New nonculture-based methods for the diagnosis of invasive candidiasis.

PURPOSE OF REVIEW: Invasive candidiasis is a severe infectious complication occurring mostly in onco-hematologic and surgical patients. Its conventional diagnosis is insensitive and often late, leading to a delayed treatment and a high mortality. The purpose of this article is to review recent contributions in the nonconventional diagnostic approaches of invasive candidiasis, both for the detection of the epidose and the characterization of the etiologic agent. RECENT FINDINGS: Antigen-based tests to detect invasive candidiasis comprise a specific test, mannan, as well as a nonspecific test, beta-D-glucan. Both have a moderate sensitivity and a high specificity, and cannot be recommended alone as a negative screening tool or a positive syndrome driven diagnostic tool. Molecular-based tests still have not reached the stage of rapid, easy to use, standardized tests ideally complementing blood culture at the time of blood sampling. New tests (fluorescence in-situ hybridization or mass spectrometry) significantly reduce the delay of identification of Candida at the species level in positive blood cultures, and should have a positive impact on earlier appropriate antifungal therapy and possibly on outcome. SUMMARY: Both antigen-based and molecular tests appear as promising new tools to complement and accelerate the conventional diagnosis of invasive candidiasis with an expected significant impact on earlier and more focused treatment and on prognosis.

Quality Of Attachment, Perinatal Risk, And Mother-Infant Interaction In A High-Risk Premature Sample

Thirty-three families, each with a premature infant born less than 33 gestational weeks, were observed in a longitudinal exploratory study. Infants were recruited in a neonatal intensive care unit, and follow-up visits took place at 4 months and 12 months of corrected age. The severity of the perinatal problems was evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton, 1991). At 4 months, mother infant play interaction was observed and coded according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters. & S. Wall, 1978) was administered. Results indicate a strong correlation between the severity of perinatal problems and the quality of attachment at 12 months. Based on the PERI, infants with high medical risks more frequently tended to be insecurely attached. There also was a significant correlation between insecure attachment and dyadic play interaction at 4 months (i.e., maternal controlling behavior and infant compulsive compliance). Moreover, specific dyadic interactive patterns could be identified as protective or as risk factors regarding the quality of attachment. Considering that attachment may have long-term influence on child development, these results underline the need for particular attention to risk factors regarding attachment among premature infants.

Das Holprinzip in der Pädiatrie und Neonatologie [The collecting principle in pediatrics and neonatology]

Quality medical care during transport of critically ill pediatric and neonatal patients is only possible if the referring hospital and the regional center cooperate closely. The experience of physicians and nurses involved is of great importance, and the choice of the transporting team should depend on the medical status of the patient and the skills of the physicians and nurses or paramedics. Critically ill children and neonates should be transported by specialized teams. Our statistics from the last 12 years show an increasing number of transports, with the majority of patients being referred from peripheral hospitals.

Is (1→3)-β-D-glucan the missing link from bedside assessment to pre-emptive therapy of invasive candidiasis?

ABSTRACT: Invasive candidiasis is a frequent life-threatening complication in critically ill patients. Early diagnosis followed by prompt treatment aimed at improving outcome by minimizing unnecessary antifungal use remains a major challenge in the ICU setting. Timely patient selection thus plays a key role for clinically efficient and cost-effective management. Approaches combining clinical risk factors and Candida colonization data have improved our ability to identify such patients early. While the negative predictive value of scores and predicting rules is up to 95 to 99%, the positive predictive value is much lower, ranging between 10 and 60%. Accordingly, if a positive score or rule is used to guide the start of antifungal therapy, many patients may be treated unnecessarily. Candida biomarkers display higher positive predictive values; however, they lack sensitivity and are thus not able to identify all cases of invasive candidiasis. The (1→3)-β-D-glucan (BG) assay, a panfungal antigen test, is recommended as a complementary tool for the diagnosis of invasive mycoses in high-risk hemato-oncological patients. Its role in the more heterogeneous ICU population remains to be defined. More efficient clinical selection strategies combined with performant laboratory tools are needed in order to treat the right patients at the right time by keeping costs of screening and therapy as low as possible. The new approach proposed by Posteraro and colleagues in the previous issue of Critical Care meets these requirements. A single positive BG value in medical patients admitted to the ICU with sepsis and expected to stay for more than 5 days preceded the documentation of candidemia by 1 to 3 days with an unprecedented diagnostic accuracy. Applying this one-point fungal screening on a selected subset of ICU patients with an estimated 15 to 20% risk of developing candidemia is an appealing and potentially cost-effective approach. If confirmed by multicenter investigations, and extended to surgical patients at high risk of invasive candidiasis after abdominal surgery, this Bayesian-based risk stratification approach aimed at maximizing clinical efficiency by minimizing health care resource utilization may substantially simplify the management of critically ill patients at risk of invasive candidiasis.

