Strategies for the successful implementation of viral laboratory automation.

It has been estimated that more than 70% of all medical activity is directly related to information providing analytical data. Substantial technological advances have taken place recently, which have allowed a previously unimagined number of analytical samples to be processed while offering high quality results. Concurrently, yet more new diagnostic determinations have been introduced - all of which has led to a significant increase in the prescription of analytical parameters. This increased workload has placed great pressure on the laboratory with respect to health costs. The present manager of the Clinical Laboratory (CL) has had to examine cost control as well as rationing - meaning that the CL's focus has not been strictly metrological, as if it were purely a system producing results, but instead has had to concentrate on its efficiency and efficacy. By applying re-engineering criteria, an emphasis has had to be placed on improved organisation and operating practice within the CL, focussing on the current criteria of the Integrated Management Areas where the technical and human resources are brought together. This re-engineering has been based on the concepts of consolidating and integrating the analytical platforms, while differentiating the production areas (CORE Laboratory) from the information areas. With these present concepts in mind, automation and virological treatment, along with serology in general, follow the same criteria as the rest of the operating methodology in the Clinical Laboratory.

Lactate quartile concentration and prognosis in severe sepsis and septic shock.

Introduct ion The Surviving Sepsis Campaign (SSC) indicates that a lactate (LT) concentration greater than 4ımmol/l indicates early resuscitation bundles. However, several recent studies have suggested that LT values lower than 4ımmol/l may be a prognostic marker of adverse outcome. The aim of this study was to identify clinical and analytical prognostic parameters in severe sepsis (SS) or septic shock (ShS) according to quartiles of blood LT concentration. Methods A cohort study was designed in a polyvalent ICU. We studied demographic, clinical and analytical parameters in 148 critically ill adults, within 24ıhours from SS or ShS onset according to SSC criteria. We tested for diı erences in baseline characteristics by lactate interval using a KruskalıWallis test for continuous data or a chi-square test for categorical data and reported the median and interquartile ranges; SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). Results We analyzed 148 consecutive episodes of SS (16%) or ShS (84%). The median age was 64 (interquartile range, 48.7 to 71)ıyears; male: 60%. The main sources of infection were respiratory tract 38% and intra-abdomen 45%; 70.7% had medical pathology. Mortality at 28ıdays was 22.7%. Quartiles of blood LT concentration were quartile 1 (Q1): 1.87ımmol/l or less, quartile 2 (Q2): 1.88 to 2.69ımmol/l, quartile 3 (Q3): 2.7 to 4.06ımmol/l, and quartile 4 (Q4): 4.07ımmol/l or greater (Tableı1). The median LT concentrations of each quartile were 1.43 (Q1), 2.2 (Q2), 3.34 (Q3), and 5.1 (Q4) mmol/l (Pı<0.001). The diı erences between these quartiles were that the patients in Q1 had signiı cantly lower APACHE II scores (Pı=ı0.04), SOFA score (Pı=ı0.024), number of organ failures (NOF) (Pı<0.001) and ICU mortality (Pı=ı0.028), compared with patients in Q2, Q3 and Q4. Patients in Q1 had signiı cantly higher cholesterol (Pı=ı0.06) and lower procalcitonin (Pı=ı0.05) at enrolment. At the extremes, patients in Q1 had decreased 28-day mortality (Pı=ı0.023) and, patients in Q4 had increased 28-day mortality, compared with the other quartiles of patients (Pı=ı0.009). Interestingly, patients in Q2 had signiı cant increased mortality compared with patients in Q1 (Pı=ı0.043), whereas the patients in Q2 had no signiı cant diı erence in 28-day mortality compared with patients in Q3. Conclusion Adverse outcomes and several potential risk factors, including organ failure, are signiı cantly associated with higher quartiles of LT concentrations. It may be useful to revise the cutoı value of lactate according to the SSC (4 mmol/l).

Activated protein C consumption and coagulation parameters in severe sepsis and septic shock.

