Effectiveness and Safety of CT-P13 (Biosimilar Infliximab) in Patients with Inflammatory Bowel Disease in Real Life at 6 Months.

BACKGROUND: CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. AIMS: To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. METHODS: This is a prospective observational study in patients with moderate to severe Crohn's disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. RESULTS: 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. CONCLUSIONS: CT-P13 was efficacious and well tolerated in patients with CD or UC.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Acute predictors for mortality after severe TBI in Spain: Gender differences and clinical data.

OBJECTIVE: The main objective of this study is to determine whether gender affects global mortality and functional outcome after severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included 629 patients with severe TBI (14.9% female) admitted to the ICU of a university hospital. Patients were split into gender groups to study potential differences in global mortality and functional outcome at ICU discharge and 6 months post-trauma using the GOS. The following variables were analysed: age, intracranial injury, injury mechanism, injury severity, factors contributing to secondary brain injury, monitoring level, treatment, complications, length of stay in the ICU and cause of death. RESULTS: No differences were found between gender groups in neuromonitoring level or surgical procedures. Women had higher APACHE II scores, a higher incidence of pre-hospital hypotension, anaemia and transfusion and higher mortality rates in the ICU (OR = 1.74; 95% CI = 1.09-2.77) and 6 months post-trauma (OR = 1.65; 95% CI = 1.02-2.67). There were no significant differences in functional outcome at ICU discharge or 6 months post-injury. The multivariate analysis did not show gender as an independent predictive factor in mortality after severe TBI. CONCLUSION: In this study, gender was not found to be an independent predictor for poorer outcome after severe TBI.

Predictors of mortality and poor functional outcome in severe spontaneous intracerebral hemorrhage: a prospective observational study.

OBJECTIVE: To analyze mortality and functional outcome in patients with severe spontaneous intracerebral hemorrhage (ICH), and identify the clinical characteristics, radiological findings and therapeutic procedures predictive of mortality in the Intensive Care Unit (ICU) and during hospitalization, as well as of poor functional results at 6 months. DESIGN: A prospective, observational study was carried out. SETTING: Neurocritical Care Unit of a university hospital. PATIENTS: Patients diagnosed with ICH were included over a period of 23 months. VARIABLES OF INTEREST: Demographic characteristics, cardiovascular risk factors, regular medication, laboratory test parameters, cranial CT findings, therapeutic procedures and outcome data. INTERVENTION: None. RESULTS: A total of 186 patients with ICH met the inclusion criteria. Surgery to evacuate ICH was performed in 25.8% of the patients. The mortality rate was 46.7%. The modified Rankin score at 6 months was 5 (RI: 4.6). Multivariate Cox regression analysis showed the presence of diabetes, prior anticoagulation, as well as APACHE II severity and the type of bleeding on the cranial CT scan to be predictors of mortality and poor functional outcomes. On the other hand, neurosurgical procedures and intracranial pressure (ICP) monitoring were associated with better outcomes. CONCLUSION: The presence of comorbidities such as diabetes, or previous anticoagulation, as well as the CT findings were associated to poorer outcomes. In contrast, ICP monitoring and early neurosurgery were predictive of longer survival and better functional outcomes.

[An experimental model of mass-type brain damage in the rat: expression of brain damage based on neurospecific enolase and protein S100B]. / 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.

Accuracy of the S100ß protein as a marker of brain damage in traumatic brain injury.

INTRODUCTION: This study tested the hypothesis that S100ß is a useful screening tool for detecting intracranial lesion (IL) in patients with a normal level of consciousness after traumatic brain injury (TBI). METHODS: One hundred and forty-three post-TBI patients without a decrease in consciousness (GCS = 15) and with at least one neurological symptom (e.g. transitory loss of consciousness, amnesia, headache, dizziness or vomiting) were prospectively included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was obtained within 24 hours post-injury. Diagnostic properties of S100ß for IL prediction in CT scan findings were tested using ROC-analysis. RESULTS: A total of 15 patients (10.5%) had IL. Serum levels were significantly higher in these patients. Significant differences were found between S100ß levels and CT scan findings (p = 0.007). ROC-analysis showed that S100ß is a useful tool for detecting the presence of IL in CT scans (p = 0.007). In this series, the best cut-off for S100ß is 0.130 µg L(-1), with 100% sensitivity and 32.81% specificity. CONCLUSION: Within the first 6 hours post-TBI, serum S100ß seems to be an effective biochemical indicator of IL in patients without a decrease in consciousness. These results indicate that higher S100ß cut-off values substantially improve the clinical relevance of this protein.