Should Hyperglycemia in Critically Ill Children Be Treated?

Introduction: In adults, strict control of hyperglycemia reduces mortality and morbidity. There is controversy in medical patients and neurological patients who can suffer of neuroglucopenia. Objectives: To determine prevalence and prognostic significance of hyperglycemia among critically ill non-diabetic children. To evaluate which patients will best benefit of insulin treatment. Methods: Retrospective study using blood glucose levels (GLUC: 9015 values, 923 patients) in our PICU from 01.2003 to 12.2005. 11 Patients with DKA were excluded. Overall PICU mortality was 3.7%. Hyperglycemia was defined at 6.1 mmol/L and different cutoff values (6.1, 8.3 and 11.1 mmol/l) were analyzed for glycemia at admission (GLUC). Sustained hyperglycemia was evaluated with the area under the curve normalized per hour (48h-AUC/h) for the first 48 h. The prevalence of hypo (_3mmol/L), hyperglycemia and PICU death were analyzed. Results: Trough the use of different cutoff values (_6.1, _8.3 and _11.1 mmol/l), prevalence of hyperglycemia at admission was 31.8 %, 16.8% and 10.3%; associated mortality was 2.8%, 4.0% and 15.2% respectively, significantly correlated to cutoff values (r_0.95, p_0.05). Prevalence of hypoglycemia at admission was low (0.9% with no death). 48h-AUC(mmol/L/h) was computed in 747 children (30 deaths). Prevalence of hyperglycemic 48h-AUC values was 47.5%, 17.3% and 4.0% with a respective mortality of 3.4%, 6.3% and 20.7% (r_0.97, p_0.03). For those with high GLUC and high 48h-AUC (_ 11.1 mmol/L) mortality was high (31.5%), but it decrease dramatically to 5.5% when 48h-AUC decrease spontaneously to values _8.3 mmol/L/h. Finally, when patients with severe neurological lesions (GCS_3, n_22) where excluded, increased mortality was observed only for GLUC (n_ 86) and 48h-AUC (n_26) higher than 11.1 mmol/L. Conclusions: Hyperglycemia at admission and even more sustained hyperglycemia (AUC) are highly correlated to mortality in PICU. But children who will have benefit of insulin therapy represent only 3% of our population, much lower than for adults.

The effect of thrombolysis on short-term improvement depends on initial stroke severity.

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24 h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24 h after admission was associated with the NIHSS score at admission (β = 1, p < 0.001), initial glucose level (β = 0.05, p < 0.002) and thrombolytic intervention (β = -2.91, p < 0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severity.

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients.

BACKGROUND AND AIMS: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. METHODS: Prospective observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+/-SD, linear regressions between energy balance and outcome variables. RESULTS: Forty eight patients aged 57+/-16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11+/-8 days, ICU stay 15+/-9 was days, and 30-days mortality was 38%. Time to feeding was 3.1+/-2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090+/-930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+/-10,520 kcal, and correlated with complications (P < 0.001), already after 1 week. CONCLUSION: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.

