms of tuberculosis were prevalent in patients at prophylactic examinations. At the same time tuberculosis was accompanied by destruction in a third of cases and by bacterial excretion in half the cases. On applying to the physicians for complaints, the patients were found to have mainly a process with destructions and bacterial excretion and the proportion of acutely progressive forms of tuberculosis was also considerable. In Group 1, treatment showed a much higher efficiency than in Group 2. Deaths from tuberculosis among the new cases were frequently observed in Group 2 and much less frequently in Group 1. Their cause was generally acute tuberculosis.

Differentiation of High-Grade and Low-Grade Gliomas Using Pattern Analysis of Long-Echo Single-Voxel Proton Magnetic Resonance Spectroscopy ((1)H-MRS).

The usefulness of proton magnetic resonance spectroscopy ((1)H-MRS) for glioma grading is not clear, particularly due to the absence of standard criteria for data analysis. Previously we had developed an original classification of the pathological (1)H-MRS spectra based on the identification of the predominant metabolite peak, N-acetylaspartate (NAA) for Type I, choline-containing compounds (Cho) for Type II, and mobile lipids (Lip) for Type III, and presence or absence of other metabolite peaks: lactate (Lac), Lip, or Cho. The present study evaluated the effectiveness of this classification in grading of previously non-treated gliomas. A total of 38 low-grade and 33 high-grade neoplasms were investigated. Four tumors had (1)H-MRS spectra Type I, and all of those were low-grade. Three tumors had (1)H-MRS spectra Type III, and all those were glioblastomas. Fifteen tumors with (1)H-MRS spectra Type II had a Lip/NAA ratio more than 1 (Type II C with moderate elevation of lipids), and 12 of those neoplasms were high-grade. The differences in distribution of high-grade and low-grade gliomas among another 49 gliomas with (1)H-MRS spectra Type II did not depend on the presence of Lac and/or Lip peaks, and in this subgroup NAA/Cho ratio was also evaluated. Inclusion of both characteristics (type of the (1)H-MRS spectrum and NAA/Cho ratio with defined cut-off level of 0.6) into the diagnostic algorithm yielded 72% diagnostic accuracy (95% confidence interval: 62%-82%) in discriminating high-grade and low-grade neoplasms. In conclusion, pattern analysis of the pathological (1)H-MRS spectra using the proposed classification along with evaluation of NAA/Cho ratio might be helpful for non-invasive glioma grading.

Metabolic characteristics of intracranial metastases, detected by single-voxel proton magnetic resonance spectroscopy, are seemingly not predictive for tumor response to gamma knife radiosurgery.

Metabolic characteristics of intracranial metastases, detected with proton magnetic resonance spectroscopy (1H-MRS) have known associations with clinical predictors of tumor response to radiosurgery. Therefore, it can be suspected that the metabolic profile of the neoplasm by itself might have some prognostic significance for the outcome after irradiation. Twenty-six intracranial metastases, which underwent metabolic evaluation with single-voxel 1H-MRS before gamma knife radiosurgery (GKR) and were followed for at least 3 months after treatment, were selected for retrospective analysis. The tumors most frequently originated from the lungs (9 cases), breast (7 cases), colon and rectum (5 cases). The average volume of the investigated intracranial neoplasm was 5.4+/-2.0 mL. The average marginal irradiation dose was 18.6+/-2.3 Gy. The mean follow-up after GKR constituted 8.0+/-5.5 months. Tumor response to GKR was identified in 13 cases on average 2.2+/-1.8 months after treatment. Local recurrence was marked in 10 cases on average 8.7+/-4.1 months after treatment. None of the investigated 1H-MRS metabolic parameters of intracranial metastases showed a statistically significant association with the outcome after GKR. The negative results of the present study make doubtful the predictive value of metabolic characteristics of intracranial metastases, detected with single-voxel 1H-MRS, for the outcome after radiosurgery.