Perioperative analgesia by erector spinae plane block in left ventricular assist implant.

In recent years, left ventricular assist devices have become an important element in the management of left ventricular failure refractory to pharmacological treatment. Their implantation (performed by left thoracotomy or sternotomy) generates significant perioperative pain, which can be managed with locoregional anaesthesia techniques. However, opinions vary on their use in cardiac surgery due to interference with the anticoagulant therapy required in these patients. The erector spinae plane block is an alternative to classic locoregional techniques. It does not produce hemodynamic alterations and does not interfere with antiplatelet and anticoagulant therapy, and is therefore an alternative to be considered in cardiac surgery. We present a case of left ventricular assist device implantation under this block prior to the surgical procedure and postoperative infusion through a catheter, obtaining satisfactory results in the management of perioperative pain.

Usefulness of optic nerve ultrasound to predict clinical progression in multiple sclerosis. / Utilidad de la ecografía de nervio óptico como predictor de progresión en esclerosis múltiple.

INTRODUCTION: Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. MATERIAL AND METHODS: We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the 'as low as reasonably achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. RESULTS: Disease progression was significantly correlated with ultrasound findings (P=.041 for the right eye and P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P=.07 for the right eye and P=.043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. DISCUSSION: Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS).

[Predictive models of gestational diabetes, a new prediction mode]. / Modelos predictivos de diabetes gestacional, un nuevo modelo de predicción.

OBJECTIVES: Recognized the value of gestational diabetes (GD) as a health problem, our aim in this work has been to analyze the diagnostic performance of the different today's existing criteria (GEDE, O'Sullivan and Carpenter) after the overload of 100 g of glucose and revise how to increase its efficiency. MATERIALS AND METHODS: We carried out a description of all the variables. In the analytical phase of the work, we used Pearson's Chi square to see if there were differences in the percentage of cases collected in each health center and the proportions contrast test to study the differences between the experimental prevalence. We completed binary logistic regression models using as result variable having or not having gestational diabetes (yes/no) and as predictors the four measurements of the curve with 100 g of glucose overload. To decide which model was better, the stepwise backward-forward analysis and the surface of the ROC curve generated by each of them were considered. RESULTS: We obtained a sample of 170 pregnant women from six different Primary Care Area of Seville health centers who had shown a positive O'Sullivan test with a median age of 35 years. There were significant differences in the prevalence proportions according to the criteria used: GEDE/O'Sullivan p < 0.001; GEDE/Carpenter p < 0.001. Logistic models with three and four predictor variables were equal in discriminatory diagnostic capacity when the GEDE criteria were used (area under the ROC curve = 0.96, 95% CI: 0.93-0.98). The back-forward stepwise analysis stayed with the three-variable model as the most parsimonious. The same did not occur when applying the other two criteria. CONCLUSIONS: Regarding an observational design, we state that there are significant differences in the prevalence proportions observed according to the criteria applied (p < 0.001) and we can also support that using the GEDE criteria, the taking of the third hour could be dispensed with, based on Bayesian criteria and the application of the ROC curve analysis.

Short-term Results From a Training Program to Improve Organ Donation in Uncontrolled Donation After Circulatory Death.

BACKGROUND: In all organ transplantation programs, election of the proper protocol relies primarily on the professionals involved in the detection of potential donors. The objective of our study was to assess the impact of a series of prehospital training sessions, as well as to develop several positive feedback strategies within the uncontrolled organ donation after circulatory death (uDCD) program in our city. METHODS: A before-after intervention study was carried out in 3 steps. First, professionals enrolled in the Emergency Health Services Agency-061 (EPES-061) program underwent specific training to identify potential donors. Second, a specific logotype was designed to alert emergency health care professionals that in cases where cardiopulmonary resuscitation was ineffective and after treatment of all potentially reversible causes, the "chain of survival" should be considered a "chain of opportunities." Third, a positive feedback strategy was put in place, whereby each time a donation was procured, the EPES-061 personnel that had identified the potential donor were notified by phone and in a personal letter. RESULTS: The mean age for donors was 50.5 years of age (interquartile range 37-52.5), and 89.5% of all donations came from male subjects. Positive feedback letters and phone calls, including information on final outcome, were provided to the appropriate personnel in 100% of the cases. Postintervention information showed an increase in both eligible and utilized donors. CONCLUSIONS: Interventions outside the hospital setting that facilitate optimal implementation of the uDCD program are an essential part of this strategy to increase the donor pool and make the wait shorter for transplant patients.

