Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index ( r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O 2 /s/10 6 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Pragmatic Evaluation of a Deep-Learning Algorithm to Automate Ejection Fraction on Hand-Held, Point-of-Care Echocardiography in a Cardiac Surgical Operating Room.

OBJECTIVE: To test the correlation of ejection fraction (EF) estimated by a deep-learning-based, automated algorithm (Auto EF) versus an EF estimated by Simpson's method. DESIGN: A prospective observational study. SETTING: A single-center study at the Hospital of the University of Pennsylvania. PARTICIPANTS: Study participants were ≥18 years of age and scheduled to undergo valve, aortic, coronary artery bypass graft, heart, or lung transplant surgery. INTERVENTIONS: This noninterventional study involved acquiring apical 4-chamber transthoracic echocardiographic clips using the Philips hand-held ultrasound device, Lumify. MEASUREMENTS AND MAIN RESULTS: In the primary analysis of 54 clips, compared to Simpson's method for EF estimation, bias was similar for Auto EF (-10.17%) and the experienced reader-estimated EF (-9.82%), but the correlation was lower for Auto EF (r = 0.56) than the experienced reader-estimated EF (r = 0.80). In the secondary analyses, the correlation between EF estimated by Simpson's method and Auto EF increased when applied to 27 acquisitions classified as adequate (r = 0.86), but decreased when applied to 27 acquisitions classified as inadequate (r = 0.46). CONCLUSIONS: Applied to acquisitions of adequate image quality, Auto EF produced a numerical EF estimate equivalent to Simpson's method. However, when applied to acquisitions of inadequate image quality, discrepancies arose between EF estimated by Auto EF and Simpson's method. Visual EF estimates by experienced readers correlated highly with Simpson's method in both variable and inadequate imaging conditions, emphasizing its enduring clinical utility.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Challenges and opportunity in mobility among older adults - key determinant identification.

BACKGROUND: Attention is focused on the health and physical fitness of older adults due to their increasing age. Maintaining physical abilities, including safe walking and movement, significantly contributes to the perception of health in old age. One of the early signs of declining fitness in older adults is limited mobility. Approximately one third of 70-year-olds and most 80-year-olds report restrictions on mobility in their apartments and immediate surroundings. Restriction or loss of mobility is a complex multifactorial process, which makes older adults prone to falls, injuries, and hospitalizations and worsens their quality of life while increasing overall mortality. OBJECTIVE: The objective of the study is to identify the factors that have had a significant impact on mobility in recent years and currently, and to identify gaps in our understanding of these factors. The study aims to highlight areas where further research is needed and where new and effective solutions are required. METHODS: The PRISMA methodology was used to conduct a scoping review in the Scopus and Web of Science databases. Papers published from 2007 to 2021 were searched in November 2021. Of these, 52 papers were selected from the initial 788 outputs for the final analysis. RESULTS: The final selected papers were analyzed, and the key determinants were found to be environmental, physical, cognitive, and psychosocial, which confirms the findings of previous studies. One new determinant is technological. New and effective solutions lie in understanding the interactions between different determinants of mobility, addressing environmental factors, and exploring opportunities in the context of emerging technologies, such as the integration of smart home technologies, design of accessible and age-friendly public spaces, development of policies and regulations, and exploration of innovative financing models to support the integration of assistive technologies into the lives of seniors. CONCLUSION: For an effective and comprehensive solution to support senior mobility, the determinants cannot be solved separately. Physical, cognitive, psychosocial, and technological determinants can often be perceived as the cause/motivation for mobility. Further research on these determinants can help to arrive at solutions for environmental determinants, which, in turn, will help improve mobility. Future studies should investigate financial aspects, especially since many technological solutions are expensive and not commonly available, which limits their use.

Severe Impairment of Microcirculatory Perfused Vessel Density Is Associated With Postoperative Lactate and Acute Organ Injury After Cardiac Surgery.

OBJECTIVE: Resuscitation after cardiac surgery needs to address multiple pathophysiological processes that are associated with significant morbidity and mortality. Functional microcirculatory derangements despite normal systemic hemodynamics have been previously described but must be tied to clinical outcomes. The authors hypothesized that microcirculatory dysfunction after cardiac surgery would include impaired capillary blood flow and impaired diffusive capacity and that subjects with the lowest quartile of perfused vessel density would have an increased postoperative lactate level and acute organ injury scores. DESIGN: Prospective, observational study. SETTING: A single, tertiary university cardiovascular surgical intensive care unit. PARTICIPANTS: 25 adults undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTION: Sublingual microcirculation was imaged using incident dark field microscopy before and 2 to 4 hours after surgery in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Compared with baseline measurements, postoperative vessel-by-vessel microvascular flow index (2.9 [2.8-2.9] v 2.5 [2.4-2.7], p < 0.0001) and perfused vessel density were significantly impaired (20.7 [19.3-22.9] v 16.3 [12.8-17.9], p < 0.0001). The lowest quartile of perfused vessel density (<12.8 mm/mm2) was associated with a significantly increased postoperative lactate level (6.0 ± 2.9 v 1.8 ± 1.2, p < 0.05), peak lactate level (7.6 ± 2.8 v 2.8 ± 1.5, p = 0.03), and sequential organ failure assessment (SOFA) score at 24 and 48 hours. CONCLUSION: In patients undergoing cardiac surgery, there was a significant decrease in postoperative microcirculatory convective blood flow and diffusive capacity during early postoperative resuscitation. Severely impaired perfused vessel density, represented by the lowest quartile of distribution, is significantly related to hyperlactatemia and early organ injury.

