Antonio León-Justel

Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults

S100B is a calcium-binding protein released into the blood from astroglial cells due to brain injury. Some authors have described a correlation between S100B serum concentration and severity of brain damage. There is not much information about the accuracy of urinary S100B for predicting outcome after severe traumatic brain injury (TBI). 55 patients with severe TBI were included in the study. Blood and urine samples were drawn to determine S100B levels on admission and on the subsequent 24, 48, 72 and 96 h. S100B concentrations (serum and urine) were significantly higher in patients who were dead a month after the accident compared to survivors. ROC-analysis showed that S100B at 24h post-severe TBI is a useful tool for predicting mortality (serum: AUC 0.958, urine: AUC 0.778). The best cut-offs for S100B were 0.461 μg/L and 0.025 μg/L (serum and urine respectively), with a sensitivity of 90% for both measurements and a specificity of 88.4% (serum) and 62.8% (urine). We can state that the determination of S100B levels both in urine and serum acts as a sensitive and an effective biomarker for the early prediction of mortality after severe TBI.

Introduction of Fibrinogen in the Treatment of Hemostatic Disorders During Orthotopic Liver Transplantation: Implications in the Use of Allogenic Blood

BACKGROUND Orthotopic liver transplantation (OLT) requires a large amount of blood-derived resources. The indications for their availability in the surgery area is based on empirical protocols. The implementation of point-of-care apparatuses gives rise to the detection of hemostatic alterations due to functional deficits of fibrinogen. METHODS To monitor coagulation disorders and other biochemical parameters, we used thromboelastometry (ROTEM®) and a MovlLab® unit, respectively. We evaluated the stability and firmness of the clot based on fibrin (FibTem test). The measurements were performed during all of the liver transplant stages: baseline, anhepatic, and reperfusion. Fibrinogen (hemocompletan) was administered to achieve maximum clot firmness, based on patient weight and the existence of surgical bleeding. This pilot cohort of 20 transplant patients (group B) compared outcomes with the 59 patients from the previous year (group A). RESULTS Haemocompletan was administered to 45% of the 20 patients. The ratio of red blood cell components per patient diminished from 8.4 to 3.9 (53% reduction) and, fresh frozen plasma from 5.6 to 1.9 (65% reduction). Transfusions of platelet concentrates decreased by 50% with a ratio of 1.5-0.7 per patient. Likewise, 20% of transplant patients received no transfusions of blood products compared with 3.5% in the previous period. CONCLUSION The incorporation of fibrinogen into the treatment of hemostatic disorders in OLT leads to a reduced use of allogenic blood products. We observed reduced number of patients who received transfusions, while those who underwent transfusion did so to a lesser degree.

S100B Protein May Detect Brain Death Development after Severe Traumatic Brain Injury

Despite improvements in the process of organ donation and transplants, the number of organ donors is progressively declining in developed countries. Therefore, the early detection of patients at risk for brain death (BD) is a priority for transplant teams seeking more efficient identification of potential donors. In the extensive literature on S100B as a biomarker for traumatic brain injury (TBI), no evidence appears to exist on its prognostic capacity as a predictor of BD after severe TBI. The objective of this study is to assess the value of including acute S100B levels in standard clinical data as an early screening tool for BD after severe TBI. This prospective study included patients with severe TBI (Glasgow Coma Scale score [GCS] ≤ 8) admitted to our Neurocritical Care Unit over a 30 month period. We collected the following clinical variables: age, gender, GCS score, pupillary alterations at admission, hypotension and pre-hospital desaturation, CT scan results, isolated TBI or other related injuries, Injury Severity Score (ISS), serum S100B levels at admission and 24 h post-admission, and a final diagnosis regarding BD. Of the 140 patients studied, 11.4% developed BD and showed significantly higher S100B concentrations (p<0.001). Multivariate analysis showed that bilateral unresponsive mydriasis at admission and serum S100B at 24 h post-admission had odds ratios (ORs) of 21.35 (p=0.005) and 4.9 (p=0.010), respectively. The same analysis on patients with photomotor reflex in one pupil at admission left only the 24 h S100B sample in the model (OR=15.5; p=0.009). Receiver operating characteristics (ROC) curve analysis on this group showed the highest area under the curve (AUC) (0.86; p=0.001) for 24 h S100B determinations. The cut off was set at 0.372 μg/L (85.7% sensitivity, 79.3% specificity, positive predictive value [PPV]=18.7% and negative predictive value [NPV]=98.9%). This study shows that pupillary responsiveness at admission, as well as 24 h serum S100B levels, could serve as screening tools for the early detection of patients at risk for BD after severe TBI.

