Search

The radioecological situation at the site of the peaceful underground nuclear explosion "Crystal" after removal land cover and installation of the artificial cover of rock from nearby quarry above the epicenter is considered. In 2012 the ambient dose equivalent rate of gamma radiation varied from 0.04 to 0.066 µSv/h, in 2019 the content of radionuclides in soils was (Bq/kg): 90Sr 2.5–5.3, 239,240Pu 0.03–25.4, 137Cs <2.0. In 2018–2020 the activity of radionuclides in surface water was (Bq/dm3): in drains from under the artificial cover 3H 4–12, 90Sr 0.004–0.4, 239,240Pu < 10–6, in local river water 3H 4–10.2, 90Sr 0.004–0.3. At present, the impact of surface drains from the "Crystal" site on the river network is assessed as insignificant. No more than 1/3 of 3H in the local river water comes with precipitation, and the rest of 3H comes from the "Crystal" explosion zone, mainly by an underground route. At least 91–96% of 90Sr in the local river water is due to the "Crystal" explosion: part of it comes from the explosion zone by an underground route, part is washed off from the surface of landscapes. [ABSTRACT FROM AUTHOR]

Comprehensive study of the lagoon terrace section at the apex of Amur Bay has made it possible to identify sharp short-term cooling events at 4450, 2870–2510, 1740–1200, and 680–150 cal BP that are compared to cold events in many regions around the world. The reconstructions are based on the results of diatom, botanical, and palynological analyses. The age–depth model is generated by the Bacon program using radiocarbon dating and tephrostratigraphy. Tephra B-Tm from the caldera-forming eruption of Baitoushan volcano was found in the section. The section selected as a natural archive has its own specifics. In contrast to the mountainous areas and river basins, where the climate became dry 3320–3050 years ago due to a sharp decrease in the intensity of the summer monsoon, coastal lacustrine–boggy sequences developed in constantly waterlogged conditions. This made it possible to identify short-term dry events that correlate well with the global climatic rhythm caused by the decrease in solar radiation. The decrease in moisture was closely related to the influence of the ocean: the intensity of tropical cyclogenesis. The shallowing of the lagoon during the decline of the low-amplitude transgression, intensified by the weakening of the summer monsoon, led to a change from terrigenous to organogenic sedimentation at about 3460 years ago. The cooling event 2870–2510 years ago had the most complex structure with sharp changes in moisture. Change in the course of bog-forming processes around 1740 years ago associated with the activation of floods, which caused periodic flooding of the peat deposits in the vast estuary zone of the Razdolnaya River, led to the disappearance of the tree layer and the development of a grass bog. In general, the regional conditions were dry until the Medieval Warm Period. The response of the landscapes to cooling is identified: the role of broadleaved species in the forest vegetation of the low mountains decreased, and the participation of plants preferring less inundated habitats in the development of local landscapes increased. The Little Ice Age is the exception of the cold events, which was wet and characterized by frequent floods. The meridional transport of moist air masses from the ocean to the continent became more active during that time. [ABSTRACT FROM AUTHOR]

Purpose: Mortality from cardiovascular diseases in Russia is among the highest in the world but little is known about its distribution by socio-demographic factors. We investigated this question in a prospective cohort study based on the Novosibirsk MONICA Project.Method: The cohort consisted of 6485 men and 4919 women aged 25 to 64 years at baseline, examined in 4 surveys in 1984, 1985/86, 1988/89, and 1994/95, and followed up for an average 10.3 (range 3.1-15.2) years. Participants reported their education and marital status in a questionnaire; the information on risk factors was collected in a short medical examination.Results: A total of 836 male and 226 female deaths occurred during the follow up. High education was associated with reduced mortality from all causes, cardiovascular disease, and coronary heart disease in both genders. Age-adjusted relative risk of death from cardiovascular diseases for university vs. primary education was 0.6 (0.4-0.8) in men and 0.4 (0.2-0.8) in women. Adjustment for coronary risk factors and marital status substantially reduced the relative risk in men but not in women. There was no consistent relation between education and stroke. Unmarried men had higher mortality from all causes, cardiovascular and coronary heart disease than married subjects; the increased risk of divorced men was not explained by coronary risk factors or low education. Unmarried women had higher all-cause mortality than married women but associations between marital status and cardiovascular diseases were inconsistent.Conclusion: The educational differences in total and cardiovascular mortality in Russia are of similar direction and magnitude as in western populations. The educational differences in cardiovascular mortality in women and the increased mortality of divorced men were not explained by classical risk factors. [ABSTRACT FROM AUTHOR]