Heparin-Induced Thrombocytopenia: A Review for Cardiac Anesthesiologists and Intensivists.

Patients undergoing cardiovascular surgery may be exposed to heparin before surgery, during cardiopulmonary bypass (CPB), or in the immediate postoperative period. For this reason, cardiovascular surgery patients are at increased risk for heparin-induced thrombocytopenia (HIT), occurring in 1 to 3% of patients. The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT, which we will review in detail with a diagnostic algorithm. In addition, we will cover the prevention and treatment HIT.

Composition of ashes from the combustion of solid fuels and municipal waste in households.

In this study, 73 ash samples (comprising 49 ash samples from combustion tests performed in 2017, and 24 ash samples from combustion tests performed during 2014-2016 at the Energy Research Center, Ostrava, Czech Republic) were analysed. Ash samples were obtained via the combustion of various solid fuels, their mixtures with municipal waste (floor coverings, paper, polyethylene terephthalate (PET) briquettes, plastics, and textiles), and municipal wood waste (furniture chipboard, window frames) in household combustion units, such as an overfire boiler, boiler with downdraft combustion, gasification boiler, automatic boiler, and stove. The aim of this study was to determine the composition of representative ash samples from solid fuels and municipal waste and to determine which parameters (metals and halides) were present in the ash analysis after waste incineration. Statistical evaluation of box plots with the determination of the boundaries for outliers and extreme values was performed. Finally, six metals (Sb, Cu, Pb, Sn, Ti, and Zn), together with chlorides, were taken as the indicators of municipal waste incineration in households. The highest value of Sb was 344 mg/kg in plastics + dry beech; the highest value of Cu was 30,500 mg/kg in textiles + black coal (B1); the highest concentration of Pb was 1,360 mg/kg in floor coverings + dry beech; the highest value of Sn was 108 mg/kg in textiles + dry beech; the highest concentration of Ti was 38,200 mg/kg in window frames; the highest value of Zn was 215,000 mg/kg in window frames; and the highest concentration of chlorides was 191,000 mg/kg in floor coverings + dry beech.

Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease.

Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.

Validation study of Doppler-derived transmitral valve gradients compared to near simultaneously obtained directly measured catheter gradients immediately after mitral valve repair surgery.

OBJECTIVE: To evaluate the accuracy of Doppler-derived transmitral valve gradients immediately after mitral valve repair by comparing them with near simultaneously obtained direct catheter gradients. DESIGN: A prospective study. SETTING: A tertiary care medical center. PARTICIPANTS: Twenty elective adult surgical patients presenting for mitral valve repair surgery. METHODS: Mitral valve surgery proceeded in standard fashion except for the use of a smaller than usual left ventricular vent catheter (Medtronic DLP 10 French left heart vent catheter). After completion of the mitral valve repair and subsequent cardiac de-airing, the patient was weaned from cardiopulmonary bypass. Immediately after separation, the study period began. Near simultaneous transmitral Doppler gradients were obtained with directly measured catheter gradients via the vent catheter. RESULTS: While the mean peak gradient difference of 1.1 mmHg was small (p-value 0.18, 95% CI: -0.54 to 2.73 mmHg), the correlation between Doppler and catheter gradient measurements (Pearson correlation coefficient r = 0.54, p = 0.055) only approached statistical significance due to the large variance associated with the small sample size. In all patients with a peak gradient greater than 10 mmHg (4 of the 20 patients), overestimation of catheter gradients by Doppler occurred, with two showing a 62% to 73% discrepancy. In these two cases, there was also evidence for elevated left ventricular end-diastolic pressure (LVEDP) along with high transmitral blood flow velocities. CONCLUSION: Doppler-derived transmitral gradients provide a simple, safe, and reliable measure of the true physiologic transmitral valve gradient. At the same time, it is important to recognize that significant Doppler over-estimation of catheter gradients may occur in patients with elevated Doppler transmitral velocities. The causes of these overestimations are unknown. They may be related to technical recording errors. They may also be related to an inherent weakness in Doppler technology--its inability to account for any distal recovery of pressure, which in a select group of patients could be significant.

Unveiling Seniors' Perception of Mobility: Urbanization, Region, and Physical Activity.