A clinical profile of memory impairment in humans due to endogenous glucocorticoid excess

Objective  Glucocorticoid excess is commonly related to neuropsychiatric and neurological disorders, with memory impairment typically found among these disorders. The objective of this study is to offer a clinical profile of memory deficits resulting from exposure to chronic stress‐level elevations of endogenous glucocorticoids in patients with Cushings Syndrome (CS).

Point-of-care haemostasis monitoring during liver transplantation reduces transfusion requirements and improves patient outcome.

BACKGROUND Optimal haemostasis management can improve patient outcomes and reduce blood loss and transfusion volume in orthotopic-liver-transplant (OLT). METHODS We performed a prospective study including 200 consecutive OLTs. The first 100 patients were treated according to the clinics standards and the next 100 patients were treated using the new point-of-care (POC)-based haemostasis management strategy. Transfusion parameters and other outcomes were compared between groups. RESULTS Transfusion requirements were reduced in the POC group. The median and IQR of red-blood-cells (RBC) transfusion units were reduced from 5 [2-8] to 3 [0-5] (p < 0.001), plasma from 2 [0-4] to 0 (p < 0.001), and platelets from 1 [0-4] to 0 [0-1] (p < 0.001), into the POC group only four patients received tranexamic acid and fibrinogen transfusion rate was 1.13 ± 1.44 g (p = 0.001). We also improved the incidence of transfusion avoidance, 5% vs. 24% (p < 0.001) and reduced the incidence of massive transfusion (defined as the transfusion of more than 10 RBC units), 13% vs. 2% (p = 0.005). We also observed a relationship between RBC transfusion requirements and preoperative haemoglobin, and between platelet transfusion and preoperative fibrinogen levels. The incidence of postoperative complications, such as, reoperation for bleeding, acute-kidney-failure or haemodynamic instability was significantly lower (13.0% vs. 5%, p = 0.048, 17% vs. 2%, p < 0.001, and 29% vs. 16%, p = 0.028). Overall, blood product transfusion was associated with increased risk of postoperative complications. CONCLUSIONS A haemostatic therapy algorithm based on POC monitoring reduced transfusion and improved outcome in OLT.

Modelo experimental de lesión cerebral tipo masa en rata: expresión del daño cerebral mediante enolasa neuroespecífica y proteína S100B

OBJECTIVE To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the induced brain injury. DESIGN An experimental study with a control group. SETTING Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS Fourteen adult Wistar rats. INTERVENTIONS Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 μl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation. PRIMARY STUDY VARIABLES Weight, early mortality, serum NSE and S100B concentration. RESULTS Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker. CONCLUSIONS Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.

Budget impact of using midnight salivary cortisol in the diagnosis of hypercortisolism

BACKGROUND A single midnight serum cortisol (MSC) test has been reported to possess the best sensitivity and specificity for diagnosing Cushings syndrome (CS). However, this test requires patient hospitalization, making it costly. This paper aims to compare the hospital budget impact and accuracy of using midnight salivary cortisol (MSVC), as opposed to MSC, in the diagnosis of hypercortisolism. METHODS 77 patients with at least two high urinary free cortisol (UFC) values (>360 nmol/24 h) were selected from 611 patients with clinical symptoms of CS. The costs of the method to confirm the diagnosis of hypercortisolism was calculated comparing Option A using MSC (UFCx2, low-dose dexamethasone suppression test [LDDST]) that requires patient hospitalization versus Option B using MSVC (UFCx2, LDDST) in which the evaluation is done outside the Hospital. A budget impact analysis for one year was developed, and a sensitivity analysis in different scenarios was performed. Reproducibility and diagnostic performance of MSVC and MSC were also measured. RESULTS Salivary cortisol is a sound analytical method for evaluating free serum cortisol due to its classification accuracy, good imprecision, linearity, and stability. AUC(ROC) comparison between MSVC and MSC shows no significant differences. The substitution of the MSC for MSVC in our hospital could save between €16,762 and €132,804 in one year. CONCLUSIONS The use of MSVC in the diagnosis of hypercortisolism can result in a substantial decrease in the budget impact, without losing diagnosis accuracy and reliability, a significant advantage considering the current emphasis on reducing the financial burden of health care.

