Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis / Anestésicos halogenados vs. hipnóticos intravenosos para sedación a corto y largo plazo en la unidad de cuidados intensivos: un metaanálisis

Objective To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. Design Systematic review and meta-analysis of randomized and non-randomized trials. Setting ICUs. Participants Critically ill and postoperative patients. Interventions None. Measurements and main results Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60–1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). Conclusions In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened (AU)

Objetivos Evaluar exhaustivamente los estudios revisados por pares que utilizan anestésicos volátiles (AV) o intravenosos (iv) para sedación en unidades de cuidados intensivos (UCI), con la hipótesis de que el tipo de sedación puede tener un impacto en la supervivencia y otros resultados clínicamente relevantes. Diseño Revisión sistemática y metaanálisis de ensayos aleatorizados y no aleatorizados. Ámbito UCI. Pacientes Se incluyeron críticamente enfermos y postoperatorios. Intervenciones Ninguna. Mediciones y resultados principales Los estudios que comparaban los AV vs. los anestésicos iv utilizados en la UCI se buscaron de forma independiente y sistemática. Finalmente, se incluyeron 15 estudios (1.520 pacientes de perfil predominantemente quirúrgico necesitaron sedación de AV durante menos de 96h). El AV no tuvo impacto en la mortalidad por cualquier causa (calidad de los datos probatorios muy baja, Odds Ratio=0,82 [0,60-1,12], p=0,20). Sin embargo, el AV se asoció con una reducción de la duración de la ventilación mecánica (p=0,03) y aumento de los días sin ventilación mecánica (p<0,001). La AV también redujo los niveles postoperatorios de troponina cardíaca (24 horas), el tiempo hasta la extubación (p<0,001) y el despertar (p=0,04). Conclusiones En este metaanálisis, la sedación volátil vs. propofol causó el aumento de los días sin ventilación, la reducción de la duración de la ventilación mecánica, el tiempo hasta la extubación y la liberación de troponina en pacientes de la UCI médica o quirúrgica, mientras que en pacientes de la UCI quirúrgica el tiempo hasta el despertar se acortó (AU)

[The effect of sex hormones and pregnancy on development and progression of uveal melanoma]. / Vliyanie polovykh gormonov i beremennosti na razvitie i progressirovanie uveal'noi melanomy.

The analysis of literature revealed that men experience uveal melanoma (UM) more frequently and with worse prognosis. There are also descriptions of an aggressive course of UM in pregnant women. These facts prompted researchers to analyze the effect of sex hormones and pregnancy on the development and progression of UM. Many years of international experience have refuted the presence of a reliable difference between 5-year survival and 5-year survival without metastases between non-pregnant women with UM and pregnant women with UM. That data is regarded as level 3 evidence. The experts have concluded that UM is not a contraindication to current or future pregnancy, and exogenous hormones (oral contraceptives or hormone replacement therapy) do not affect the incidence and prognosis of UM. Publications provide evidence of expression of the receptors of certain sex hormones (ER, ERRα, LH and LHRH) in primary UM, as well as overexpression of the ESR1 and ESR2 genes in UM with poor predictive characteristics. Overall AR mRNA expression in UM was low, but it was higher in epithelial UMs. The fact of expression of estrogen receptors in UM gives grounds to experiment with them as a target for therapy.

[Predicting the probability of development and progression of primary open angle glaucoma by regression modeling]. / Prognozirovanie veroiatnosti razvitiia i progressirovaniia pervichnoi otkrytougol'noi glaukomy metodom regressionnogo modelirovaniia.

Prediction of the clinical course of primary open-angle glaucoma (POAG) is one of the main directions in solving the problem of vision loss prevention and stabilization of the pathological process. Simple statistical methods of correlation analysis show the extent of each risk factor's impact, but do not indicate the total impact of these factors in personalized combinations. The relationships between the risk factors is subject to correlation and regression analysis. The regression equation represents the dependence of the mathematical expectation of the resulting sign on the combination of factor signs. PURPOSE: To develop a technique for predicting the probability of development and progression of primary open-angle glaucoma based on a personalized combination of risk factors by linear multivariate regression analysis. MATERIAL AND METHODS: The study included 66 patients (23 female and 43 male; 132 eyes) with newly diagnosed primary open-angle glaucoma. The control group consisted of 14 patients (8 male and 6 female). Standard ophthalmic examination was supplemented with biochemical study of lacrimal fluid. Concentration of matrix metalloproteinase MMP-2 and MMP-9 in tear fluid in both eyes was determined using 'sandwich' enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The study resulted in the development of regression equations and step-by-step multivariate logistic models that can help calculate the risk of development and progression of POAG. Those models are based on expert evaluation of clinical and instrumental indicators of hydrodynamic disturbances (coefficient of outflow ease - C, volume of intraocular fluid secretion - F, fluctuation of intraocular pressure), as well as personalized morphometric parameters of the retina (central retinal thickness in the macular area) and concentration of MMP-2 and MMP-9 in the tear film. CONCLUSION: The newly developed regression equations are highly informative and can be a reliable tool for studying of the influence vector and assessment of pathogenic potential of the independent risk factors in specific personalized combinations.