[APACHE II and SAPS II as predictors of brain death development in neurocritical care patients]. / APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.

AIM: To assess the prognostic value of APACHE II and SAPS II scales to predict brain death evolution of neurocritical care patients. PATIENTS AND METHODS: Retrospective observational study performed in a tertiary hospital. Include 508 patients over 16 years old, hospitalized in ICU for at least 24 hours. The variables of interest were: demographic data, risk factors, APACHE II, SAPS II and outcome. RESULTS: Median age: 41 years old (IR: 25-57). Males: 76.2%. Most frequent reason for admission: trauma (55.3%). Medians: Glasgow Coma Scale (GCS), 10 points; APACHE II, 13 points; SAPS II, 31 points; and ICU stay, 5 days. Mortality in the ICU was 28.5% (n = 145) of whom 44 (8.7%) evolved to brain death. Univariate logistic regression analysis showed that GCS, APACHE II and SAPS II scores, as well as ICU stay days behaved as predictors of brain death evolution. However, the multivariate analysis performed including APACHE II and SAPS II scores showed that only APACHE II maintained statistical significance, despite the good discrimination of both scores. CONCLUSION: Transplant coordinators might use the APACHE II score as a tool to detect patients at risk of progression to brain death, minimizing the loss of potential donors.

TITLE: APACHE II y SAPS II como predictores de evolucion a muerte encefalica en pacientes neurocriticos.Objetivo. Evaluar si las escalas pronosticas APACHE II (Acute Physiology and Chronic Health Evaluation II) y SAPS II (Simplified Acute Physiology Score II) son capaces de predecir la evolucion a muerte encefalica en pacientes neurocriticos. Pacientes y metodos. Estudio retrospectivo, observacional, realizado en un hospital de tercer nivel. Se incluyo a 508 pacientes mayores de 16 años, ingresados con patologia neurocritica aguda, con estancia en la unidad de cuidados intensivos de al menos 24 horas. Las variables de interes fueron: datos demograficos, factores de riesgo, APACHE II, SAPS II y resultado pronostico. Resultados. Mediana de edad: 41 años (rango intercuartilico: 25-57). Varones: 76,2%. Motivo de ingreso mas frecuente: traumatismo (55,3%). Medianas: escala de coma de Glasgow (GCS), 10 puntos; APACHE II, 13 puntos; SAPS II, 31 puntos; y estancia en cuidados intensivos, cinco dias. La mortalidad en la unidad de cuidados intensivos fue de 145 (28,5%). De ellos, 44 (8,7%) evolucionaron a muerte encefalica. El analisis de regresion logistica univariante mostro que la GCS, las escalas APACHE II y SAPS II, y los dias de estancia en la unidad de cuidados intensivos se comportaron como variables predictoras de evolucion a muerte encefalica. Sin embargo, en el analisis multivariante realizado con APACHE II y SAPS II, se evidencio que solo APACHE II mantiene significacion estadistica, a pesar de la buena discriminacion de ambas escalas. Conclusion. Los coordinadores de trasplantes podrian usar la escala APACHE II como una herramienta para detectar pacientes con riesgo de evolucion a muerte encefalica, minimizando la perdida de potenciales donantes.

Multiple sclerosis and alcohol use disorders: In-hospital mortality, extended hospital stays, and overexpenditures. / Esclerosis múltiple y trastornos asociados al consumo de alcohol: mortalidad atribuible, prolongación de estancias y exceso de costes hospitalarios.

INTRODUCTION: The objective of this study was to analyse the impact of alcohol use disorders (AUD) in patients with multiple sclerosis (MS) in terms of in-hospital mortality, extended hospital stays, and overexpenditures. METHODS: We conducted a retrospective observational study in a sample of MS patients obtained from minimal basic data sets from 87 Spanish hospitals recorded between 2008 and 2010. Mortality, length of hospital stays, and overexpenditures attributable to AUD were calculated. We used a multivariate analysis of covariance to control for such variables as age and sex, type of hospital, type of admission, other addictions, and comorbidities. RESULTS: The 10,249 patients admitted for MS and aged 18-74 years included 215 patients with AUD. Patients with both MS and AUD were predominantly male, with more emergency admissions, a higher prevalence of tobacco or substance use disorders, and higher scores on the Charlson comorbidity index. Patients with MS and AUD had a very high in-hospital mortality rate (94.1%) and unusually lengthy stays (2.4 days), and they generated overexpenditures (1,116.9euros per patient). CONCLUSIONS: According to the results of this study, AUD in patients with MS results in significant increases in-hospital mortality and the length of the hospital stay and results in overexpenditures.