A procedure is proposed for determining the quality of honey by measuring the isotope composition of carbon in the initial honey samples and their protein fractions by mass spectrometry. Seventeen samples of honey harvested in 2014 in various regions of Russia were investigated to identify falsifications with sugars or invert syrups. Using the data on the isotope ratios of δC of initial honey samples and protein fractions, the degree of adulteration of the test honey samples was determined. Concentration of sugar was used as a criterion of adulteration. According to the data obtained, in two samples of honey, the difference between the δC values in the protein fraction and the original honey was more than 1‰, indicating the dilution of these honey samples with cane sugar by more than 7%. It is shown that the isotope composition of honey is not only informative for detecting the adulteration of honey, but also can serve as a kind of marker for the geographical origin of honey. [ABSTRACT FROM AUTHOR]

Background/Objectives:Unhealthy diet has been proposed as one of the main reasons for the high mortality in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) but individual-level effects of dietary habits on health in the region are sparse. We examined the associations between the healthy diet indicator (HDI) and all-cause and cause-specific mortality in three CEE/FSU populations.Subjects/Methods:Dietary intakes of foods and nutrients, assessed by food frequency questionnaire in the Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study, were used to construct the HDI, which follows the WHO 2003 dietary recommendations. Among 18 559 eligible adult participants (age range: 45-69 years) without a history of major chronic diseases at baseline, 1209 deaths occurred over a mean follow-up of 7 years. The association between HDI and mortality was estimated by Cox regression.Results:After adjusting for covariates, HDI was inversely and statistically significantly associated with cardiovascular disease (CVD) and coronary heart disease (CHD) mortality, but not with other cause-specific and all-cause mortality in the pooled sample. Hazard ratios per one standard deviation (s.d.) increase in HDI score were 0.95 (95% confidence interval=0.89-1.00, P=0.068), 0.90 (0.81-0.99, P=0.030) and 0.85 (0.74-0.97, P=0.018) for all-cause, CVD and CHD mortality, respectively. Population attributable risk fractions for low HDI were 2.9% for all-cause, 14.2% for CVD and 10.7% for CHD mortality.Conclusions:These findings support the hypothesis that unhealthy diet has had a role in the high CVD mortality in Eastern Europe. [ABSTRACT FROM AUTHOR]

Background: Moderate alcohol consumption is associated with reduced cardiovascular mortality, but binge drinking is thought to be detrimental. We examined effects of heavy and binge drinking in a population with high rates of binge drinking.Methods: We did a prospective cohort study in Novosibirsk, Russia, in 6502 men aged 25-64 years at baseline who were examined in WHO MONICA (monitoring trends and determinants in cardiovascular disease surveys) in 1985/86, 1988/89, and 1994/95, and in a pilot study in 1984. We assessed alcohol intake and drinking pattern by questionnaire; binge drinking was defined as consumption of 160 g or greater of pure alcohol on a typical occasion. Participants were followed-up for a median of 9.5 years (range 3.1-15.2).Findings: There were 836 deaths in the cohort, 395 of which resulted from cardiovascular diseases. Prevalence of binge drinking at baseline was 16% (n=1005). Adjusted relative risks for binge drinking at least once a month (compared with consumption of <80 g pure alcohol) were 1.05 (95% CI 0.80-1.36) for deaths from all causes, 0.99 (0.66-1.50) for deaths from cardiovascular disease, 1.27 (0.81-1.99) for deaths from coronary heart disease, and 2.08 (1.08-3.99) for death from external causes. Risk of total and cardiovascular mortality was raised in a small group of frequent heavy drinkers (5% [264] of all drinkers); for this group, adjusted relative risks were 1.61 (1.04-2.50) for total mortality and 2.05 (1.09-3.86) for deaths from cardiovascular disease.Interpretation: The risk of death from cardiovascular disease seems to be increased in frequent heavy drinkers, but is not necessarily associated with episodic binge drinking. [ABSTRACT FROM AUTHOR]

