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Biomedical subjects

R Chioléro

Publications and source records attributed to R Chioléro.

At least 19 recordsLinked to original sources

Impaired insulin response after oral but not intravenous glucose in heart- and liver-transplant recipients.

BACKGROUND: The prevalence of diabetes is high after transplantation. We hypothesized that liver transplantation induces additional alterations of glucose homeostasis because of liver denervation. METHODS: Nondiabetic patients with a heart (n=9) or liver (n=9) transplant and healthy subjects (n=8) were assessed using a two-step hyperglycemic clamp (7.5 and 10 mmol/L). Thereafter, an oral glucose load (0.65 g/kg fat free mass) was administered while glucose was clamped at 10 mmol/L. Glucose appearance from the gut was calculated as the difference between glucose appearance (6,6 2H2 glucose) and exogenous glucose infusion. Plasma insulin, glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide(GIP) concentrations were compared after intravenous and oral glucose. RESULTS: After oral glucose, the glucose appearance from the gut was increased 52% and 81% in liver- and heart-transplant recipients (P<0.05). First-pass splanchnic glucose uptake was reduced by 39% in liver-transplant and 64% in heart-transplant patients (P<0.05). After oral but not intravenous glucose, there was an impairment of insulin secretion in both transplant groups relative to the controls. Plasma concentrations of GIP and GLP-1 increased similarly in all three groups after oral glucose. CONCLUSIONS: First-pass hepatic glucose extraction is decreased after heart and liver transplant. Insulin secretion elicited by oral, but not intravenous glucose, is significantly reduced in both groups of patients. There was no difference between liver- and heart-transplant recipients, indicating that hepatic denervation was not involved. These data suggest an impairment in the beta-cell response to neural factors or incretin hormones secondary to immunosuppressive treatment.

Administration, Oral↗

Fish oil prevents the adrenal activation elicited by mental stress in healthy men.

OBJECTIVES: A diet rich in n-3 fatty acids (fish oils) is associated with reduced risks of cardiovascular and metabolic diseases, but the mechanisms remain incompletely understood. Sympathoadrenal activation is postulated to be involved in the pathogenesis of these diseases, and may be inhibited by n-3 fatty acids. We therefore evaluated the effects of a diet supplemented with n-3 fatty acids on the stimulation of the sympathetic nervous system and of stress hormones elicited by a mental stress. METHODS: Seven human volunteers were studied on two occasions, before and after 3 weeks of supplementation with 7.2 g/day fish oil. On each occasion, the concentrations of plasma cortisol, and catecholamines, energy expenditure (indirect calorimetry), and adipose tissue lipolysis (plasma non esterified fatty acid concentrations) were monitored in basal conditions followed by a 30 min mental stress (mental arithmetics and Stroop's test) and a 30 min recovery period. RESULTS: In control conditions, mental stress significantly increased heart rate, mean blood pressure, and energy expenditure. It increased plasma epinephrine from 60.9 +/- 6.2 to 89.3 +/- 16.1 pg/ml (p<0.05), plasma cortisol from 291 +/- 32 to 372 +/- 37 micromol/l (p<0.05) and plasma non esterified fatty acids from 409 +/- 113 to 544 +/- 89 micromol/l (p<0.05). After 3 weeks of a diet supplemented with n-3 fatty acids, the stimulation by mental stress of plasma epinephrine, cortisol, energy expenditure, and plasma non esterified fatty acids concentrations, were all significantly blunted. CONCLUSION: Supplementation with n-3 fatty acids inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system.

Adult↗

[The heart transplant in Lausanne from 1987 to 2003].

Since the availability of ciclosporine, the survival after heart transplantation has dramatically improved. We present our results since the beginning of our experience in 1987. We treated in the Lausanne University hospital, 150 patients for end-stage cardiac disease. Hundred and fifty-two transplantations were performed. The survival rate is comparable to the literature with 81% at one year, 70% at five year and 63 at ten year included the hospital mortality. We review the incidence of complications during the follow-up and report the modification in the management of these patients especially concerning the immunosuppression.