Introduction Activated protein C (APC) deC ciency is prevalent in severe sepsis and septic shock patients. The aim of the study was to relate the anticoagulation activity evaluated by APC with other coagulation parameters adjusted to 28-day mortality. Methods A cohort study of 150 critically ill adults. Age, sex, sources of infection and coagulation markers within 24< hours from severe sepsis or septic shock onset, deC ned according to Surviving Sepsis Campaign (SSC) criteria, were studied. We analyzed APC activity using a hemostasis laboratory analyzer (BCS® XP; Siemens). A descriptive and comparative statistical analysis was performed using SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). Results We analyzed 150 consecutive episodes of severe sepsis (16%) or septic shock (84%) admitted to the UCI. The median age of the study sample was 64 (interquartile range (IQR): 22.30.001). See Figure 1. Conclusion Low levels of PC are associated with poor outcome and severity in severe sepsis, and it is well correlated with antithrombin III and INR.

Association analysis of urotensin II gene (UTS2) and flanking regions with biochemical parameters related to insulin resistance.

Background. Urotensin II (UII) is a potent vasoconstrictor peptide, which signals through a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR). UII exerts a broad spectrum of actions in several systems such as vascular cell, heart muscle or pancreas, where it inhibits insulin release. Objective. Given the reported role of UII in insulin secretion, we have performed a genetic association analysis of the UTS2 gene and flanking regions with biochemical parameters related to insulin resistance (fasting glucose, glucose 2 hours after a glucose overload, fasting insulin and insulin resistance estimated as HOMA). Results and Conclusions. We have identified several polymorphisms associated with the analysed clinical traits, not only at the UTS2 gene, but also in thePER3 gene, located upstream from UTS2. Our results are compatible with a role for UII in glucose homeostasis and diabetes although we cannot rule out the possibility that PER3 gene may underlie the reported associations.

A specific protein-enriched enteral formula decreases cortisolemia and improves plasma albumin and amino acid concentrations in elderly patients

Background: Old age is associated with an involuntary and progressive but physiological loss of muscle mass. The aim of this study was to evaluate the effects of exclusive consumption for 6 months of a protein-enriched enteral diet with a relatively high content of branched-chain amino acids on albuminemia, cortisolemia, plasma aminoacids, insulin resistance, and inflammation biomarkers in elderly patients. Methods: Thirty-two patients from the Clinical Nutrition Outpatient Unit at our hospital exclusively consumed a protein-enriched enteral diet for 6 months. Data were collected at baseline and at 3 and 6 months on anthropometric and biochemical parameters and on plasma concentrations of amino acids, cortisol,adrenocorticotropic hormone, urea, creatinine, insulin resistance, and inflammation biomarkers. Results: The percentage of patients with albumin concentration below normal cut-off values decreased from 18% to 0% by the end of the study. At 6 months, concentrations of total plasma (p = 0.008) and essential amino acids(p = 0.011), especially branched-chain amino acids (p = 0.031), were higher versus baseline values, whereas 3-methylhistidine (p = 0.001), cortisol (p = 0.001) and adrenocorticotropic hormone (p = 0.004) levels were lower. Conclusions: Regular intake of specific protein-enriched enteral formula increases plasma essential amino acids, especially branched-chain amino acids, and decreases cortisol and 3-methylhistidine, while plasma urea and creatinine remain unchanged.

Analgesic efficacy of zoledronic acid and its effect on functional status of prostate cancer patients with metastasis

Objectives: A multi-centered observational study evaluated the efficacy of zoledronic acid for improving pain and mobility, and preventing skeletal-related events (SRE) (fracture, spinal compression, pain-relieving radiotherapy), in patients with prostate cancer and bone metastasis. Materials and Methods: Males (n = 218) with prostate cancer and bone metastasis undergoing oncologic therapy received zoledronic acid (4 mg iv/month) for 6 months. Parameters evaluated were: 1) pain and movement after 2 consecutive doses; 2) quality of life; 3) SRE incidence and time-to-appearance. Medication tolerance and treatment satisfaction were assessed using a questionnaire. Results: A total of 170 that matched all the inclusion criteria (78%) out of 218 were evaluable for efficacy. There was a measurable statistically significant reduction in pain at rest and on movement as well as an improvement in the quality of life compared with baseline. Best results were obtained with early treatment. Overall incidence of bone events was 11.2%. Of the 212 patients (97.2%) evaluable for safety, 16% suffered adverse events and 66% expressed satisfaction with the treatment Discussion: Zoledronic acid is effective for reducing pain, improving mobility, and increasing the quality of life in patients with prostate cancer with bone metastasis. Its easy administration and good tolerability make zoledronic acid one of the principal therapeutic tools in the management of patients with pain associated with bone metastasis from prostate cancer.