The 13 C and 15 N isotope contents in bone collagen were analyzed using bones of the small cave bear Ursus (Spelaearctos) rossicus Borissak, 1930 from localities in the Middle and Southern Urals. The bones date from the last interglacial (MIS 5) and glacial (MIS 3) periods. The bones were from males and females aged 3, 4, and >4 years. Sexual, geographical, and chronological differences in 13 C and 15 N contents were studied. Notable gender, geographic, and chronological differences were observed between samples. In the Middle Urals, females led a more predatory lifestyle than males during the interglacial period, and the trophic niches of males and females converged due to an increase in herbivory during the transition to the glacial period. In the Southern Urals, males led a more predatory lifestyle than in the Middle Urals during the interglacial period. The extent of changes in δ 13 C and δ 15 N values in the Southern Urals during the transition was found to correspond to differences between trophic levels., (© 2023. Pleiades Publishing, Ltd.)

Data on the content of 13 C and 15 N isotopes in the collagen of bones of the Ural cave bear (Ursus (S.) kanivetz Verestchagin, 1973) from the North and Middle Urals were analyzed. The bones date from the first half of MIS 3. The bones of newborn individuals, individuals aged 1 year, males and females aged 2, 3, and 4 years, and older than 4 years were studied. Differences in δ 13 С values between age, sex, and geographical samples are not significant. With age, the value of δ 15 N significantly decreases, which is associated with weaning from milk nutrition to independent nutrition. The proportion of meat food in the diet of adult bears in the Middle Urals was higher than in the diet of adult bears in the North Urals. There are no noticeable differences in isotope signatures between males and females of different ages. The large cave bears of the Urals and Europe had a similar type of diet., (© 2023. The Author(s).)

Objective: The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM)., Methods: Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy)., Results: The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS., Conclusions: Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Background: There are limited data regarding outcomes for patients with gastrointestinal (GI) primaries and brain metastases treated with stereotactic radiosurgery (SRS)., Objective: To examine clinical outcomes after SRS for patients with brain metastases from GI primaries and evaluate potential prognostic factors., Methods: The International Radiosurgery Research Foundation centers were queried for patients with brain metastases from GI primaries managed with SRS. Primary outcomes were local control (LC) and overall survival (OS). Kaplan-Meier analysis was used for univariate analysis (UVA) of prognostic factors. Factors significant on UVA were evaluated with a Cox multivariate analysis proportional hazards model. Logistic regressions were used to examine correlations with RN., Results: We identified 263 eligible patients with 543 brain metastases. Common primary sites were rectal (31.2%), colon (31.2%), and esophagus (25.5%) with a median age of 61.6 years (range: 37-91.4 years) and a median Karnofsky performance status (KPS) of 90% (range: 40%-100%). One-year and 2-year LC rates were 83.5% (95% CI: 78.9%-87.1%) and 73.0% (95% CI: 66.4%-78.5%), respectively. On UVA, age >65 years ( P = .001), dose <20 Gy ( P = .006) for single-fraction plans, KPS <90% ( P < .001), and planning target volume ≥2cc ( P = .007) were associated with inferior LC. All factors other than dose were significant on multivariate analysis ( P ≤ .002). One-year and 2-year OS rates were 68.0% (95% CI: 61.5%-73.6%) and 31.2% (95% CI: 24.6%-37.9%), respectively. Age > 65 years ( P = .006), KPS <90% ( P = .005), and extracranial metastases ( P = .05) were associated with inferior OS., Conclusion: SRS resulted in comparable LC with common primaries. Age and KPS were associated with both LC and OS with planning target volume and extracranial metastases correlating with LC and OS, respectively. These factors should be considered in GI cancer patient selection for SRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

We explored the relationship between the copy number of mitochondrial DNA (mtDNA-CN) and all-cause natural mortality. We examined a random population sample in 2003/2005 ( n = 9360, men/women, 45-69, the HAPIEE project) and followed up for 15 years. Using a nested case-control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer ( n = 371), and a sex- and age-stratified control ( n = 785). The odds ratios (ORs) of death were 1.06 (95%CI 1.01-1.11) per one-decile decrease in mtDNA-CN independent of age, sex, metabolic factors, smoking, alcohol intake and education. The age-sex-adjusted ORs of death in the second and first tertiles of mtDNA-CN vs. the top tertile were 2.35 (95% CI 1.70-3.26) and 1.59 (1.16-2.17); an increased risk was confined to the second tertile after controlling for smoking and metabolic factors. The multivariable-adjusted OR of CVD death was 1.92 (95% CI 1.18-3.15) in tertile 2 vs. the top tertile of mtDNA-CN, and for cancer-related death the ORs were 3.66 (95% CI 2.21-6.05) and 2.29 (95% CI 1.43-3.68) in tertiles 2 and 1 vs. the top tertile. In the Siberian population cohort, the mtDNA-CN was an inverse predictor of the 15-year risk of natural mortality, due to the greatest impact of CVD and cancer-related death. The findings merit attention for exploring further the role of mtDNA in human ageing and the diversity of mortality.