Adult↗

CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia.

OBJECTIVES: In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection. MEASUREMENTS: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay. RESULTS: The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock.

Antigens, CD↗

Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.

HYPOTHESIS: Liver transplantation results in hepatic denervation. This may produce alterations of liver energy and substrate metabolism, which may contribute to weight gain after liver transplantation. DESIGN: Prospective clinical study. SETTING: Liver transplantation clinics in a university hospital. PATIENTS: Seven nondiabetic patients with cirrhosis were recruited while on a waiting list for liver transplantation. Seven healthy subjects were recruited as controls. INTERVENTION: Orthotopic liver transplantation. MAIN OUTCOME MEASURES: Evaluation of energy and substrate metabolism after ingestion of a glucose load with indirect calorimetry was performed before, 2 to 6 weeks after, and 5 to 19 months after transplantation. Whole-body glucose oxidation and storage and glucose-induced thermogenesis were calculated. RESULTS: Patients with cirrhosis had modestly elevated resting energy expenditure and normal glucose-induced thermogenesis and postprandial glucose oxidation and storage. These measures remained unchanged after liver transplantation despite a significant increase in postprandial glycemia. Patients, however, gained an average of 3 kg of body weight after 5 to 19 months compared with their weight before transplantation. CONCLUSION: Liver denervation secondary to transplantation does not lead to alterations of energy metabolism after ingestion of a glucose load.

Blood Glucose↗

Human errors in a multidisciplinary intensive care unit: a 1-year prospective study.

OBJECTIVES: To determine the incidence and identify risk factors of critical incidents in an ICU. DESIGN: Prospective observational study of consecutive patients admitted over 1 year to an ICU. Critical incidents were recorded using predefined criteria. Their causes and consequences were analysed. The causes were classified as technical failure, patient's underlying disease, or human errors (subclassified as planning, execution, or surveillance). The consequences were classified as lethal, leading to sequelae, prolonging the ICU stay, minor, or without consequences. The correlation between critical incidents and specific factors including patient's diagnosis and severity score, use of monitoring and therapeutic modalities was analysed by uni- and multivariate analysis. SETTING: An 11-bed multidisciplinary ICU in a non-university teaching hospital. PATIENTS: 1,024 consecutive patients admitted to the ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The median length of ICU stay by the 1,024 patients was 1.9 days. Of the 777 critical incidents reported 2% were due to technical failure and 67 % to secondary to underlying disease. There were 241 human errors (31%) in 161 patients, evenly distributed among planning (n = 75), execution (n = 88), and surveillance (n = 78). One error was lethal, two led to sequelae, 26 % prolonged ICU stay, and 57 % were minor and 16 % without consequence. Errors with significant consequences were related mainly to planning. Human errors prolonged ICU stay by 425 patient-days, amounting to 15 % of ICU time. Readmitted patients had more frequent and more severe critical incidents than primarily admitted patients. CONCLUSIONS: Critical incidents add morbidity, workload, and financial burden. A substantial proportion of them are related to human factors with dire consequences. Efforts must focus on timely, appropriate care to avoid planning and execution mishaps at the beginning of the ICU stay; surveillance intensity must be maintained, specially after the fourth day.

Adolescent↗

Early metabolic and splanchnic responses to enteral nutrition in postoperative cardiac surgery patients with circulatory compromise.

