Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery: A prospective observational study.

BACKGROUND: Patients admitted to intensive care unit (ICU) after cardiac surgery develop acute kidney injury (AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome. AIM: To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome. METHODS: This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome. Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development. RESULTS: After ICU admission, 55 patients (26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore II (OR: 1.18; 95%CI: 1.06-1.31, P = 0.003), white blood cells (WBC) pre-operatively (OR: 1.0; 95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease (OR: 2.82; 95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113 (777-2195) vs 714 (511-1020) min, P = 0.0001] and ICU length of stay [70 (28-129) vs 26 (21-51) h, P = 0.0001], higher rate of ICU-acquired weakness (16.4% vs 5.3%, P = 0.015), reintubation (10.9% vs 1.3%, P = 0.005), dialysis (7% vs 0%, P = 0.005), delirium (36.4% vs 23.8%, P = 0.001) and mortality (3.6% vs 0.7%, P = 0.046). CONCLUSION: Patients present frequently with AKI after cardiac surgery. EuroScore II, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Ex Vivo Evaluation of Glutamine Treatment in Sepsis and Trauma in a Human Peripheral Blood Mononuclear Cells Model.

We aimed to assess the lipopolysaccharide (LPS), or heat shock (HS) induction, and glutamine-modulating effects on heat shock protein-90α (HSP90α) and cytokines in an ex vivo model using peripheral blood mononuclear cells (PBMCs). The PBMCs of patients with septic shock, trauma-related systemic inflammatory response syndrome (SIRS), and healthy subjects were incubated with 1 µg/mL LPS at 43 °C (HS). Glutamine 10 mM was added 1 hour before or after induction or not at all. We measured mRNA HSP90α, monocyte (m) and lymphocyte (l) HSP90α proteins, interleukin (IL)-1b, -6, -8, -10, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) supernatant levels. Heat shock increased the HSP90α mRNA and mHSP90α in all groups (10-fold in sepsis, p < 0.001 and p = 0.047, respectively). LPS induced the mHSP90α and lHSP90α in healthy (p < 0.001) and mHSP90α in SIRS (p = 0.004) but not in sepsis. LPS induced the cytokines at 24 and 48 h in all groups, especially in trauma (p < 0.001); HS only induced the IL-8 in healthy (p = 0.003) and septic subjects (p = 0.05). Glutamine at 10 mM before or after stimulation did not alter any induction effect of LPS or HS on HSP90α mRNA and mHSP90α protein in sepsis. In SIRS, glutamine before LPS decreased the mHSP90α but increased it when given after HS (p = 0.018). Before or after LPS (p = 0.049) and before HS (p = 0.018), glutamine decreased the lHSP90α expression in sepsis but increased it in SIRS when given after HS (p = 0.003). Regarding cytokines, glutamine enhanced the LPS-induced MCP-1 at 48 h in healthy (p = 0.011), SIRS (p < 0.001), and sepsis (p = 0.006). In conclusion, glutamine at 10 mM, before or after LPS and HS, modulates mHSP90α and lHSP90α in sepsis and SIRS differently and unpredictably. Although it does not alter the stimulation effect on interleukins, glutamine enhances the LPS induction effect on supernatant MCP-1 in all groups. Future research should seek to elucidate better the impact of glutamine and temperature modulation on HSP90α and MCP-1 pathways in sepsis and trauma.

The effectiveness of the active cycle of breathing technique in patients with chronic respiratory diseases: A systematic review.

BACKGROUND: Active cycle breathing technique (ACBT), which includes cycle of breathing control, thoracic expansion exercises and forced expiratory technique (FET), appears to have beneficial effects in patients with a variety of respiratory diseases. This systematic review provides an update on the new related studies, expanding the evidence base through the last 12 years and specifically evaluating the effectiveness of ACBT on pulmonary function-related outcome variables in patients with chronic respiratory diseases. METHODS: MEDLINE/Pubmed, PEDro, and Cochrane Library for Randomized Controlled Trials were searched between September 2008 and December 2021, in continuance of a previous systematic review, to identify randomized clinical trials and/or crossover studies comparing ACBT to other respiratory treatment techniques in patients with chronic obstructive pulmonary diseases, cystic fibrosis, or bronchiectasis. RESULTS: Eleven studies were included and the quality of most of them was moderate to good. The outcomes most frequently assessed were forced expiratory volume in 1 s (FEV1), sputum wet weight, forced vital capacity (FVC), and peak expiratory flow rate. Secondary outcomes were quality of life and dyspnea. Various comparators were identified and most of them assessed the ACBT as an effective method in comparison with other respiratory treatment modalities. Most studies revealed that ACBT/FET had at least an equally beneficial short-term effect on sputum wet weight, FEV1 and FVC compared to other treatment methods. CONCLUSION: The results of this updating review reinforced the data of a previous systematic review regarding the beneficial impact of ACBT for the short-term improvement in respiratory tract secretions clearance and pulmonary function. ACBT is effective in increasing the expectorated sputum volume, in reducing viscoelasticity of the secretion and in relieving symptoms such as dyspnea.

