Are the recommended allowances for dietary antioxidants adequate?

Recommended dietary allowances are standards for maintaining health. Claims that intakes substantially above the allowances may provide protection from xenobiotics and prevent diseases, including cancer, are examined critically for five nutrients that have antioxidant potential. Major criticism is directed at the failure of epidemiologists to recognize that for many of these nutrients, metabolic differences among individuals preclude a direct relationship between dietary intake and plasma or tissue concentration. Also, the fact that no differences in disease incidence have been described within various species of animals that have markedly different metabolic patterns for some of these nutrients has not been considered. It is concluded that the experimental and epidemiological evidence to data that increased intakes of certain nutrients will have beneficial effects on human health are tenuous.     

Hematologic and oncologic complications in the critically ill child

Admission of a patient to an intensive care unit for management of direct consequences of a hematologic or oncologic disease is occasionally necessary. Such problems included exchange transfusion, sepsis, compression of vital structures by malignant tumor, metabolic derangements, leukostasis, post-operative care, major sickling episodes in vital organs, and disseminated coagulopathy. More often, however, hematologic complications arise in the child critically ill from other causes, such as trauma or infections. The first two sections of this review address blood transfusion and hemostasis, topics likely to have wide application in the care of critically ill children. The last portion discusses problems unique to patients with sickling or malignant disease.     

Assessment of body cell mass at bedside in critically ill patients

Critical illness affects body composition profoundly, especially body cell mass (BCM). BCM loss reflects lean tissue wasting and could be a nutritional marker in critically ill patients. However, BCM assessment with usual isotopic or tracer methods is impractical in intensive care units (ICUs). We aimed to modelize the BCM of critically ill patients using variables available at bedside. Fat-free mass (FFM), bone mineral (Mo), and extracellular water (ECW) of 49 critically ill patients were measured prospectively by dual-energy X-ray absorptiometry and multifrequency bioimpedance. BCM was estimated according to the four-compartment cellular level: BCM = FFM - (ECW/0.98) - (0.73 × Mo). Variables that might influence the BCM were assessed, and multivariable analysis using fractional polynomials was conducted to determine the relations between BCM and these data. Bootstrap resampling was then used to estimate the most stable model predicting BCM. BCM was 22.7 ± 5.4 kg. The most frequent model included height (cm), leg circumference (cm), weight shift (Δ) between ICU admission and body composition assessment (kg), and trunk length (cm) as a linear function: BCM (kg) = 0.266 × height + 0.287 × leg circumference + 0.305 × Δweight - 0.406 × trunk length - 13.52. The fraction of variance explained by this model (adjusted r(2)) was 46%. Including bioelectrical impedance analysis variables in the model did not improve BCM prediction. In summary, our results suggest that BCM can be estimated at bedside, with an error lower than ±20% in 90% subjects, on the basis of static (height, trunk length), less stable (leg circumference), and dynamic biometric variables (Δweight) for critically ill patients.     

Enteral nutrition and hepatosplanchnic region in critically ill patients - friends or foes?

Enteral nutrition (EN) is a preferred way of feeding in critically ill patients unless obvious contraindications such as ileus or active gastrointestinal bleeding are present. Early enteral nutrition as compared to delayed EN or total parenteral nutrition decreases morbidity in postsurgical and trauma patients. The hepatosplanchnic region plays a pivotal role in the pathophysiology of sepsis and multiple organ dysfunction syndrome. The beneficial effects of EN on splanchnic perfusion and energy metabolism have been documented both in healthy volunteers and animal models of sepsis, hemorrhagic shock and burns. By contrast, EN may increase splanchnic metabolic demands, which in turn may lead to oxygen and/or energy demand/supply mismatch, especially when hyperemic response to EN is not preserved. Therefore, the timing of initiation and the dose of EN in patients with circulatory failure requiring vasoactive drugs are a matter of controversy. Interestingly, the results of recent clinical studies suggest that early enteral nutrition may not be harmful even in patients with circulatory compromise. Nevertheless, possible onset of serious complications, the non-occlusive bowel necrosis in particular, have to be kept in mind. Unfortunately, there is only a limited number of clinically applicable monitoring tools for the effects of enteral nutrition in critically ill patients.     

Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans

Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder. Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis. If lymphocyte apoptosis is an important mechanism, specific subsets of lymphocytes may be more vulnerable. A prospective study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma. Spleens from 16 critically ill nonseptic (3 prospective and 13 retrospective) patients were also evaluated. Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis. Interestingly, sepsis did not decrease CD8 T or NK cells. Although there was no overall effect on lymphocytes from critically ill nonseptic patients (considered as a group), certain individual patients did exhibit significant loss of B and CD4 T cells. The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection, a state in which massive lymphocyte clonal expansion should exist. Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells. Similar loss of lymphocytes may be occurring in critically ill patients with other disorders.     

Influence of an aggressive early enteral nutrition protocol on nitrogen balance in critically ill children

The objective was to determine stress related factors and nutritional indices affecting the nitrogen balance (NB) and the creatinine height index (CHI) in critically ill children on early enteral nutrition (EEN). Seventy-one consecutively enrolled critically ill children aged 2 to 204 months, requiring prolonged mechanical ventilation, were studied. All patients were on early intragastric nutrition (Nutrison Pediatric or Standard) from day 1 (energy intake equal to 1/2, 1, 5/4, 6/4 and 6/4 of the predicted basal metabolic rate on days 1-5, respectively). Nitrogen balance and CHI changes determined efficacy. Study patients had severe depletion of somatic protein status on stress day 1 (CHI <60%) but they reached the normal range of somatic protein status at the end of the EEN, on post-stress day 5 (CHI >80%, p <.004). On day 1, none of the patients had positive NB but after 5 days of EEN, 44 (62%) had positive NB and only 27 (38%) had negative NB (p <.0001). Multivariate stepwise regression analysis showed that only the difference of daily given-recommended dietary allowances protein and the total repleted energy were positively correlated (r(2) =.47, p <.001 and r(2) = 34, p =.003, respectively) and multiple organ system failure negatively correlated with the NB (r(2) = -.24, p <.03) on the 5th day of the EEN protocol. Our data suggest that achievement of positive protein and energy balance in relation to the basic metabolic rate using an aggressive EEN protocol improves NB during the acute phase of stress in 2/3 of critically ill children.     

Microdialysis for metabolic monitoring during septicemia]

Currently, metabolic changes in ICU patients in critical states are determined mainly by indirect laboratory parameters (e.g. blood lactate). Microdialysis is a new means of performing metabolic monitoring that permits organ-specific objectification on the basis of interstitial fluid samples. Continuous endotoxin infusion was administered to 10 female pigs and, in addition to hemodynamic monitoring, lactate and glycerol in the subcutaneous, intramuscular and hepatic tissue were measured by microdialysis. The interstitial concentrations of lactate and glycerol rose significantly under endotoxaemia and showed an earlier increase than blood lactate levels. Microdialysis is simple to apply, appears to be a suitable means of obtaining important information about cellular metabolic changes in different tissues of the critically ill patient, and can detect subtle changes that laboratory parameters can identify only later and incompletely.     

Lipid emulsions for parenteral nutrition in critical illness

Critical illness is a life-threatening multisystem process that can result in significant morbidity and mortality. In most patients, critical illness is preceded by a physiological deterioration, characterized by a catabolic state and intense metabolic changes, resulting in malnutrition and impaired immune functions. In this context, parenteral lipid emulsions may modulate inflammatory and immune reactions, depending on their fatty acid composition. These effects appear to be based on complex modifications in the composition and structure of cell membranes, through eicosanoid and cytokine synthesis and by modulation of gene expression. The pathophysiological mechanisms underlying these fatty acid-induced immune function alterations in critical ill patients are however complex and partially understood. Indeed, despite a very abundant literature, experimental and clinical data remain contradictory. The optimization of lipid emulsion composition thus represents a major challenge for clinical medicine, to adequately modulate the inflammatory pathways. In the present review, we first address the metabolic response to aggression, the effects of parenteral lipid emulsions on inflammation and immunity, and finally the controversial place of these lipid emulsions during critical illness. The analysis furthermore highlights the pathophysiological mechanisms underlying the differential effects of lipid emulsions and their potential for improving the handling of critically ill patients.     