[Significance of anti-myelin basic protein antibodies for ocular hydrodynamic disturbances in primary open-angle glaucoma]. / Rol' antitel k osnovnomu belku mielina v narushenii gidrodinamiki pri pervichnoi otkrytougol'noi glaukome.

The aim of the study was to investigate the significance of anti-myelin basic protein (MBP) antibodies (AB) for ocular hydrodynamic disturbances in primary open-angle glaucoma (POAG). The study was conducted using the enzyme-linked immunosorbent assay (ELISA). The patients included had either high-tension (82 cases), or normal-tension (62 patients) glaucoma (HTG and NTG). In 46.3% of HTG patients and 38.7% of NTG patients, anti-MBP antibodies were lower than in the controls. There were also some cases (12.9%) of increased AB production at NTG onset. According to the canons of immunology, a decrease in anti-MBP antibodies can be explained by their binding to the protein and an increase - by stimulation of AB production through antigen release. In other words, antigen release must precede an increase in antibodies, which, in turn, must be followed by a subsequent decrease. In this aspect, an increase in anti-MBP antibody production at the stage of early hydrodynamic disturbances (NTG) and its decrease at the stage of pronounced changes (HTG) are perfectly natural. The level of anti-MBP antibodies correlated with the following indicators of ocular hydrodynamics: aqueous humor secretion (r=0.20841, p<0.05), intraocular pressure (r=-0.24046, р<0.05), ease of outflow (r=-0, 21552; р<0.05), and Becker's coefficient that reflects dissociation of control mechanisms in the regulation of hydrodynamics (r=-0.21683, p<0.05). The authors came to the conclusion that catalytic antibodies to MBP (also able to cause destruction of the myelin sheath of axons) play an important role in the pathogenesis of open-angle glaucoma. A decrease as well as an increase in anti-MBP antibodies has an unfavorable effect on ocular hydrodynamics. A theory has been put forward that these disorders may be induced by demyelination of peripheral nervous system axons involved in the regulation of intraocular fluid secretion and outflow.

[Primary granulocytic sarcoma of lacrimal gland]. / Pervichnaia mieloidnaia sarkoma sleznoi zhelezy.

The article presents clinical description and instrumental findings (ultrasound examination and multi-slice computed tomography of the orbits) of a rare lacrimal gland tumor, which precedes or concurs with acute myeloblastic leukemia. Due to the low incidence of myeloid (granulocytic) sarcoma, it is not possible to develop a proper algorithm for its diagnosis and treatment. Few descriptions that are available in the literature neither give an idea of the variety of manifestations and the order of organ involvement, nor allow any vital prognosis. Verification of the diagnosis can only be based on immunohistochemical findings of the primary tumor and bone marrow biopsy material. The authors emphasize the importance of combination treatment (radiation therapy of the orbits and chemotherapy) in the prevention of leukemia.

[Contribution of hemodynamic disturbances in magistral vessels to optic neuropathy progression and ocular tension changes in endocrine ophthalmopathy].

AIM: to investigate the contribution of various hemodynamic disturbances in magistral vessels to optic neuropathy (ON) progression and ocular tension changes in endocrine ophthalmopathy (EOP). MATERIAL AND METHODS: A total of 39 patients (78 eyes) with subclinical EOP (clinical activity score, CAS ≤ 2) associated with Graves' disease (n = 32, 64 eyes) or autoimmune thyroiditis (n = 7, 14 eyes) were examined. Orbit echography was performed in all patients. Blood flow was assessed with a Voluson 730 PRO ultrasound diagnostic system ("Kretz", Austria) in triplex mode (B-scan, color Doppler flow mapping in combination with pulse-wave Doppler). Thus obtained hemodynamic parameters in ophthalmic artery, central retinal artery (CRA), central retinal vein (CRV), short posterior ciliary arteries (SPCA), and long posterior ciliary arteries (LPCA) were analyzed. To reveal the role of hemodynamic disturbances in the above mentioned vessels in ON progression and eye pressure maintenance, the patients were divided into 7 groups. Only those eyes, whose peripheral indices were increased by more than 25% of normal values and diastolic blood flow decreased by not less than 25%, were selected for further study. Intraocular pressure changes were evaluated by group mean (Mmean = M ± m mmHg), optic neuropathy progression--by the difference in group mean depth (dB) and number of scotomas between the first and the last visit (6 months of observation). RESULTS: In almost all types of perfusion disturbances, the resultant chronic ocular ischemia causes a decrease in IOP. The only exception, as shown, is simultaneous involvement of CRA, SPCA, and LPCA. The level of blood flow disturbance determines the severity of qualitative and quantitative changes in eyes with EOP-associated ON. The rate of ON progression directly correlates with baseline IOP values on day zero. CONCLUSION: Long-lasting chronic impairment of blood supply of the eyeball leads to reduction in ocular tension and progression of optic neuropathy. Combined perfusion disturbances in CRA and LPCA as well as in CRA, LPCA, and SPCA can be considered a high-risk factor, while SPCA and/or LPCA involvement--a moderate-risk factor.