Impact of supervised aerobic exercise on clinical physiological and mental parameters of people living with HIV: a systematic review and meta-analyses of randomized controlled trials.

Background: The benefits derived from supervised aerobic exercise in people living with human immunofeficiency virus- HIV (PLWH) have not yet been clearly identified.Objective: To evaluate the impact of supervised aerobic exercise on immunological, cardiorespiratory, pulmonary, hemodynamic and mental parameters of PLWH.Methods: A systematic review was carried out in accordance to PRISMA guidelines. PubMed, Physiotherapy Evidence Database (PEDro) and Cochrane Central Register of Controlled Trials (CENTRAL) were screened up to August 2021, for the identification of English written randomized trials, with participants aged 18 years and older, at any stage of the disease, with or without co-morbidities. The risk of bias assessment was conducted according to the Cochrane Collaboration's tool for assessing risk of bias. Meta- analyses were conducted using continuous, inverse variance, random-effects model.Results: Ten studies were suitable for meta-analysis based on inclusion criteria. Supervised aerobic exercise appeared to have beneficial effects on depressive symptoms [mean difference (MD)= -4.18 (confidence interval (CI)= (-6.55)-(-1.81), Z = 3.46, p = 0.0005, I2=0%, n = 2], forced expiratory volume in 1 sec [MD = 0.70, CI = 0.39-1.00, Z = 4.41, p < 0.0001, I2=0%, n = 2], and on the maximum oxygen uptake [MD = 1.38, CI = -0.02-2.78, Z = 1.94, p = 0.05, I2=94%, n = 4] of PLWH. No exercise effect was found for CD4 T-cell count (p = 0.16, n = 5), systolic blood pressure (p = 0.91, n = 2) and diastolic blood pressure (p = 0.72, n = 2).Conclusions: Supervised continuous aerobic exercise may improve lung function, depressive symptomatology and aerobic capacity of PLWH, however, the small number of available studies and the high heterogeneity concerning VO2max demonstrate the need for more research in this area.

Exercise training in heart transplantation.

Heart transplantation remains the gold standard in the treatment of end-stage heart failure (HF). Heart transplantation patients present lower exercise capacity due to cardiovascular and musculoskeletal alterations leading thus to poor quality of life and reduction in the ability of daily self-service. Impaired vascular function and diastolic dysfunction cause lower cardiac output while decreased skeletal muscle oxidative fibers, enzymes and capillarity cause arteriovenous oxygen difference, leading thus to decreased peak oxygen uptake in heart transplant recipients. Exercise training improves exercise capacity, cardiac and vascular endothelial function in heart transplant recipients. Pre-rehabilitation regular aerobic or combined exercise is beneficial for patients with end-stage HF awaiting heart transplantation in order to maintain a higher fitness level and reduce complications afterwards like intensive care unit acquired weakness or cardiac cachexia. All hospitalized patients after heart transplantation should be referred to early mobilization of skeletal muscles through kinesiotherapy of the upper and lower limbs and respiratory physiotherapy in order to prevent infections of the respiratory system prior to hospital discharge. Moreover, all heart transplant recipients after hospital discharge who have not already participated in an early cardiac rehabilitation program should be referred to a rehabilitation center by their health care provider. Although high intensity interval training seems to have more benefits than moderate intensity continuous training, especially in stable transplant patients, individualized training based on the abilities and needs of each patient still remains the most appropriate approach. Cardiac rehabilitation appears to be safe in heart transplant patients. However, long-term follow-up data is incomplete and, therefore, further high quality and adequately-powered studies are needed to demonstrate the long-term benefits of exercise training in this population.