Blood glucose level on postoperative day 1 is predictive of adverse outcomes after cardiovascular surgery.

AIM: Hyperglycaemia is now a recognized predictive factor of morbidity and mortality after coronary artery bypass grafting (CABG). For this reason, we aimed to evaluate the postoperative management of glucose control in patients undergoing cardiovascular surgery, and to assess the impact of glucose levels on in-hospital mortality and morbidity. METHODS: This was a retrospective study investigating the association between postoperative blood glucose and outcomes, including death, post-surgical complications, and length of stay in the intensive care unit (ICU) and in hospital. RESULTS: A total of 642 consecutive patients were enrolled into the study after cardiovascular surgery (CABG, carotid endarterectomy and bypass in the lower limbs). Patients' mean age was 68+/-10 years, and 74% were male. In-hospital mortality was 5% in diabetic patients vs 2% in non-diabetic patients (OR: 1.66, P=0.076). Having blood glucose levels in the upper quartile range (> or =8.8 mmol/L) on postoperative day 1 was independently associated with death (OR: 10.16, P=0.0002), infectious complications (OR: 1.76, P=0.04) and prolonged ICU stay (OR: 3.10, P<0.0001). Patients presenting with three or more hypoglycaemic episodes (<4.1 mmol/L) had increased rates of mortality (OR: 9.08, P<0.0001) and complications (OR: 8.57, P<0.0001). CONCLUSION: Glucose levels greater than 8.8 mmol/L on postoperative day 1 and having three or more hypoglycaemic episodes in the postoperative period were predictive of mortality and morbidity among patients undergoing cardiovascular surgery. This suggests that a multidisciplinary approach may be able to achieve better postoperative blood glucose control.

Management of refractory status epilepticus in adults: still more questions than answers.

Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia.

OBJECTIVE: Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome. METHODS: A prospective cohort of comatose CA patients treated with TH (32-34°C, 24h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT=time from hospital admission to induced BT target <34°C), cooling rate (spontaneous BT-induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined. RESULTS: A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N=90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7-35.9]°C vs. 35.1 [34.4-35.8]°C, p=0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25-363]min vs. 270 [158-375]min, p=0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2-0.5]°C/h vs. 0.3 [0.2-0.4]°C/h, p=0.65). Longer duration of passive rewarming (600 [464-744]min vs. 479 [360-600]min, p<0.001) was associated with mortality. CONCLUSIONS: Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature.

Brain dysfunction in sepsis: what can we learn from cerebral perfusion studies?

Investigations on the relationship between sepsis, brain dysfunction, and cerebral perfusion are methodologically very difficult to perform. It is important to interpret the results of such studies in view of our limited ability to diagnose and quantify brain dysfunction and to consider our limited understanding of the mechanisms that lead to or are associated with brain dysfunction in sepsis.

The epidemiology and antigenic characterization of influenza viruses isolated in Curitiba, South Brazil

Several studies conducted all over the world have reported that the influenza virus is associated with great morbidity and mortality rates. In this study, we analyzed the incidence of the influenza virus between 2000 and 2003 in Curitiba. We studied 1621 samples obtained from outpatients and hospitalized patients of both sexes and all ages. The study was conducted at the local primary care health units (outpatients) and at the tertiary care unit (hospitalized) of the General Hospital of the Federal University in the state of Paraná, Brazil. Nasopharyngeal aspirates and, eventually, bronchoalveolar lavage were assayed for the presence of viral antigens, either by indirect immunofluorescence or cell culture. Of the samples studied, 135 (8.3%) were positive for influenza virus, and of those, 103 (76.3%) were positive for type A and 32 (23.7%) for type B. Additionally, positive samples were analyzed by reverse transcription followed by polymerase chain reaction and subtypes H1 and H3 were identified from this group. A high incidence of positive samples was observed mainly in the months with lower temperatures. Furthermore, outpatients showed a higher incidence of influenza viruses than hospitalized patients.