Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer.

Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03-2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators

Assessment of physicians’ and senior medical students’ knowledge in treatment of patients with community acquired pneumonia: Current results of the KNOCAP project

Introduction. Community-acquired pneumonia (CAP) remains one of the most acute problems of bronchopulmonary pathology being the 4th in the mortality structure (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and the 1st among all fatalities from infectious diseases. Thanks to the scientific progress achieved in the antibiotic therapy and vaccine prophylaxis, the death toll has decreased four times compared to its rate during the “pre-antibiotic era“. However, nowadays there is a steadily increasing trend in the pneumonia mortality rate in Russia. The only possible way to increase efficacy of CAP treatment is timely initiated rational antibiotic therapy, considering the possible etiologies, risk factors and the severity of the patient’s condition. Materials and methods. The article represents the results of anonymous prospective surveys within the framework of the KNOCAP multi-centered research project aimed at accessing the knowledge on the fundamental issues in diagnosis and treatment of community-acquired pneumonia. The survey involved 222 students in their fifth- and sixth years in medical institute from Belgorod, Dnepr (Dnipro), Voronezh, Kiev (Kyiv) and Saratov and 110 physicians from Krasnodar, Saratov, Belgorod and Dnepr.Results and discussion. According to the results of the survey, such levels of correct answers were given by doctors and students, respectively: the inadmissibility of antimicrobial therapy (AMT) delay in CAP - 82% and 59%; the main criterion for withholding AMT - 56% and 37%; “sequential therapy” - 61% and 59%. At the same time, only 24% of the students and 23% of the physicians surveyed correctly reported typical mistakes in the treatment of a non-severe CAP with 50% or more accuracy; and in case of initial treatment, the number of correct responses was less than 28% for students and 45% for doctors. Conclusion. The survey showed that both senior medical students majoring in Medical Care and general practitioners had a low level of knowledge in CAP treatment. Hence, curricula need to be adjusted both in medical universities and in health institutions for practitioners in order to inform them and, thus, improve the quality of their knowledge in this field

Comparative assessment of physicians’ and senior medical students’ basic knowledge in treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the most common pathologies of the respira-tory system. This disease ranks third in the group of the main causes of death in the world. The effective treatment of COPD has been developed by today. However, a significant part of physicians has an insufficient amount of education in this matter

Assessment of physicians’ and senior medical students’ knowledge in treatment of patients with community-acquired pneumonia: Current results of the KNOCAP project

Community-acquired pneumonia (CAP) remains one of the most acute problems of bronchopulmonary pathology being the 4th in the mortality structure (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and the 1st among all fatalities from infectious diseases. Thanks to the scientific progress achieved in the antibiotic therapy and vaccine prophylaxis, the death toll has decreased four times compared to its rate during the “pre-antibiotic era“. However, nowadays there is a steadily increasing trend in the pneumonia mortality rate in Russia. The only possible way to increase efficacy of CAP treatment is timely initiated rational antibiotic therapy, considering the possible etiologies, risk factors and the severity of the patient’s condition

Widespread Contribution of Gdf7 Lineage to Cerebellar Cell Types and Implications for Hedgehog-Driven Medulloblastoma Formation

The roof plate is a specialized embryonic midline tissue of the central nervous system that functions as a signaling center regulating dorsal neural patterning. In the developing hindbrain, roof plate cells express Gdf7 and previous genetic fate mapping studies showed that these cells contribute mostly to non-neural choroid plexus epithelium. We demonstrate here that constitutive activation of the Sonic hedgehog signaling pathway in the Gdf7 lineage invariably leads to medulloblastoma. Lineage tracing analysis reveals that Gdf7-lineage cells not only are a source of choroid plexus epithelial cells, but are also present in the cerebellar rhombic lip and contribute to a subset of cerebellar granule neuron precursors, the presumed cell-of-origin for Sonic hedgehog-driven medulloblastoma. We further show that Gdf7-lineage cells also contribute to multiple neuronal and glial cell types in the cerebellum, including glutamatergic granule neurons, unipolar brush cells, Purkinje neurons, GABAergic interneurons, Bergmann glial cells, and white matter astrocytes. These findings establish hindbrain roof plate as a novel source of diverse neural cell types in the cerebellum that is also susceptible to oncogenic transformation by deregulated Sonic hedgehog signaling

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Problems of intellectual property accounting in industrial enterprises in Russia

This paper analyzes important accounting and financial problems associated with identification, determination of the moment of recognition, proper assessment of intellectual properties that are part of intangible assets, determination of their useful life, as well as the search for relevant methods of their depreciation. According to the generalization of theoretical and their own practical experience, the authors propose the approaches to solve these problems, designed to increase the level of reporting reliability for stakeholders, as well as to ensure proper accounting and control of these objects in order to provide their safety and rational use at industrial enterprises

Physicians’ knowledge and preferences in tactics of management and rational pharmacotherapy of arterial hypertension in pregnant women (PHYGEST study)

Introduction: The issues of rational antihypertensive therapy in pregnant women are always extremely relevant, since high blood pressure in a pregnant woman is associated with serious risks for a mother and a fetus. The aim of the study: To determine the knowledge and preferences of physicians in the management of pregnant women with arterial hypertension. Materials and methods: A multicenter study was conducted in 2018–2021 using an anonymous questionnaire among 411 doctors from 8 regions of Russia. Results and discussion: The levels of knowledge and preferences of specialists in the issues of diagnosing and formulating a diagnosis of arterial hypertension and preeclampsia in pregnant women, prescribing basic and additional drugs for the treatment and prevention of hypertension were revealed, and the degree of compliance with the current clinical guidelines was assessed. Conclusion: Due to the insufficient level of knowledge of specialists, it is required to pay increased and special attention to this problem, strengthen control over compliance with clinical guidelines, and introduce it into postgraduate recommendations and continuing education programs