Exercise Training Enhances Angiogenesis-Related Gene Responses in Skeletal Muscle of Patients with Chronic Heart Failure.

Peripheral myopathy consists of a hallmark of heart failure (HF). Exercise enhanced skeletal muscle angiogenesis, and thus, it can be further beneficial towards the HF-induced myopathy. However, there is limited evidence regarding the exercise type that elicits optimum angiogenic responses of skeletal muscle in HF patients. This study aimed to (a) compare the effects of a high-intensity-interval-training (HIIT) or combined HIIT with strength training (COM) exercise protocol on the expression of angiogenesis-related factors in skeletal muscle of HF patients, and (b) examine the potential associations between the expression of those genes and capillarization in the trained muscles. Thirteen male patients with chronic HF (age: 51 ± 13 y; BMI: 27 ± 4 kg/m2) were randomly assigned to a 3-month exercise program that consisted of either HIIT (N = 6) or COM training (N = 7). Vastus lateralis muscle biopsies were performed pre- and post-training. RT-PCR was used to quantify the fold changes in mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1 alpha (HIF-1α), angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), angiopoietin receptor (Tie2), and matrix metallopeptidase 9 (MMP-9), and immunohistochemistry to assess capillarization in skeletal muscle post-training. There was an overall increase in the expression levels of VEGF, VEGFR-2, HIF-1α, Ang2, and MMP9 post-training, while these changes were not different among groups. Changes in capillary-to-fibre ratio were found to be strongly associated with Tie2 and HIF-1α expression. This was the first study demonstrating that both HIIT and combined HIIT with strength training enhanced similarly the expression profile of angiogenic factors in skeletal muscle of HF patients, possibly driving the angiogenic program in the trained muscles, although those gene expression increases were found to be only partially related with muscle capillarization.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

Effects of High-Intensity Interval Exercise Training on Skeletal Myopathy of Chronic Heart Failure.

BACKGROUND: It remains controversial which type of exercise elicits optimum adaptations on skeletal myopathy of heart failure (HF). Our aim was to evaluate the effect of high-intensity interval training (HIIT), with or without the addition of strength training, on skeletal muscle of HF patients. METHODS AND RESULTS: Thirteen male HF patients (age 51 ± 13 years, body mass index 27 ± 4 kg/m2) participated in either an HIIT (AER) or an HIIT combined with strength training (COM) 3-month program. Biopsy samples were obtained from the vastus lateralis. Analyses were performed on muscle fiber type, cross-section area (CSA), capillary density, and mRNA expression of insulin-like growth factor (IGF) 1 isoforms (ie, IGF-1Ea, IGF-1Eb, IGF-1Ec), type-1 receptor (IGF-1R), and binding protein 3 (IGFBP-3). Increased expression of IGF-1Ea, IGF-1Eb, IGF-1Ec, and IGFBP-3 transcripts was found (1.7 ± 0.8, 1.5 ± 0.8, 2.0 ± 1.32.4 ± 1.4 fold changes, respectively; P < .05). Type I fibers increased by 21% (42 ± 10% to 51 ± 7%; P < .001) and capillary/fiber ratio increased by 24% (1.27 ± 0.22 to 1.57 ± 0.41; P = .005) in both groups as a whole. Fibers' mean CSA increased by 10% in total, but the increase in type I fibers' CSA was greater after AER than COM (15% vs 6%; P < .05). The increased CSA correlated with the increased expression of IGF-1Ea and IGF-1Εb. CONCLUSIONS: HIIT reverses skeletal myopathy of HF patients, with the adaptive responses of the IGF-1 bioregulation system possibly contributing to these effects. AER program seemed to be superior to COM to induce muscle hypertrophy.

Lifestyle intervention and one-year prognosis of patients following open heart surgery: a randomised clinical trial.