First data on the contents of the 13 C and 15 N isotopes in collagen were obtained for 16 bones of the Ural cave bear Ursus (Spelaearctos) kanivetz Verestchagin, 1973 from the Tayn (Secrets) cave (55°25' N, 57°46' E). The bones are dated to the middle MIS 3 and belonged to males and females of about 2 years, about 3 years, and older than 4 years of age. No considerable difference in isotope signatures was observed between individuals of different ages and different genders. Cave bears were assumed to forage independently on plant food from the second year of life. The δ 13 C and δ 15 N values established for the Ural cave bear are close to the values reported for U. (S.) spelaeus ingressus., (© 2023. Pleiades Publishing, Ltd.)

Objective: to study the association of relative leukocyte DNA telomere length with death from natural causes during a 15-year follow-up in a middle-aged and elderly Siberian population. Study of the association of the relative length of leukocyte telomeres (LTL) with fatal outcomes during a 15-year follow-up of a random population sample formed in 2003-2005 (n=9 360, 45-69 years old, Novosibirsk, HAPIEE project). The main group included the persons died from natural causes (except external) without a previous history of CVD and cancer (n=609); controls were stratified by sex and age (n=799). The analysis of relative LTL at baseline was performed using quantitative real-time PCR. We estimated the odds ratio of all-cause death per 1 decile shortening of LTD as a continuous variable in a multivariable-adjusted logistic regression. The carriers of shorter telomere carriers had an increased risk of death from natural causes over the next 15 years (OR=1,37, 95% CI 1,31-1,44) per decile of LTL decrease, regardless of other factors. The risk coefficients were similar for death from CVD (1,39), cancer (1,42), and other non-external causes (1,51). In studied middle-aged and elderly Siberian (Caucasoid) population cohort the LTL was an independent inverse predictor of the 15-year risk of death from natural causes.

We aimed to analyze the profile of glucose lowering therapy (GLT) in persons with diabetes mellitus type 2 (DM2) in an aging Russian population. A random population sample (n = 3898, men/women, 55−84) was examined in Novosibirsk, during 2015−2018 (HAPIEE Project). The design of the present work is a cross-sectional study. DM2 was defined in those with a history of DM2 receiving GLT, or at a level of fasting plasma glucose (FPG) ≥7.0 mmol/L. The entire DM2 group was included in the analysis (n = 803); of these, 476 persons were taking GLT and were included in the analysis at stage 2. Regular GLT medication intake for 12 months was coded with ATC. In studied sample, the prevalence of DM2 was 20.8%. Among subjects with DM2, 59% of individuals received GLT, 32% did not. Glycemic control (FPG < 7.0 mmol/L) was achieved in every fifth participant with DM2 (35% in those receiving GLT). In frequency of GLT use, biguanides ranked in first place (75%), sulfonylurea derivatives in second (35%), insulins in third (12%), and iDPP-4 in fourth (5%). Among those receiving GLT, 24% used combined oral therapy, and 6% used insulin-combined therapy. In conclusion, in a population sample aged 55−84 examined in 2015−2018, glycemic control was achieved in every fifth participant with DM2, and in every third participant receiving GLT. The proportion of participants using new GLT drugs was small, and there was a lack of HbA1c monitoring for intensive glycemic control.