[Investigation of possible approaches to angiogenesis regulation in vitro with the help of recombinant fragments of angiogenesis inhibitors such as endostatin, tumstatin and PEDF].

Neovascular diseases of visual organ such as age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, thrombosis of central retina vein and its branches, neovascular glaucoma, choroid and retina tumors have the leading positions in the list of ophtalmopatologies that result in blindness and incapacity. The variety of angiostatic medications of applied ophtalmology is scant. The aim of work was to study the possibile approaches to angiogenesis regulation in vitro with the help of recombinant fragments of natural inhibitors of angiogenesis such as endostatin, tumstatin and PEDF (pigment epithelial derived factor), and also theirability to be the base of potentially feasible and pharmacologically active substances. It is determined that endostatin, tumstatin and PEDF, as well as the comparison medication Bevacizumab in vitro have pro-or antiangiogenic influence. The direction of the biological effect depends on the cultivation conditions, peptide concentration in the cultural fluid and stage of angiogenesis.

[Functional tear production indices in thyroid eye disease].

Analysis of functional tear production indices in patients with Grave's disease and thyroid eye disease confirmed lacrimal gland involvement in inflammatory autoimmune process. Close direct correlation was found between tear production and main disease characteristics - severity and activity.

[Recombinant fragment of pigment epithelium-derived factor (44-77) prevents pathological corneal neovascularization].

Pigment epithelium-derived factor (PEDF), a 50 kDa secreted glycoprotein, is among the most potent endogenous inhibitors of angiogenesis. PEDF-derived fragment (44-77) possesses antiangiogenic properties of the full-sized protein and is a potential drug candidate for the treatment of ocular neovascular diseases. In this study we propose an efficient scalable biotechnological method for the production of PEDF (44-77) as part of a fusion protein with SspDnaB intein. The fusion protein was obtained in bacterial E. coli cells in the form of inclusion bodies, solubilized and subjected to autocatalytic cleavage with the release of PEDF (44-77) (yield, 77%). The target peptide was separated from the intein using tangential ultrafiltration. The final purification of PEDF (44-77) was performed by reversed-phase HPLC. The yield of the target peptide (purity, 99%) was 65 mg per 1 liter of culture. Antiangiogenic activity of the obtained peptide was studied in vitro using murine endothelial cells SVEC-4-10. PEDF (44-77) suppressed proliferation of endothelial cells by 53% and inhibited endothelial cell tube formation at the concentration of 1 nM. The ability of the recombinant PEDF (44-77) to block initial stages of angiogenesis was demonstrated using the model of rabbit corneal neovascularization.

[Morphological changes in autoimmune dacryoadenitis associated with thyroid eye disease].

Increase of lacrimal gland (LG) volume was revealed in 1/3 of patients with thyroid eye disease (TED) using visualization methods. Authors show morphological data confirming development of autoimmune process in LG in TED, biopsy samples were studied within 6 hours after exitus. Specific histomorphological characteristics were analysed considering dystrophic and degenerative changes in LG tissue. Quantitative assessment of fibrosis and vascularization extent is determined using fibrosis and vascularization index.

[Experimental rationale for a transscleral approach to thermotherapy for intraocular tumors, by using a photosensitizer].

The authors present the results of an experimental study of the pattern of distribution of laser radiation at a wavelength of 810 nm in the normal and Photosens-photosensitized eye tissues and analyze the distribution of a temperature at the sclera/choroidea/ tumor border during transscleral radiation delivery. To further the goal, the authors have resorted to computer mathematical simulation. In convergent-beam radiation supply, the proportion of a scattered radiation component has been ascertained to be lower in the surface scleral layer than that in the layers adjacent to the choroidea and the base of a tumor. On entering the sclera, a splash of light decreases and power density and radiation-induced heating of the deeply located tissues increase. Thus, the major hyperthermic effects show themselves in the tumor rather than on the sclera.