AIMS AND OBJECTIVES: To evaluate the one-year prognosis of a lifestyle counselling intervention (diet, smoking cessation and exercise) among patients who had open heart surgery. BACKGROUND: Cardiovascular disease is the leading cause of morbidity worldwide in both developing and developed countries. Lifestyle modification plays an important role for patients who are at a high risk of developing cardiovascular disease and for those with an established cardiovascular disease. DESIGN: Randomised, nonblind and lifestyle counselling intervention study with a one-year follow-up. METHODS: A randomised, nonblind intervention study was performed on 500 patients who had open heart surgery. After hospital discharge, 250 patients (intervention group) were randomly allocated lifestyle counselling according to the recent guidelines provided by the European Society of Cardiology (European Journal Preventive Cardiology, 19, 2012, 585). The remaining 250 patients (control group) received the regular instructions. Primary end-point was the development of a cardiovascular disease (nonfatal event) during the first year; secondary end-points included fatal events, smoking abstinence, dietary habits and a physical activity evaluation. RESULTS: According to the primary end-point, the odds of having a nonfatal cardiovascular disease event are 0·56-times (95%CI 0·28, 0·96, p = 0·03) lower for the intervention group compared to the control group. One-year after surgery, it was found that participants in the intervention group were 1·96-times (95%CI 1·31, 2·93, p < 0·001) more likely to achieve dietary recommendations, 3·32-times (95%CI 2·24, 4·91, p < 0·001) more likely to achieve physical activity recommendations and 1·34-times (95%CI 1·15, 1·56, p < 0·001) more likely to return to work. CONCLUSION: Lifestyle counselling intervention following open heart surgery can improve health outcomes and reduce the risk of a new cardiac event. Health care services must recommend and organise well-structured cardiac rehabilitation programmes adjusted to the patient's needs. RELEVANCE TO CLINICAL PRACTICE: A well-structured cardiac rehabilitation programme adjusted to the patient's profile is a safe and cost-effective way to improve patients' outcome.

Prolonged Oxygen Kinetics During Constant Workload Submaximal Exercise Is Associated With Disease Severity in Adult Subjects With Cystic Fibrosis.

BACKGROUND: The goal of this study was to explore the relation between oxygen kinetics during constant work load submaximal cardiopulmonary exercise test (CPET) and disease severity in adult subjects with cystic fibrosis. METHODS: Fourteen adult subjects with cystic fibrosis (CF; 8 males, 22 ± 4 y old) and a mean Schwachman score of 73 ± 11 and 10 healthy individuals (5 males, 29 ± 4 y old) underwent pulmonary function tests at rest, maximal and constant work load submaximal CPET on a cycloergometer. Breath-by-breath analysis was used for measuring oxygen kinetic parameters and the time constant (tau), expressing phase 2 of submaximal CPET. RESULTS: Subjects with CF had a significantly prolonged tau compared with healthy subjects (42.3 ± 21.5 vs. 29.3 ± 6.4, s, P < .05). The tau during phase 2 was inversely correlated with FEV1(% pred) (r = -0.77, P = .001), breathing reserve (r = -0.74, P = .003), V̇O2peak (r = -0.53, P = .049), V̇O2/t slope (r = -0.58, P = .03), and Schwachman score (r = -0.80, P = .001). In a multivariate regression model including all the above variables, the Schwachman score (ß = -0.697, P = .002) emerged as independent predictor of tau (R2 = 0.719, P = .001). CONCLUSIONS: We conclude that adult subjects with CF present significant prolonged oxygen kinetics during constant work load submaximal exercise in relation to disease severity. Thus, submaximal exercise should be considered the preferable CPET choice in adult patients with severe CF.

Prediction of the renal replacement therapy requirement in mechanically ventilated critically ill patients by combining biomarkers for glomerular filtration and tubular damage.

PURPOSE: Mechanically ventilated critically ill patients with high severity score indices need a very cautious therapeutic approach. Considering that inappropriate decisions on renal replacement therapy (RRT) initiation may promote unwanted adverse effects, we evaluated whether a panel of novel and traditional renal markers is superior to conventional renal marker in predicting RRT requirements in this group of patients. METHODS: This was a prospective observational study, performed at the two distinct multidisciplinary intensive care units (ICUs) of a 1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled the inclusion criteria of the study. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were determined on ICU admission. The predictive performance of all markers for first RRT was tested and compared based on the area under the receiver operating characteristic (ROC) curves. Time-dependent ROC curves were used to assess the earlier time point where the markers presented their maximum area under the curve (AUC). RESULTS: All studied biomarkers and acute physiology and chronic health evaluation (APACHE) II score, were significant independent predictors of RRT (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC and sCr showed early maximum predictive ability within 10 days of ICU admission, while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients without acute kidney injury (AKI) on ICU entry, the combination of sCysC and APACHE II score proved best (AUC-ROC=0.78). CONCLUSIONS: Specific markers of kidney dysfunction and of kidney damage can be successfully combined to increase the prognostic capability for RRT initiation. The presence of AKI affects diagnostic performance. Without an established AKI on ICU admission, future RRT requirement was better predicted by the combination of illness severity with a marker of glomerular filtration rate. With AKI on ICU admission a combination of the marker of glomerular filtration rate with one of tubular injury proved best.