Background: The association between impaired lung function and mortality has been well documented in the general population of Western European countries. We assessed the risk of death associated with reduced spirometry indices among people from four Central and Eastern European countries., Methods: This prospective population-based cohort includes men and women aged 45-69 years, residents in urban settlements in Czech Republic, Poland, Russia and Lithuania, randomly selected from population registers. The baseline survey in 2002-2005 included 36,106 persons of whom 24,993 met the inclusion criteria. Cox proportional hazards models were used to estimate the hazard ratios of mortality over 11-16 years of follow-up for mild, moderate, moderate-severe and very severe lung function impairment categories., Results: After adjusting for covariates, mild (hazard ratio (HR): 1.25; 95% CI 1.15‒1.37) to severe (HR: 3.35; 95% CI 2.62‒4.27) reduction in FEV1 was associated with an increased risk of death according to degree of lung impairment, compared to people with normal lung function. The association was only slightly attenuated but remained significant after exclusion of smokers and participants with previous history of respiratory diseases. The HRs varied between countries but not statistically significant; the highest excess risk among persons with more severe impairment was seen in Poland (HR: 4.28, 95% CI 2.14‒8.56) and Lithuania (HR: 4.07, 95% CI 2.21‒7.50)., Conclusions: Reduced FEV1 is an independent predictor of all-cause mortality, with risk increasing with the degree of lung function impairment and some country-specific variation between the cohorts., (© 2022. The Author(s).)

Background: Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient's own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock., Methods: A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30-40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA., Results: Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034)., Conclusions: Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management., (© 2022. The Author(s).)

Aim      To analyze frequency and profile of the lipid-lowering therapy (LLT) in patients with dyslipidemia (DLP) and cardiometabolic diseases (CMD) in a population sample aged 55-84 years at the current time (2015-2017).Material and methods  Despite guidelines on DLP treatment and the availability of effective and safe lipid-lowering drugs, control of DPL in primary and secondary prevention of cardiovascular diseases (CVD) is insufficient. Knowledge of the level of pharmaceutical correction of DLP in the Russian population is limited; it requires an LLT assessment in various regions and in a wide age range, and a regular monitoring taking into account changing approaches to the correction of DLP. A random population of men and women aged 55-84 years (n=3 896) was evaluated in Novosibirsk in 2015-2017 (project HAPIEE). A joint DLP category was established as low-density lipoprotein cholesterol (LDL-C) ≥3.0 mmol/l, or total cholesterol (TC) ≥5.0 mmol/l, or triglycerides (TG) ≥1.7 mmol/l, or LLT. The combined group of DLP and CMD included ischemic heart disease (IHD), type 2 diabetes mellitus (DM2), and DLP. Regular LLD treatment for the recent 12 months, excluding the dosage of medicines, was assessed using the Anatomic Therapeutic Chemical (ATC) classification. The conditional control of serum lipids was taken as the achievement of LDL-C &lt;3.0 mmol/l, TC &lt;5.0 mmol/l, and TG &lt;1.7 mmol/l.Results In the study sample, the total prevalence of DLP and CMD was 88 % (82.8 % for men and 91.3 % for women, p&lt;0.001). 48.3% of patients in the IHD group, 35.0% in the DM2 group, 29.4% in the DLP group, and 32.8% in the CMD group took LLT. Control of serum lipids was achieved in 18.3% (37.9 % of patients on LLT) of patients with IHD; 9 % (25.6 % of patients on LLT) of patients with DM2; 7.3 % (24.8 % of patients on LLT) of patients with DLP; and 9.0 % (27.6 % of patients on LLTсреди) in the DLP and CMD group. Women with DM2 and DLP more frequently achieved lipid control than men (p&lt;0.001). 98.7 % of study participants took statins as LLT.Conclusion      In the sample of urban population aged 55-84 years in 2015-2017, 90 % of patients had DLP or CMD, and at least ¾ of them required blood lipid control. The lipid control was achieved in every fifth IHD patient and in approximately 40% of those who took LLT. For DM2 or DLP patients, the lipid control was achieved in every tenth patient and in approximately 25% of those receiving LLT. Frequency of lipid control in IHD patients was comparable for men and women; in DM2 and DLP, men less frequently achieved the lipid control than women. About 70% of patients in the combined DLP and CMD group and more than 50% of IHD patients did not take LLT, which considerably contributed to the insufficient lipid control in primary and secondary prevention of atherosclerotic CVDs in this population.

Background: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management., Methods: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg., Results: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to -3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01)., Conclusion: Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Objective: As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases., Methods: Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed., Results: Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6-28) Gy, and the median tumor volume was 2.45 (range 0.04-45) ml. At a median radiological follow-up of 6 (range 0-156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3-5 toxicities noted., Conclusions: SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.

Background: Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. Methods: From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). Results: We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm 3 (range: 0.003-38.18 cm 3 ), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452, p  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904; p  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945; p  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. Conclusion: The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.