Connecting hemosysis and visceral injury during cardiovascular surgery : studies on the causes, effects, and treatment of hemolysis-induced organ injury

Patients who undergo major cardiovascular surgery run a relatively high risk of postoperative complications, such as intestine and kidney damage. This dissertation describes the connection between red blood cell injury (hemolysis), which is often the consequence of the heart-lung machine and blood transfusions during surgery, and the development of intestine and kidney injury after the operation. The various studies gathered in this dissertation show that patients that experience more hemolysis also develop more intestine and kidney injury. Because it is possible to treat the consequences of hemolysis, the results of this dissertation can contribute to the prevention of complications after cardiovascular surgery

Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10-hydroxynortriptyline serum levels-A prospective pharmacokinetic study

The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10-hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50-150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges

Расчет бокового магнитного сопротивления электромагнитных молотков

Hemolysis is an inevitable side effect of cardiopulmonary bypass resulting in increased plasma free hemoglobin that may impair tissue perfusion by scavenging nitric oxide. Acute kidney injury after on-pump cardiovascular surgery arises from a number of causes and severely affects patient morbidity and mortality. Here, we studied the effect of acute hemolysis on renal injury in 35 patients undergoing on-pump surgical repair of thoracic and thoracoabdominal aortic aneurysms of whom 19 experienced acute kidney injury. During surgery, plasma free hemoglobin increased, as did urinary excretion of the tubular injury marker N-acetyl-β-D-glucosaminidase, in patients with and without acute kidney injury, reaching peak levels at 2 h and 15 min, respectively, after reperfusion. Furthermore, plasma free hemoglobin was independently and significantly correlated with the urine biomarker, which, in turn, was independently and significantly associated with the later postoperative increase in serum creatinine. Importantly, peak plasma free hemoglobin and urine N-acetyl-β-D-glucosaminidase concentrations had significant predictive value for postoperative acute kidney injury. Thus, we found an association between increased plasma free hemoglobin and renal injury casting new light on the pathophysiology of acute kidney injury. Therefore, free hemoglobin is a new therapeutic target to improve clinical outcome after on-pump cardiovascular surgery

Породы песчаники – редкие материалы высокой крепости – уникальные фрикционные материалы

Розглядаються питання при підготовці до відпрацювання пологих вугільних пластів на великих глибинах в умовах шахти «Довжанська Капітальна» ТОВ "ДТЕК Свердловантрацит". Проведено дослідження вміщуючих підготовчу виробку порід. Запропоновано можливості проектування комплексного видобутку супутніх корисних компонентів при підготовці Антрацитівського пластів до видобутку.The questions in preparation for mining of shallow coal seams at great depths in the mine "Dolzhanskaya Capital" LLC "DTEK Sverdlovantratsit." Investigations of host rocks of underground working. Suggested the possibility of designing an integrated co-production of useful components in preparation Antratsitovskogo of flat seam to production

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

Introduction: The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied. Methods: Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation. Results: Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P &lt; 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P &lt; 0.001 and P &lt; 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations. Conclusion: These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.Annadal Foundation of the Maastricht University Medical CenterAnnadal Foundation of the Maastricht University Medical Cente

Medicatiescreening met Beers-criteria en STOPP/START-criteria bij de oudere patiënt: associatie tussen potentieel ongewenst geneesmiddelengebruik en geneesmiddelgerelateerde ziekenhuisopnamen

OBJECTIVE To assess the risk of medication-related hospital admissions associated with inappropriate medication use applying the Beers and the STOPP/START criteria. There are multiple screening methods to detect and reduce potentially inappropriate medication [PIM] and prescribing omissions (PPOs). Whether this will result in less medication-related hospitalisations is unknown. DESIGN A nested case-control study was conducted with a subset of patients of the Hospital Admissions Related to Medication (HARM) study. METHODS Cases were defined as patients ≥65 years with a potentially preventable medication-related hospital admission. For each case one control was selected, matched on age and sex. The primary determinant was defined as the presence of one or more PlMs and/or PPOs according to the Beers 2012 and the STOPP/START criteria. The strength of the association between a PIM/PPO and a medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios with 95% confidence intervals (Cl95). RESULTS PlMs and PPOs detected with the STOPP/START criteria are associated with medication-related hospital admissions [OR 3.47; CI95 1.70-7.09], while for the presence of PIMs according to the Beers 2012 criteria a non-significant trend was visible (ORadj 1.49; CI95 0.90-2.47). CONCLUSION Both the STOPP/START criteria and the Beers 2012 criteria can be used to identify older people at risk for medication-related problems. The choice which set of criteria should be used is more dependent on other factors (e.g. national guidelines, practical considerations) than on the association of each set with ADR-related hospital admission

Medication screening using Beers and STOPP/START criteria for elderly patients: Association between potentially inappropriate medication and medication-related hospital admissions

OBJECTIVE To assess the risk of medication-related hospital admissions associated with inappropriate medication use applying the Beers and the STOPP/START criteria. There are multiple screening methods to detect and reduce potentially inappropriate medication [PIM] and prescribing omissions (PPOs). Whether this will result in less medication-related hospitalisations is unknown. DESIGN A nested case-control study was conducted with a subset of patients of the Hospital Admissions Related to Medication (HARM) study. METHODS Cases were defined as patients ≥65 years with a potentially preventable medication-related hospital admission. For each case one control was selected, matched on age and sex. The primary determinant was defined as the presence of one or more PlMs and/or PPOs according to the Beers 2012 and the STOPP/START criteria. The strength of the association between a PIM/PPO and a medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios with 95% confidence intervals (Cl95). RESULTS PlMs and PPOs detected with the STOPP/START criteria are associated with medication-related hospital admissions [OR 3.47; CI95 1.70-7.09], while for the presence of PIMs according to the Beers 2012 criteria a non-significant trend was visible (ORadj 1.49; CI95 0.90-2.47). CONCLUSION Both the STOPP/START criteria and the Beers 2012 criteria can be used to identify older people at risk for medication-related problems. The choice which set of criteria should be used is more dependent on other factors (e.g. national guidelines, practical considerations) than on the association of each set with ADR-related hospital admission

Risk of Postoperative Venous Thromboembolism Among Pregnant Women

Venous thromboembolism (VTE) is a critical complication after surgery. Although pregnancy is a known risk factor of VTE, available data on the risk of postoperative VTE are scarce. Using the American College of Surgeons National Surgical Quality Improvement Program database between 2006 and 2012, we matched 2,582 pregnant women to 103,640 nonpregnant women based on age, race, body mass index, and modified Rogers score. Pregnant women, compared with matched nonpregnant women, experienced higher incidence of VTE (0.5% vs 0.3%; odds ratio 1.93, 95% confidence interval 1.1 to 3.37, p&nbsp;=&nbsp;0.02). Pregnant women also showed higher risk of pneumonia, ventilator dependence ≥48&nbsp;hours, bleeding, and sepsis than did the counterparts. In conclusion, pregnancy was associated with higher risk of VTE after surgery as well as other postoperative complications. The absolute risk difference was small, and careful evaluation against the potential risk and benefit should be given when surgical treatment is considered among pregnant women