Exercise intolerance in chronic heart failure: the role of cortisol and the catabolic state.

Chronic heart failure (CHF) is a complex clinical syndrome leading to exercise intolerance due to muscular fatigue and dyspnea. Hemodynamics fail to explain the reduced exercise capacity, while a significant skeletal muscular pathology seems to constitute the main underlying mechanism for exercise intolerance in CHF patients. There have been proposed several metabolic, neurohormonal and immune system abnormalities leading to an anabolic/catabolic imbalance that plays a central role in the pathogenesis of the wasting process of skeletal muscle myopathy. The impairment of the anabolic axes is associated with the severity of symptoms and the poor outcome in CHF, whereas increased cortisol levels are predictive of exercise intolerance, ventilatory inefficiency and chronotropic incompetence, suggesting a significant contributing mechanism to the limited functional status. Exercise training and device therapy could have beneficial effects in preventing and treating muscle wasting in CHF. However, specific anabolic treatment needs more investigation to prove possible beneficial effects.

Inappropriately normal plasma ACTH and cortisol concentrations in the face of increased circulating interleukin-6 concentration in exercise in patients with sarcoidosis.

Sarcoidosis is an autoimmune disease, and hypothalamic-pituitary-adrenal (HPA) axis activity is blunted in autoimmunity. Exercise stimulates the HPA axis, and we hypothesized that in sarcoidosis patients responses to treadmill exercise would be reduced. Hence, we studied 44 sarcoidosis patients [27 untreated (age, mean ± SD, 42 ± 2 years, 12 males, 15 females) and 17 dexamethasone treated (age, 46 ± 4 years, 7 males, 10 females)] and 20 healthy controls (40 ± 5 years old, 9 males, 11 females). Blood samples were drawn before, at peak (exhaustion), and 15 min after treadmill exercise for adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor (TNF), interleukin-1ß (IL-1ß) and IL-6 measurements. At peak, plasma ACTH (pg/ml) was increased in untreated (mean ± SE, ΔACTH = 162.8 ± 29.9) and treated (ΔACTH = 123.3 ± 48.1) patients and controls (ΔACTH = 112.3 ± 41.7). Post-exercise, cortisol (ng/ml) was increased (p < 0.05) in untreated patients (Δcortisol = 48.4 ± 14.7) and controls (Δcortisol = 46.0 ± 15.9), but not significantly in treated patients (Δcortisol = 1.43 ± 2.56). At baseline, serum IL-6 (pg/ml) and TNF (pg/ml) were higher in untreated (3.02 ± 0.54 and 3.89 ± 0.72) and treated (1.75 ± 0.33 and 2.16 ± 1.00) patients, respectively, than in controls (0.80 ± 0.66 and 1.58 ± 0.32). At peak exercise, IL-6 was increased in untreated (ΔIL-6 = 0.96 ± 0.14) and treated (ΔIL-6 = 0.91 ± 0.47) patients and controls (ΔIL-6 = 0.96 ± 0.18); IL-1ß was increased only in controls. Hence, the HPA axis of untreated sarcoidosis patients and controls responded similarly to treadmill exercise. In sarcoidosis patients, increased IL-6 was associated with HPA stimulation. Cortisol concentrations were similar between patients and controls, although IL-6 concentrations were higher in patients. Thus, in the face of chronically elevated IL-6 levels in sarcoidosis, there may be dysfunctional IL-6-induced HPA responses or HPA adaptation to high IL-6 concentrations.

Combination of renal biomarkers predicts acute kidney injury in critically ill adults.

OBJECTIVE: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. METHODS: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL + sCr and pNGAL + uNGAL + sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p = 0.04). Their NRI (0.78, p = 0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p = 0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. CONCLUSION: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.

Sonographic and clinical features of upper extremity deep venous thrombosis in critical care patients.