危重症患者预后的危险因素及相关指标的预后预测价值分析

目的:探讨危重症患者预后的危险因素,并分析相关指标对患者预后的预测价值。方法:对2016年4月至2018年4月上海交通大学附属第六人民医院救治的5585例ICU危重症患者病例进行回顾性分析,收集患者一般资料、初始乳酸水平、24 h乳酸水平、24 h乳酸清除率以及APACHEII评分等,采用多因素logistic回归分析危重症患者预后的影响因素,ROC曲线评估多项指标预测患者预后的价值。结果:共纳入1465例危重症患者,多因素logistic回归分析显示,住ICU平均时间长、APACHEII评分高、初始乳酸水平大于4 mmol/L、24 h乳酸清除率低、术后肾功能异常是危重症患者住院期间死亡的危险因素(P0.05),24 h乳酸清除率、APACHEII评分及初始乳酸水平三者联合评估预测患者住院死亡率的ROC曲线下面积(ROC-AUC)为0.900,高于单独检测。结论:住ICU时间、APACHEII评分、初始乳酸水平、24 h乳酸清除率、术后肾功能是危重症患者住院期间死亡的影响因素,初始乳酸水平、24 h乳酸清除率和APACHEII评分联合使用可以更好地预测危重症患者的短期预后。     

Parallel Exploitation of Diverse Host Nutrients Enhances Salmonella Virulence

Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics, competitive infections, and computational approaches to obtain a comprehensive overview of Salmonella nutrition and growth in a mouse typhoid fever model. The data revealed that Salmonella accessed an unexpectedly diverse set of at least 31 different host nutrients in infected tissues but the individual nutrients were available in only scarce amounts. Salmonella adapted to this situation by expressing versatile catabolic pathways to simultaneously exploit multiple host nutrients. A genome-scale computational model of Salmonella in vivo metabolism based on these data was fully consistent with independent large-scale experimental data on Salmonella enzyme quantities, and correctly predicted 92% of 738 reported experimental mutant virulence phenotypes, suggesting that our analysis provided a comprehensive overview of host nutrient supply, Salmonella metabolism, and Salmonella growth during infection. Comparison of metabolic networks of other pathogens suggested that complex host/pathogen nutritional interfaces are a common feature underlying many infectious diseases.     

Hemodynamic monitoring: catheter insertion techniques,complications and trouble-shooting.

Hemodynamic monitoring is an important aspect of contemporary intensive care of the critically ill patient. The potential problems associated with invasive monitoring fall into two general categories: those related to technical pitfalls and those related to patient complications. An awareness of these problems combined with technical expertise and an understanding of cardiovascular physiology can minimize complications and make hemodynamic monitoring a safe and useful procedure.     

Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed

     

Particularidades clínicas del paciente crítico con infección fúngica invasora

BackgroundInvasive fungal infection (IFI) is an entity that encompasses different types of infections caused by different types of those fungi pathogenic for humans. In the setting of critically ill patients with multiple and oftenconcurrent risk factors and comorbidities the most common are those caused by the Candida and Aspergillus species. Among the characteristics of IFI in critically ill patients, three aspects can be highlighted: those related to the host (e.g.: risk factors, clinical severity), those related with the pathogen (sensitivity, virulence), or those concerning antifungal treatment (spectrum, features PK / PD, safety, interactions). The fungus that most often causes an IFI in critically ill patients is Candida; the most common type infections are candidemia, Candida peritonitis and catheter-related infections. In recent years new antifungal treatments have expanded the therapeutic options, with echinocandins as a clear choice, often the first in the latest guidelines in critically ill patients with IFI.Case reportWe report the case of a critically ill patient having the most common risk factors, multiple organ dysfunction and development of an IFI. The complexity of establishing an antifungal treatment from the moment of its inception, its setting, and the considerations of the different therapeutic possibilities according to organ dysfunction of the patient are discussed. The antifungal treatment options mentioned in the current guidelines and recommendations are also evaluated.ConclusionsThe most common fungal infection in critically ill patients is invasive candidiasis, with candidemia or candida peritonitis being the most frequent clinical presentations. Candins have brought new possibilities for treating these complex patients due to their good safety profile and clinical efficacy.     

Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes

PURPOSE OF REVIEW: This review summarizes the evidence for benefits of magnesium on metabolic abnormalities, inflammatory parameters, and cardiovascular risk factors and related-potential mechanisms. Controversy due to contrasting results in the literature is also discussed. RECENT FINDINGS: Increased dietary magnesium intake confers protection against the incidence of diabetes, metabolic syndrome, hypertension, and cardiovascular disease. It ameliorates insulin resistance, serum lipid profiles, and lowers inflammation, endothelial dysfunction, oxidative stress, and platelet aggregability. Magnesium acts as a mild calcium antagonist on vascular smooth muscle tone, and on postreceptor insulin signaling; it is critically involved in energy metabolism, fatty acid synthesis, glucose utilization, ATPase functions, release of neurotransmitters, and endothelial cell function and secretion. Prospective studies, however, have found only a modest effect for dietary magnesium on incident pathologies. Furthermore, magnesium supplementation on glucose metabolism, blood lipid levels, and ischemic heart disease has given inconsistent results. SUMMARY: There is strong biological plausibility for the direct impact of magnesium intake on metabolic and cardiovascular risk factors, but in-vivo magnesium deficiency might play only a modest role. Reverse causality, the strong association between magnesium and other beneficial nutrients, or the possibility that people who choose magnesium-rich foods are more health-conscious may be confounding factors.     

An Anthelmintic Drug,Pyrvinium Pamoate,Thwarts Fibrosis and Ameliorates Myocardial Contractile Dysfunction in a Mouse Model of Myocardial Infarction

Metabolic adaptation to limited supplies of oxygen and nutrients plays a pivotal role in health and disease. Heart attack results from insufficient delivery of oxygen and nutrients to the heart, where cardiomyocytes die and cardiac fibroblasts proliferate – the latter causing scar formation, which impedes regeneration and impairs contractility of the heart. We postulated that cardiac fibroblasts survive metabolic stress by adapting their intracellular metabolism to low oxygen and nutrients, and impeding this metabolic adaptation would thwart their survival and facilitate the repair of scarred heart. Herein, we show that an anthelmintic drug, Pyrvinium pamoate, which has been previously shown to compromise cancer cell survival under glucose starvation condition, also disables cardiac fibroblast survival specifically under glucose deficient condition. Furthermore, Pyrvinium pamoate reduces scar formation and improves cardiac contractility in a mouse model of myocardial infarction. As Pyrvinium pamoate is an FDA-approved drug, our results suggest a therapeutic use of this or other related drugs to repair scarred heart and possibly other organs.     

Apicomplexan mitochondrial metabolism: a story of gains, losses and retentions

Apicomplexans form a large group of obligate intracellular parasites that occupy diverse environmental niches. To adapt to their hosts, these parasites have evolved sophisticated strategies to access host-cell nutrients and minimize exposure to the host's defence mechanisms. Concomitantly, they have drastically reshaped their own metabolic functions by retaining, losing or gaining genes for metabolic enzymes. Although several Apicomplexans remain experimentally intractable, bioinformatic analyses of their genomes have generated preliminary metabolic maps. Here, we compare the metabolic pathways of five Apicomplexans, focusing on their different mitochondrial functions, which highlight their adaptation to their individual intracellular habitats.     

Quantitative aspects of metabolic organization: a discussion of concepts

Metabolic organization of individual organisms follows simple quantitative rules that can be understood from basic physical chemical principles. Dynamic energy budget (DEB) theory identifies these rules, which quantify how individuals acquire and use energy and nutrients. The theory provides constraints on the metabolic organization of subcellular processes. Together with rules for interaction between individuals, it also provides a basis to understand population and ecosystem dynamics. The theory, therefore, links various levels of biological organization. It applies to all species of organisms and offers explanations for body-size scaling relationships of natural history parameters that are otherwise difficult to understand. A considerable number of popular empirical models turn out to be special cases of the DEB model, or very close numerical approximations. Strong and weak homeostasis and the partitionability of reserve kinetics are cornerstones of the theory and essential for understanding the evolution of metabolic organization.     

Recommendations for preventing transmission of HIV in health care settings.

The initial resuscitation and stabilization provided to a critically ill or injured child is often an important determinant of outcome. Before transfer to a tertiary care facility the initial care may be provided by physicians unaccustomed to managing critically ill children. The authors outline the unique aspects of resuscitation and stabilization of the critically ill child and give guidelines for the initial management of diseases affecting the central nervous system and respiratory tract (the most frequent indications for transfer to a tertiary care facility) and other, less frequent but important problems. In many situations it is worth while to enlist the expertise of the tertiary care centre, either by telephone consultation or by dispatch of a specially trained transport team.