Oxidative stress is increased in critically ill patients according to antioxidant vitamins intake, independent of severity: a cohort study

Introduction. Critically ill patients suffer from oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although ROS/RNS are constantly produced under normal circumstances, critical illness can drastically increase their production. These patients have reduced plasma and intracellular levels of antioxidants and free electron scavengers or cofactors, and decreased activity of the enzymatic system involved in ROS detoxification. The pro-oxidant/antioxidant balance is of functional relevance during critical illness because it is involved in the pathogenesis of multiple organ failure. In this study the objective was to evaluate the relation between oxidative stress in critically ill patients and antioxidant vitamin intake and severity of illness. Methods. Spectrophotometry was used to measure in plasma the total antioxidant capacity and levels of lipid peroxide, carbonyl group, total protein, bilirubin and uric acid at two time points: at intensive care unit (ICU) admission and on day seven. Daily diet records were kept and compliance with recommended dietary allowance (RDA) of antioxidant vitamins (A, C and E) was assessed. Results. Between admission and day seven in the ICU, significant increases in lipid peroxide and carbonyl group were associated with decreased antioxidant capacity and greater deterioration in Sequential Organ Failure Assessment score. There was significantly greater worsening in oxidative stress parameters in patients who received antioxidant vitamins at below 66% of RDA than in those who received antioxidant vitamins at above 66% of RDA. An antioxidant vitamin intake from 66% to 100% of RDA reduced the risk for worsening oxidative stress by 94% (ods ratio 0.06, 95% confidence interval 0.010 to 0.39), regardless of change in severity of illness (Sequential Organ Failure Assessment score). Conclusion. The critical condition of patients admitted to the ICU is associated with worsening oxidative stress. Intake of antioxidant vitamins below 66% of RDA and alteration in endogenous levels of substances with antioxidant capacity are related to redox imbalance in critical ill patients. Therefore, intake of antioxidant vitamins should be carefully monitored so that it is as close as possible to RDA.

Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients

INTRODUCTION Although several parameters have been proposed to predict the hemodynamic response to fluid expansion in critically ill patients, most of them are invasive or require the use of special monitoring devices. The aim of this study is to determine whether noninvasive evaluation of respiratory variation of brachial artery peak velocity flow measured using Doppler ultrasound could predict fluid responsiveness in mechanically ventilated patients. METHODS We conducted a prospective clinical research in a 17-bed multidisciplinary ICU and included 38 mechanically ventilated patients for whom fluid administration was planned due to the presence of acute circulatory failure. Volume expansion (VE) was performed with 500 mL of a synthetic colloid. Patients were classified as responders if stroke volume index (SVi) increased >or= 15% after VE. The respiratory variation in Vpeakbrach (DeltaVpeakbrach) was calculated as the difference between maximum and minimum values of Vpeakbrach over a single respiratory cycle, divided by the mean of the two values and expressed as a percentage. Radial arterial pressure variation (DeltaPPrad) and stroke volume variation measured using the FloTrac/Vigileo system (DeltaSVVigileo), were also calculated. RESULTS VE increased SVi by >or= 15% in 19 patients (responders). At baseline, DeltaVpeakbrach, DeltaPPrad and DeltaSVVigileo were significantly higher in responder than nonresponder patients [14 vs 8%; 18 vs. 5%; 13 vs 8%; P < 0.0001, respectively). A DeltaVpeakbrach value >10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%. A DeltaPPrad value >10% and a DeltaSVVigileo >11% predicted volume responsiveness with a sensitivity of 95% and 79%, and a specificity of 95% and 89%, respectively. CONCLUSIONS Respiratory variations in brachial artery peak velocity could be a feasible tool for the noninvasive assessment of fluid responsiveness in patients with mechanical ventilatory support and acute circulatory failure. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT00890071.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: Effects on leptin and TNF-alpha.

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: A 12-month, double-blind, parallel clinical trial

OBJECTIVE Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.

N-3 fatty acids, cancer and cachexia: a systematic review of the literature.