Background-Aim. Upper extremity deep vein thrombosis (UEDVT) is an increasingly recognized problem in the critically ill. We sought to identify the prevalence of and risk factors for UEDVT, and to characterize sonographically detected thrombi in the critical care setting. Patients and Methods. Three hundred and twenty patients receiving a subclavian or internal jugular central venous catheter (CVC) were included. When an UEDVT was detected, therapeutic anticoagulation was started. Additionally, a standardized ultrasound scan was performed to detect the extent of the thrombus. Images were interpreted offline by two independent readers. Results. Thirty-six (11.25%) patients had UEDVT and a complete scan was performed. One (2.7%) of these patients died, and 2 had pulmonary embolism (5.5%). Risk factors associated with UEDVT were presence of CVC [(odds ratio (OR) 2.716, P = 0.007)], malignancy (OR 1.483, P = 0.036), total parenteral nutrition (OR 1.399, P = 0.035), hypercoagulable state (OR 1.284, P = 0.045), and obesity (OR 1.191, P = 0.049). Eight thrombi were chronic, and 28 were acute. We describe a new sonographic sign which characterized acute thrombosis: a double hyperechoic line at the interface between the thrombus and the venous wall; but its clinical significance remains to be defined. Conclusion. Presence of CVC was a strong predictor for the development of UEDVT in a cohort of critical care patients; however, the rate of subsequent PE and related mortality was low.

Microcirculation and macrocirculation in cardiac surgical patients.

Background. The aim of our study was to investigate the relationship between microcirculatory alterations after open cardiac surgery, macrohemodynamics, and global indices of organ perfusion. Methods. Patients' microcirculation was assessed with near-infrared spectroscopy (NIRS) and the vascular occlusion technique (VOT). Results. 23 patients undergoing open cardiac surgery (11 male/12 female, median age 68 (range 28-82) years, EuroSCORE 6 (1-12)) were enrolled in the study. For pooled data, CI correlated with the tissue oxygen consumption rate as well as the reperfusion rate (r = 0.56, P < 0.001 and r = 0.58, P < 0.001, resp.). In addition, both total oxygen delivery (DO(2), mL/min per m(2)) and total oxygen consumption (VO(2), mL/min per m(2)) also correlated with the tissue oxygen consumption rate and the reperfusion rate. The tissue oxygen saturation of the thenar postoperatively correlated with the peak lactate levels during the six hour monitoring period (r = 0.50, P < 0.05). The tissue oxygen consumption rate (%/min) and the reperfusion rate (%/min), as derived from the VOT, were higher in survivors compared to nonsurvivors for pooled data [23 (4-54) versus 20 (8-38) P < 0.05] and [424 (27-1215) versus 197 (57-632) P < 0.01], respectively. Conclusion. Microcirculatory alterations after open cardiac surgery are related to macrohemodynamics and global indices of organ perfusion.

Acute effects of smoking on skeletal muscle microcirculation monitored by near-infrared spectroscopy.

BACKGROUND: Cigarette smoking predisposes to vascular disease. Our study aimed to assess the acute effects of cigarette smoking on peripheral microcirculation using near-infrared spectroscopy (NIRS) and to compare microcirculatory function of smokers with that of nonsmokers. METHODS: We examined 65 healthy volunteers: 25 smokers (14 men and 11 women; age range, 20 to 27 years) and 40 nonsmokers (31 men and 9 women; age range, 19 to 38 years). Smokers had refrained from smoking for 2 h prior to the examination. Tissue O(2) saturation (Sto(2)), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured with a probe placed on the thenar muscle. Sto(2) baseline values were recorded for 5 min. Subsequently, the brachial artery occlusion technique was applied to evaluate microcirculatory function before, during, and after smoking one cigarette. RESULTS: Sto(2) before smoking was 85 +/- 6% (mean +/- SD), not differing significantly between men and women (84.4 +/- 6.6% vs 85.6 +/- 5.8%, respectively; p = 0.721). Sto(2) did not change significantly during smoking. O(2) consumption rate was significantly greater in women (33.4 +/- 6.7 Sto(2) U/min vs 25.7 +/- 7.1 Sto(2) U/min, p = 0.032) at baseline and throughout the smoking session. O(2) consumption rate was reduced during smoking (p < 0.001) and at 5 min after the smoking session. Smoking had a significant effect on vascular reactivity (p = 0.015), with no significant differences between genders. Five minutes after smoking, vascular reactivity had returned to approximately normal levels. CONCLUSION: Smoking acutely affects microcirculatory function. NIRS is a noninvasive, operator-independent technique that can document these effects. It seems promising for the prospective evaluation of the effects of long-term exposure to cigarette smoke.