Background: Maintaining mobility is fundamental to active aging, allowing older adults to lead dynamic and independent lives. The perception of mobility among older adults significantly impacts their overall well-being and quality of life. Given the aging population, mobility has become an increasingly pressing issue. Aim: This study focused on the perception of urban neighborhoods, including considerations of urban tissue (crossings and sidewalk maintenance), urban scenes (benches and traffic), and safety (fears and street lighting quality). We investigated the differences in the perception of the surroundings of residences by urban and rural seniors concerning their demographic and social characteristics and environmental determinants. Methods: A quantitative study design utilizing a questionnaire survey was employed. Data were collected mainly through face-to-face interviews in the field (PAPI) and via an online questionnaire (CAWI). The final sample comprised 525 participants. Hypotheses regarding the influence of gender, age, social status, level of physical activity, degree of urbanization, and region on environmental perception were tested using ordinal regression. Results: The hypothesis regarding the dependence of the perception of the surroundings on the level of urbanization was confirmed; that regarding the dependence of the perception of the residence surroundings on seniors' age was not confirmed. The other hypotheses were partially confirmed. For the seven investigated environmental attributes, gender was significant in two cases, social status and physical activity in three cases, and region in four cases. Conclusion: While most studies have focused on urban settings, this study highlights the situation in rural municipalities. Substantially worse pedestrian conditions in availability of pedestrian crossings, benches, and lighting were recognized in rural municipalities versus cities. Understanding the complexity of mobility and the spatial locations relevant for older persons concerning potential barriers and facilitators for mobility aids in planning and adapting neighborhood environments to promote active and healthy aging in place.

Duodenal expression of iron transport molecules in patients with hereditary hemochromatosis or iron deficiency.

Disturbances of iron metabolism are observed in chronic liver diseases. In the present study, we examined gene expression of duodenal iron transport molecules and hepcidin in patients with hereditary hemochromatosis (HHC) (treated and untreated), involving various genotypes (genotypes which represent risk for HHC were examined), and in patients with iron deficiency anaemia (IDA). Gene expressions of DMT1, ferroportin, Dcytb, hephaestin, HFE and TFR1 were measured in duodenal biopsies using real-time PCR and Western blot. Serum hepcidin levels were measured using ELISA. DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post-phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls. The protein expression of ferroportin was increased in both groups of patients but not significantly. Spearman rank correlations showed that DMT1 versus ferroportin, Dcytb versus hephaestin and DMT1 versus TFR1 mRNAs were positively correlated regardless of the underlying cause, similarly to protein levels of ferroportin versus Dcytb and ferroportin versus hephaestin. Serum ferritin was negatively correlated with DMT1 mRNA in investigated groups of patients, except for HHC group. A decrease of serum hepcidin was observed in IDA patients, but this was not statistically significant. Our data showed that although untreated HHC patients do not have increased mRNA levels of iron transport molecules when compared to normal subjects, the expression is relatively increased in relation to body iron stores. On the other hand, post-phlebotomized HHC patients had increased DMT1 and ferroportin mRNA levels possibly due to stimulated erythropoiesis after phlebotomy.

[Statistics in clinical and experimental medicine]. / Statistika v klinické a experimentální medicíne

The paper presents a brief overview of statistical methods used in clinical and experimental medicine, ranging from basic indicators and parameters of descriptive statistics and hypotheses testing (parametric as well as non-parametric methods) to a description of the most frequently used multivariate methods in medical scientific publications, to logistic regression. The paper also describes Principle Component Analysis (PCA), which is one of the methods used to decrease a data dimensionality. The proper use of statistical methods is demonstrated on specific clinical cases.

Influence of co-combustion of unsuitable fuels with standardized fuels in households on CO, OGC, PM, and PAH emissions.

Waste combustion in residential small-scale combustion units is not legal in the Czech Republic or other European Union countries. The resulting gaseous and particulate pollutants expose inhabitants to smells and toxic compounds and may damage their property and health. This study is designed to define the emissions of gaseous and particulate pollutants and determine the influence of municipal waste combustion on emission factors. Different types of solid fuels, municipal wood wastes (window frames, furniture chipboard), and mixtures of solid fuels with municipal wastes (namely, textiles, plastics, PET briquettes comprising a mixture of PET bottles + wood pellets + frying oil, paper, and floor coverings) were combusted in residential combustion units (such as gasification boiler, boiler with down-draft combustion, overfire boiler, and stove). Studies describing such an extensive range of waste samples combusted in different small-scale combustion units have not yet been published. Emission factors (EFs) for products of incomplete combustion (carbon monoxide (CO), organic gaseous compounds (OGC), and polycyclic aromatic hydrocarbons (PAHs) in gaseous and particulate phases) and particulate matter (PM) were within narrow intervals and lowest for standardized wood fuel (dry wood logs only) and 2-4 times higher on average for unsuitable coal samples (coal unsuitable for the particular boiler type used and coal combined with waste), for which values fell within broad intervals.The EFs of pollutants resulting from incomplete combustion (CO, OGC, and 16 PAHtotal) and PM were lowest for standardized wood fuel (dry wood logs only) and almost two or four times higher on average for unsuitable coal fuels (coal unsuitable for the particular boiler type used and coal combined with waste).