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease

OBJECTIVE To assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushings disease (CCS) case. MATERIAL AND METHODS Laboratory tests included morning and midnight serum cortisol levels, 24h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques. RESULTS A patient was referred to our unit with a diagnosis of Cushings syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results. CONCLUSIONS Our case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis.

What are the biochemical parameters of pleural fluid that best identify parapneumonic effusions

To the Editor, In the recent review of the British Thoracic Society guidelines for the investigation of unilateral pleural effusion in adults, 1 there was no mention of biochemical analysis of pleural fluid for the diagnosis of parapneumonic pleural effusions (PPE). PPE is an exudate associated with pneumonia, abscess or bronchiectasis, called empyema when it contains pus. 2 The biochemical analysis of pleural fluid is important for the diagnosis of PPE. The aim of our study was to determine the accuracy of biochemical parameters of pleural fluid for the diagnosis of PPE, using receiveroperating characteristic (ROC) techniques by analysing the area under the ROC curve (AUC) and determining the optimal cut-off value. We studied 207 pleural fluids obtained anaerobically by thoracocentesis using gasometry syringes in 110 men and 97 women aged between 1 and 90 y (average 58 y), from June 2005 to July 2006. The following variables were analysed: protein, glucose, lactate dehydrogenase (LDH), lactate and amylase by INTEGRA 400 (Roche Diagnostics S.L w , Barcelona, Spain), adenosine deaminase (ADA) by Modular P (Roche Diagnostics S.L w ), pH and pCO2 by gasometer IL-1620 (Izasa S.A. w , Barcelona, Spain), and the aetiological diagnosis of pleural effusion discharged from hospital after evaluating clinical and radiological data and laboratory tests. Protein was analysed by Biuret reaction, glucose by enzymatic reference method with hexokinase, LDH, lactate, amylase and ADA by enzymatic colorimetric methods according to the International Federation of Clinical Chemistry. The serum LDH reference range was 135 –225 U/L. The diagnosis of PPE required an acute febrile illness with purulent sputum and pulmonary infiltrates in association with a pleural effusion or positive pleural fluid culture or positive pleural fluid Gram stain or purulent pleural fluid. Pleural fluids were classified into two groups: PPE and non-PPE. Statistical analysis was performed using the software Medcalc w . Forty-six of 207 pleural fluids studied were PPE (14 uncomplicated PPE, eight complicated PPE and 24

Effect of bariatric surgery on microvascular dysfunction associated to metabolic syndrome: a 12-month prospective study

Objective:To prospectively evaluate the effect of weight loss after bariatric surgery on microvascular function in morbidly obese patients with and without metabolic syndrome (MetS).Methods:A cohort of morbidly obese patients with and without MetS was studied before surgery and after 12 months of surgery. Healthy lean controls were also examined. Microvascular function was assessed by postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated from laser-Doppler skin blood flow and blood pressure. Regression analysis was performed to assess the contribution of different clinical, metabolic and biochemical parameters to microvascular function.Results:Before surgery, 62 obese patients, 39 with MetS and 23 without MetS, and 30 lean control subjects were analyzed. The absolute area under the hyperemic curve (AUCH) CVC of PORH was significantly decreased in obese patients compared with lean control subjects. One year after surgery, AUCH CVC significantly increased in patients free of MetS, including patients that had MetS before surgery. In contrast, AUCH CVC did not significantly change in patients in whom MetS persisted after surgery. Stepwise multivariate regression analysis showed that only changes in HDL cholesterol (HDL-C) and oxidized LDL (oxLDL) independently predicted improvement of AUCH after surgery. These two variables together accounted for 40.9% of the variability of change in AUCH CVC after surgery.Conclusions:Bariatric surgery could significantly improve microvascular dysfunction in obese patients, but only in patients free of MetS after surgery. Improvement of microvascular dysfunction is strictly associated to postoperative increase in HDL-C levels and decrease in oxLDL levels.