[Interdepartmental interaction in the detection and treatment of patients with tuberculosis].

The experience of interdepartmental interaction in solving the problem of tuberculosis in the Kemerovo Region has been analyzed. The region's administration has strengthened the material-and-technical basis of the service. The advisory tuberculosis council has been set up. Territorial interdepartmental commissions have been organized. The level of an intervention with the general medical network (GMN) has been increased. A qualitative sputum test has been carried out for acid-resistant mycobacteria. The Main Board of the Federal Penal Jurisdiction Service (MBFPJS) and the Board of Internal Affairs are attracted to examine social risk-group persons. Strictly uncontrolled chemotherapy for patients with tuberculosis has been introduced on the basis of GMN at the stage of aftercare and by the forces of the Red Cross Committee. Along with the MBFPJS, continuity has been established in the treatment of patients with tuberculosis. Juridical attraction of bacteria-isolating person to treatment has been introduced. The work done has substantially improved the detection and treatment of patients, but there are problems to be solved.

Fatal intratumoral hemorrhage immediately after gamma knife radiosurgery for brain metastases: case report.

Radiosurgical treatment of brain tumors is sometimes considered to be free from significant acute complications or adverse effects. A rare case of fatal intratumoral hemorrhage immediately after gamma knife radiosurgery (GKR) for brain metastasis is reported. A 46-year-old woman with lung cancer complicated by systemic dissemination experienced an acute episode of headache, speech disturbances, and right-side hemiparesis. She had no history of arterial hypertension or coagulation disorders. CT and MRI disclosed multiple brain metastases. The largest tumor, which was located in the left frontal lobe and caused a significant mass effect, was removed microsurgically without any complications. GKR for nine residual metastases was done on the fourth postoperative day. The marginal dose, which corresponded to the 50% prescription isodose line, constituted 20 Gy. No complications were noticed during frame fixation, treatment itself, or frame removal. Fifteen minutes after the end of the GKR session the patient acutely fell into a deep coma. Urgent CT disclosed a massive hemorrhage in the left cerebellar hemisphere in the vicinity of the radiosurgically treated lesion. The patient died 4 days later and autopsy confirmed the presence of intratumoral hemorrhage. In conclusion, GKR for metastatic brain tumors should not be considered as a risk-free procedure and, while extremely rare, even fatal complications can occur after treatment.

Endoscope-controlled removal of intrameatal vestibular schwannomas.

The use of endoscopes for surgery of the cerebellopontine angle tumors is steadily obtaining widespread acceptance. The objective of the present study was a laboratory and clinical evaluation of the safety of the endoscope-controlled microneurosurgical removal of the intrameatal vestibular schwannomas through a retrosigmoid approach. The anatomical investigation was done on formalin-fixed cadaver heads and dry temporal bones. Clinical series included 33 consecutive patients (23 women and 10 men; mean age 50 +/- 15 years). A bayonet-style rigid endoscope with 70 degrees angle of view and 4 mm outer diameter was found to be optimal for observation of the internal auditory canal. Its insertion in the cerebellopontine cistern should be preferably done under control through an operating microscope. Endoscope-controlled manipulations necessitate the use of a special holder system, which provides a stable position of the device and allows bimanual manipulations by the surgeon. A thermographic evaluation did not reveal a significant increase of the local temperature due to use of the endoscope. Use of the endoscope permitted removal of the neoplasm from the most lateral part of the internal auditory canal and identification of the nerve of tumor origin. In total, 28 tumors underwent total removal, and anatomical preservation of the facial nerve was attained in 31 cases. Damage of the facial nerve by the endoscope was met once. In 8 out of 16 patients, who showed serviceable hearing before surgery, this was preserved after tumor removal. In conclusion, endoscope-controlled removal of the intrameatal vestibular schwannomas seems to be a technically feasible, effective and safe procedure. Nevertheless, good equipment and special training are absolutely necessary for attainment of optimal results.