[Analysis of changes in the accumulation of the photosensitizer Photosens, its elimination kinetics and distribution in the tissues of the eye and eyelids in health and in some tumorous processes].

The authors analyze and present the results of spectroscopic studies into changes in the accumulation of the photosensitizer Photosens, its elimination kinetics and distribution in the tissues of the eye and eyelids, as well as in the tumors that have developed at these sites. The findings allowed the authors to estimate the duration of the agent's persistence in the eye tissues and the time interval associated with the high risk for phototoxic eyelid skin and conjunctival reactions and to determine a possibility of and conditions for photodynamic therapy, as well as the length of hospital stay when the latter was performed.

[Pathomorphological changes in the photosensitized eye tissues after transscleral laser radiation: experimental studies].

The authors analyze the pathological changes occurring in the eye tissues after their prephotosensitization and transscleral laser radiation at a wavelength of 810 nm. These changes involve thrombosis of choroidal vessels, destructions of retinal photoreceptors and sclerocytes, and rupture of collagenous fibers of the deep layers of the sclera with its superficial layers being preserved. These changes were recorded just in the direct radiation area. Their magnitude, depth, and extent were directly correlated with the power of radiation and the diameter of a light splash. In the authors' opinion, the studies performed substantiate a transsceral approach for laser radiation in various abnormalities of the chorioretinal complex.

[Echographic determination of the extent of intraocular tumors].

The capacities of current ultrasound technologies in determining the extent of intraocular tumors were clinically studied. The proposed algorithm of ultrasound study of intraocular tumors allows for not only making the exact measurements of a neoplasm, but also for determining the three-dimensional configuration of an object within the eye.

[Study of a role of the expression of a transmembranous CD117/C-Kit receptor in the progression of uveal melanomas].

The authors studied the expression of the protooncogen receptor involved in the regulation of major cell cycle processes in uveal melanoma. The studies performed by a highly sensitive immunohistochemical technique. The findings have allowed the authors to state that the membranous CD117/C-Kit receptor plays an important role in the progression of uveal melanomas. It is suggested that the use of the new drug Glivec is promising in treating uveal melanoma.

[Study of the expression of embryonal choroidal tissue-specific markers].

The authors used the human embryonal eye to conduct immunohistochemical studies employing the tissue-specific markers of the melanocytic series (HMB45, tyrosinase, melanin A, and MITF) and neuronal differentiation (S100), as well as the markers of intermediate and muscular filaments (vimentin, desmin, smooth muscle actin). The nature of antigen expression was analyzed in different structures and portions of the vascular tract of the eye. The findings unveil the possibility of differentiating the vascular tract tumors of various genesis and their sites, by applying a plate containing the above markers.

[Diagnosis of pigment-free optic tract tumors: clinical and morphoimmunohistochemical aspects].

The authors present the results of comparison of clinical, instrumental and histological, immunohistochemical and electron microscopic data on two pigment-free ciliochoroidal tumors. Differential diagnosis was made at each of the above stages of diagnosis. There is evidence that despite the similarity of the clinical syndrome, the spindle-cell type of the histological structure of both tumors, the latter were of various histogenesis. This was confirmed by the results of immunohistochemical and electron microscopic studies. Retrospective analysis of the data of immunohistochemical and echographic studies revealed the distinctive signs that could differentiate these two types of tumors at the stage of clinical and instrumental diagnosis.

[Differential diagnosis of choroidal tumors on the basis of spatial ultrasound analysis of their angioarchitectonics].

The paper presents the differential diagnostic signs of choroidal tumors, which are revealed by spatial ultrasound analysis of their angioarchitectonics. An algorithm of a study of the angioarchitectonics of choroidal tumors has been developed on the basis of the current ultrasound technologies that can combine B- and 3D-mode grey scale with energy and color Doppler mapping. Fifty-six patients (58 eyes) with various choroidal neoplasms, including 42 patients with choroidal melanomas, 6 with circumscribed choroidal hemangiomas, and 8 (10 eyes) with metastatic choroidal lesion, were examined. Analysis of the results of the study revealed the specific echographic features of each type of a tumor. The proposed procedure of ultrasound analysis makes it possible to expand the spectrum of the analyzed parameters of the angioarchitectonics, to locate spatially, and to trace the association of the neoplasmic vascular bed with the extraocular circulatory system, which is of great importance in choosing an adequate treatment option.