OBJECTIVES: To assess the hemodynamic and metabolic adaptations to enteral nutrition (EN) in patients with hemodynamic compromise. DESIGN AND SETTING: Prospective study in a university hospital surgical ICU, comparing baseline (fasted) with continuous EN condition. PATIENTS: Nine patients requiring hemodynamic support by catecholamines (dobutamine and/or norepinephrine) 1 day after cardiac surgery under cardiopulmonary bypass. INTERVENTION: Isoenergetic EN via a postpyloric tube while catecholamine treatment remained constant. Baseline (fasted) condition was compared to continuous EN condition. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI), mean arterial pressure (MAP), pulmonary and wedge pressures, indocyanine green (ICG) clearance, gastric tonometry, plasma glucose and insulin, and glucose turnover (6,62H2-glucose infusion) were determined repetitively every 60 min during 2 h of baseline fasting condition and 3 h of EN. During EN CI increased (from 2.9 +/- 0.5 to 3.3 +/- 0.5 l min-1 m-2), MAP decreased transiently (from 78 +/- 7 to 70 +/- 11 mmHg), ICG clearance increased (from 527 +/- 396 to 690 +/- 548 ml/min), and gastric tonometry remained unchanged, while there were increases in glucose (158 +/- 23 to 216 +/- 62 mg/dl), insulin (29 +/- 23 to 181 +/- 200 mU/l), and glucose rate of appearance (2.4 +/- 0.2 to 3.3 +/- 0.2 mg min-1 kg-1). CONCLUSIONS: The introduction of EN in these postoperative patients increased CI and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early EN may be adequate after cardiac surgery even in patients requiring inotropes.

Adaptation, Physiological↗

Adaptive support ventilation for fast tracheal extubation after cardiac surgery: a randomized controlled study.

BACKGROUND: Adaptive support ventilation (ASV) is a microprocessor-controlled mode of mechanical ventilation that maintains a predefined minute ventilation with an optimal breathing pattern (tidal volume and rate) by automatically adapting inspiratory pressure and ventilator rate to changes in the patient's condition. The aim of the current study was to test the hypothesis that a protocol of respiratory weaning based on ASV could reduce the duration of tracheal intubation after uncomplicated cardiac surgery ("fast-track" surgery). METHODS: A group of patients being given ASV (group ASV) was compared with a control group (group control) in a randomized controlled study. After coronary artery bypass grafting during general anesthesia with midazolam and fentanyl, patients were randomly assigned to group ASV or group control. Both protocols were divided into three predefined phases, and weaning progressed according to arterial blood gas and clinical criteria. In phase 1, ASV mode was set at 100% of the theoretical value of volume/minute in group ASV, and synchronized intermittent mandatory ventilation mode was used in group control. When spontaneous breathing occurred, ASV setting was reduced by 50% of minute ventilation (phase 2) and again by 50% (phase 3), and the trachea was extubated. In group control, the ventilator was switched to 10 cm H2O inspiratory pressure support (phase 2), then to 5 cm H2O (phase 3) until extubation. RESULTS: Forty-nine patients were enrolled. Sixteen patients completed the ASV protocol, and 20 the standard protocol; 7 patients were excluded in group ASV and 6 in group control according to explicit, predefined criteria. There were no differences between groups in perioperative characteristics or in the doses of sedation. The primary outcome of the study, that is, the duration of tracheal intubation, was shorter in group ASV than in group control (median [quartiles]: 3.2 [2.5-4.6] vs. 4.1 [3.1-8.6] h; P < 0.02). Fewer arterial blood analyses were performed in group ASV (median number [quartiles]: 3 [3-4] vs. 4 [3-6]), suggesting that fewer changes in the settings of the ventilator were required in this group. CONCLUSIONS: A respiratory weaning protocol based on ASV is practicable; it may accelerate tracheal extubation and simplify ventilatory management in fast-track patients after cardiac surgery. The evaluation of potential advantages of the use of such technology on patient outcome and resource utilization deserves further studies.

Aged↗

Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle.

Hyperinsulinemia increases lactate release by various organs and tissues. Whereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle Na+-K+-ATPase is responsible for increased muscle lactate production. To test this hypothesis, we assessed muscle lactate release in healthy volunteers from the [13C]lactate concentration in the effluent dialysates of microdialysis probes inserted into the tibialis anterior muscles on both sides and infused with solutions containing 5 mmol/l [U-13C]glucose. On one side, the microdialysis probe was intermittently infused with the same solution additioned with 2.10(-5) M ouabain. In the basal state, [13C]lactate concentration in the dialysate was not affected by ouabain. During a euglycemic-hyperinsulinemic clamp, [13C]lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely reversed by ouabain (56% inhibition compared with values in the dialysate collected from the contralateral probe). These data indicate that insulin stimulates muscle lactate release by activating Na+-K+-ATPase in healthy humans.