Use of n-3 fatty acids (FA) has been reported to be beneficial for cancer patients. We performed a systematic review of the literature in order to issue recommendations on the clinical use of n-3 FA in the cancer setting. A systematic search was performed in MEDLINE, EMBASE, Cochrane and Healthstar databases. We selected clinical trials or prospective observational studies including patients with cancer and life expectancy >2 months, in which enteral supplements with n-3 FA were administered. Parameters evaluated individually were clinical (nutritional status, tolerance, survival and hospital stays), biochemical (inflammatory mediators), and functional (functional status, appetite and quality of life (QoL)). Seventeen studies met the inclusion criteria; eight were of high quality. The panel of experts established the following evidence: (1) oral supplements with n-3 FA benefit patients with advanced cancer and weight loss, and are indicated in tumours of the upper digestive tract and pancreas; (2) the advantages observed were: increased weight and appetite, improved QoL, and reduced post-surgical morbidity; (3) there is no defined pattern for combining different n-3 FA, and it is recommended to administer > 1.5 g/day; and (4) better tolerance is obtained administering low-fat formulas for a period of at least 8 weeks. All the evidences were grade B but for 'length of treatment' and 'advantage of survival' it was grade C. Our findings suggest that administration of n-3 FA (EPA and DHA) in doses of at least 1.5 g/day for a prolonged period of time to patients with advanced cancer is associated with an improvement in clinical, biological and QoL parameters.

Breast cancer prognostic classification in the molecular era: the role of histological grade.

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers.

Efectos de la suplementación con glutamina sobre el sistema antioxidante y la peroxidación lipídica en pacientes críticos con nutrición parenteral

INTRODUCTION In the critically ill patient, there is a continuous production of reactive oxygen species (ROS) that need to be neutralized to prevent oxidative stress (OS). Quantitatively speaking, the glutathione system (GSH) is the most important anti-oxidant endogenous defense. To increase it, glutamine supplementation has been shown to be effective by protecting against the oxidative damage and reducing the morbimortality. OBJECTIVE To assess the effect of adding an alanylglutamine dipeptide to PN on lipid peroxidation lipidica and glutathione metabolism, as well as its relationship with morbidity in critically ill patients. METHODS Determination through spectrophotometry techniques of glutathione peroxidase, glutathione reductase, total glutathione, and maloniladdehyde at admission adn after seven days of hospitalization at the Intensive Care Unit (ICU) in 20 patients older than 18 years on parenteral nutrition therapy. RESULTS The group of patients receiving parenteral nutrition with glutamine supplementation had significant increases in total glutathione (42.35+/-13 vs 55.29+/-12 micromol/l; p<0.05) and the enzymatic activity of glutathione peroxidasa (470+/-195 vs 705+/-214 micromol/l; p<0.05) within one week of nutritional therapy, whereas the group on conventional parenteral nutrition did not show significant changes of any of the parameters studied (p>0.05). However, both mortality and ICU stay were not different between the study group, whereas the severity (assessed by the SOFA score) was lower in the group of patients receiving glutamine (SOFA 5+/-2 vs 8+/-1.8; p<0.05). CONCLUSIONS Glutamine intake in critically ill patients improves the antioxidant defenses, which leads to lower lipid peroxidation and lower morbidity during admission at the ICU.

Evolución de parámetros bioquímicos nutricionales en pacientes de hemodiálisis durante un año de seguimiento

Current high survival in hemodialysis patients (52% at 5 years) have made the chronic manifestations to emerge such as the high hyponutrition prevalence of these patients, as well as the importance of the nutritional status in their morbimortality. The reason for protein-caloric hyponutrition is multifactorial, although chronic inflammatory conditions associated to the dialysis technique are becoming more and more relevant. The variations in several nutritional biochemical parameters (total proteins, plasma albumin, transferrin, and total cholesterol) have been assessed in 73 hemodialysis patients for one year. The mean age of the patients was 53.3 +/- 18.69 years (43 males and 30 females). The average on hemodialysis program was 43 +/- 33 months, with a mean session duration of 246 +/- 24 minutes, and mean hemodialysis dose administered of 1.37 +/- 0.27 (KT/V) (second generation Daurgidas). A decrease in all the biochemical parameters assessed has been observed, with statistically significant differences: total proteins (p < 0.001), albumin (p < 0.00001), total cholesterol (p < 0.05), and transferrin (p < 0.01). The evolution of the nutritional biochemical parameters assessed showed an important nutritional deterioration of the patients remaining stable with the therapy.

Estudio longitudinal del Índice de masa corporal (IMC) en pacientes en diálisis

Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years, 43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data.