Severe Supratentorial Intracerebral Hemorrhage: Factors Related to Brain Death Development.

OBJECTIVE: This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). METHODS: A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score ≤ 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. RESULTS: A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P = .003), anticoagulant therapy (OR, 3.561; P = .050), presence of photomotor impairment at admission (OR, 7.095; P = .001), rebleeding after supratentorial ICH (OR, 5.613; P = .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P = .001). CONCLUSIONS: Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors.

Serologic behavior of S100B protein in patients who are brain dead: preliminary results.

OBJECTIVE: The objective of this study is to assess the S100B protein serum concentrations from brain dead (BD) donors to understand whether its level could provide clinical information during BD diagnosis as a potential confirmatory test. METHODS: During 12 months, 26 patients declared BD were prospectively included in this study. Once the diagnosis of BD was achieved, serum S100B protein levels were measured using an electrochemiluminescence assay. For analytical purposes, we selected the maximum S100B serum value reached during the first 5 days of evolution from a historical cohort of 124 survived patients after a severe brain injury (SBI), as well as from 18 healthy donors (HD) and a subgroup of patients who had severe traumatic brain injuries (TBIs) without extracranial injuries. RESULTS: Mean age was 53.48 years (SD, 18.91 years). The BD group had significantly higher S100B serum levels (1.44 µg/L; interquartile ratio [IR], 0.63-3.68) than the SBI (0.34 µg/L; IR, 0.21-0.60) and HD groups (0.06 µg/L; IR, 0.03-0.07; P < .001). Analysis of S100B levels depending on the main cause responsible for BD development showed significant differences between subgroups (P = .012). S100B serum levels were higher in the isolated TBI BD group (P = .004). The S100B value showed an odds ratio for BD diagnosis of 8.38 (95% confidence interval [CI], 1.16-60.45; P = .035). Reciever operating characteristic analysis revealed an area under the curve of 0.92 (95% CI, 0.79-1.00; P = .007). We set a cut-off value of 2 µg/L in S100B serum concentrations. At this level, the diagnostic properties of S100B would reach 100% of specificity and positive predictive value (PPV), and sensitivity and negative predictive value (NPV) of 60% and 86.7%, respectively. CONCLUSION: This preliminary analysis shows for the very first time that BD is associated with higher S100B serum levels, compared with other neurocritical care patients. We also found that the cause of BD development must be considered. Specifically, S100B serum levels in severe isolated TBI patients-with clinical exploration compatible with BD-could be used in a future as confirmatory test.

Clinical variables and neuromonitoring information (intracranial pressure and brain tissue oxygenation) as predictors of brain-death development after severe traumatic brain injury.

BACKGROUND AND PURPOSE: The aim of this study was to ascertain the role of clinical variables and neuromonitoring data as predictors of brain death (BD) after severe traumatic brain injury (TBI). PATIENTS AND METHODS: This prospective observational study involved severe TBI patients admitted to the intensive care unit between October 2009 and May 2011. The following variables were recorded: gender, age, reference Glasgow Coma Scale after resuscitation, pupillary reactivity, prehospital hypotension and desaturation, injury severity score, computed tomography (CT) findings, intracranial hypertension, and low brain tissue oxygenation (Pti02) levels (<16 mm Hg), as well as the final result of BD. RESULTS: Among 61 patients (86.9% males) who met the inclusion criteria, the average age was 37.69 ± 16.44 years. Traffic accidents were the main cause of TBI (62.3%). The patients at risk of progressing to BD (14.8% of the entire cohort) were those with a mass lesion on CT (odds ratio [OR] 33.6; 95% confidence interval [CI]: 3.75-300.30; P = .002), altered pupillary reaction at admission (OR 25.5; 95% CI: 2.27-285.65; P = .009), as well low Pti02 levels on admission (OR 20.41; 95% CI: 3.52-118.33; P < .001) and during the first 24 hours of neuromonitoring (OR 20; 95% CI: 2.90-137.83; P < .001). Multivariate logistic regression showed that a low Pti02 level on admission was the best independent predictor for BD (OR 20.41; 95% CI: 3.53-118.33; P = .001). CONCLUSIONS: Clinical variables and neuromonitoring information may identify TBI patients at risk of deterioration to BD.