Adult↗

[Twelve years of liver transplantation in Lausanne].

From 1988 to June 2000 138 transplantations were performed in 129 adult patients. Actuarial patient and graft survivals have been 80.7% and 75.4% at one year and 67.8% and 63.5% at 10 years. This compares favourably with the statistics of the European Liver Transplant Registry that collected data from more than 30,000 grafts. Over the twelve years of activity, the indications have become more liberal and the techniques have been simplified. The waiting list has therefore grown and some patients are now unfortunately dying before a graft can be found because the number of brain dead donors remains stable. In order to palliate this shortage, older donors are now being accepted even with co-morbidities and/or moderate alterations of the liver function tests. The use of live donors and the split of the best cadaveric grafts for two recipients will also reduce the gap between the demand and the offer.

Actuarial Analysis↗

Effect of liver transplantation on hepatic glucose metabolism in a patient with type I glycogen storage disease.

BACKGROUND: In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis. METHODS: Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects. RESULTS: Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient. CONCLUSIONS: Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Adolescent↗

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Adult↗

Pain pattern and left internal mammary artery grafting.

BACKGROUND: This study was designed to determine whether the pain pattern in patients with an internal mammary artery (IMA) harvest differs from that in other cardiac operations and whether these patients present specific characteristics with clinical implications. METHODS: One hundred patients with left IMA grafting (IMA group) were compared prospectively with 100 patients who had a heart operation without IMA harvest (non-IMA group). Pain assessment was performed on postoperative days (POD) 1, 2, 3, and 7, and included pain intensity (10-point scale) and pain localization. RESULTS: In the IMA group, pain intensity was higher on POD 2 (4.2 +/- 2.4 versus 3.2 +/- 2.3, p < 0.01), and there were more patients without pain on POD 7 (32 versus 19, p = 0.03). In the IMA group, more patients had left basal thoracic pain throughout the entire study period and had sternal pain on POD 7, whereas more patients in the non-IMA group complained about back pain during the early postoperative period. CONCLUSIONS: The impact of IMA harvest on pain intensity is moderate, but the pain localization pattern of each group exhibits specific features that could help to better target pain management.

Adult↗

Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients.

BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.

Adult↗

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

APACHE↗

Segmental bioelectrical impedance analysis to assess perioperative fluid changes.

OBJECTIVES: Perioperative fluid accumulation determination is a challenge for the clinician. Bioelectrical impedance analysis (BIA) is a noninvasive method based on the electrical properties of tissues, which can assess body fluid compartments. The study aimed at assessing their changes in three types of surgery (thoracic, abdominal, and intracranial) requiring various regimens of fluid administration. DESIGN: Prospective descriptive trial. PATIENTS: A total of 26 patients scheduled for elective surgery were separated into three groups according to site of surgery: thoracic (n = 8), abdominal aortic (n = 8), and brain surgery (n = 10). SETTING: University teaching hospital. INTERVENTION: None. MEASUREMENTS: Whole body, segmental (arm, trunk, and legs) BIA at multiple frequency (0.5, 50, 100 kHz) was used to assess perioperative fluid accumulation after surgery. The fluid balances were calculated from the charts. RESULTS: The patients were aged 62+/-4 yrs. Fluid balances were 4.8+/-1.0 L, 4.1+/-0.5 L, and 1.9+/-0.3 L, respectively, in the three groups. In trunk surgery patients, fluid accumulation was detected as a drop in impedance in the operated area at all frequencies. In the operated area, there was an expansion of both intra- and extracellular compartments. A reduction in high frequencies' impedance in the legs was only detected after aortic surgery. Fluid accumulation and trunk impedance changes were strongly correlated. Neurosurgery only induced minor body fluid changes. CONCLUSIONS: Segmental BIA is able to detect and localize perioperative fluid accumulation. It may become a bedside tool to quantify and to localize fluid accumulation.

Abdomen↗

Major reduction in plasma Lp(a) levels during sepsis and burns.

Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5- to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels.

Adult↗