Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme.

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01-1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

What is the context? Glioblastoma has an impact on the platelet number and the functional state of platelets. Platelets can be activated by tumor cells, and platelets count and function may impact patient survival. It has been showed an association between thrombocytosis and a decreased overall survival, with a small reduction in glioma risk associated with the long-term use of low-dose aspirin.Platelet function before and during the perioperative period in patients with glioblastoma has not been systematically investigated. Limited data suggest that platelet function may be impaired before and throughout the perioperative period, and that impaired platelet function affects clinical outcome.What is new? In this prospective study, we systematically investigated how glioblastoma provokes systemic alterations of hemostasis. We enrolled 60 consecutive patients (sample size calculated) subjected to resection of glioblastoma multiforme, and other 40 consecutive patients undergoing laparoscopic resection of colon cancer, as a comparative group, in order to differentiate hemostasis and coagulation profiles of two tumors (glioblastoma and colon adenocarcinoma) with high prothrombotic power. Forty healthy volunteers were also included to establish local reference values.We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. All these analyses were carried out at baseline (T0, time 0, before surgery) and 2 (T2), 24(T24) and 48-hour (T48) after surgery.We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01­1.06)).What is the impact? This study provides further evidence that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.The cut-offs obtained can potentially to provide risk stratification for clinical outcome and to be hypothesis generating research to be confirmed by RCTs.

Whole Blood Platelet Aggregation Assessed by ROTEM Platelet Equipment in Healthy Volunteers from Southern Europe: A Verification Study.

BACKGROUND: This study aimed to verify the reference intervals (RIs) recently established in the Danish population for platelet aggregation induced by a specific agonist of the rotational thromboelastometry (ROTEM) platelet impedance aggregometer. Our local results were also compared with those published by the manufacturer. METHODS: This prospective study included healthy blood donors. Subjects with a history of coagulopathy, those on antiplatelet/anticoagulant therapy, or those taking nonsteroidal anti-inflammatory drugs were excluded. Blood samples were collected for ROTEM® platelet arachidonic acid thromboelastometry (ARATEM), adenosine-di-phosphate thromboelastometry (ADPTEM), and thrombin receptor-activating peptide-6 thromboelastometry (TRAPTEM). The parameters determined were the area under the curve (AUC, ohm·min), maximum amplitude at 6 min (A6, ohm), and maximum slope (MS, ohm/min). Values are expressed as 2.5th-97.5th percentiles. Comparisons are expressed as local vs Danish and manufacturer population RIs. Number (n) and percentage (%) of local tests below (<2.5th percentile) of the Danish and manufacturer population are shown. RESULTS: Forty donors (19 male; mean, 58 [range: 56 to 60] years) were included. There were no differences between our results and those published for the Danish population. In contrast, all ARATEM and ADPTEM values were lower in the local vs manufacturer group. CONCLUSIONS: Our results confirm those published for the Danish population, with respect to the ROTEM platelet aggregometer. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT02652897.

Tiempo de estancia prolongado en los pacientes ingresados por insuficiencia cardiaca aguda / Length of stay in patients admitted for acute heart failure

Objetivo: Identificar los factores asociados al tiempo de estancia hospitalaria prolongado en pacientes ingresados/as por insuficiencia cardiaca aguda. Método: Estudio observacional de cohorte multipropósito que incluyó pacientes del registro EAHFE (Epidemiology Acute Heart Failure in Emergency) ingresados/as por insuficiencia cardiaca aguda en 25 hospitales españoles. Se recogieron variables demográficas y clínicas, el día y el lugar del ingreso. La variable resultado principal fue el tiempo de estancia hospitalaria mayor que la mediana. Resultados: Se incluyeron 2400 pacientes con una edad media de 79,5 (±9,9) años, de los cuales 1334 (55,6%) eran mujeres. Quinientos noventa (24,6%) ingresaron en la unidad de corta estancia (UCE), 606 (25,2%) en cardiología y 1204 (50,2%) en medicina interna o geriatría. La mediana del tiempo de estancia hospitalaria fue de 7,0 (intervalo intercuartílico: 4-11 días). Cincuenta y ocho (2,4%) pacientes fallecieron y 562 (23,9%) sufrieron un reingreso a los 30 días tras el alta. Los factores independientes asociados a un tiempo de estancia hospitalaria prolongado fueron la enfermedad pulmonar obstructiva crónica, ser portador de un dispositivo, tener un factor precipitante desconocido o no común, la presencia en urgencias de insuficiencia renal, hiponatremia y anemia, no ingresar en una UCE o no disponer de dicha unidad e ingresar un lunes, martes o miércoles; y los asociados a un tiempo de estancia hospitalaria ≤7 días fueron la hipertensión arterial y tener como factor precipitante una crisis hipertensiva o la falta de adherencia al tratamiento. El área bajo la curva del modelo mixto ajustado al centro fue de 0,78 (intervalo de confianza del 95%: 0,76-0,80; p <0,001). Conclusiones: Hay una serie de factores asociados con un tiempo de estancia hospitalaria prolongado que deben ser considerados para la gestión del proceso de la insuficiencia cardiaca aguda (AU)

Objective: To identify the factors associated with prolonged length of hospital stay in patients admitted for acute heart failure. Methods: Multipurpose observational cohort study including patients from the EAHFE registry admitted for acute heart failure in 25 Spanish hospitals. Data were collected on demographic and clinical variables and on the day and place of admission. The primary outcome was length of hospital stay longer than the median. Results: We included 2,400 patients with a mean age of 79.5 (9.9) years; of these, 1,334 (55.6%) were women. Five hundred and ninety (24.6%) were admitted to the short stay unit (SSU), 606 (25.2%) to cardiology, and 1,204 (50.2%) to internal medicine or gerontology. The mean length of hospital stay was 7.0 (RIC 4-11) days. Fifty-eight (2.4%) patients died and 562 (23.9%) were readmitted within 30 days after discharge. The factors associated with prolonged length of hospital stay were chronic pulmonary disease; being a device carrier; having an unknown or uncommon triggering factor; the presence of renal insufficiency, hyponatremia and anaemia in the emergency department; not being admitted to an SSU or the lack of this facility in the hospital; and being admitted on Monday, Tuesday or Wednesday. The factors associated with length of hospital stay≤7days were hypertension, having a hypertensive episode, or a lack of treatment adherence. The area under the curve of the mixed model adjusted to the center was 0.78 (95% CI: 0.76-0.80; p<0.001). Conclusions: A series of factors is associated with prolonged length of hospital stay and should be taken into account in the management of acute heart failure (AU)

Administration of fibrinogen concentrate for refractory bleeding in massively transfused, non-trauma patients with coagulopathy: a retrospective study with comparator group.

BACKGROUND: This retrospective, single centre study was conducted to investigate the efficacy of fibrinogen concentrate (FBNc) in decreasing blood requirements and reaching optimal fibrinogen level, in non-trauma, massively transfused, bleeding patients with coagulopathy. METHODS: Over a 3-years period, all patients for whom a massive transfusion protocol was activated and had received ≥ 4 units of allogeneic blood components within a ≤ 4 h period, were included. Patients were classified according to whether they received FBNc or achieved an optimal fibrinogen level of ≥ 2 g/L within 24 h after FBNc administration. RESULTS: Seventy-one patients received 2 [2,4] g of FBNc (FBNc group) and 72 did not (comparator group). FBNc was administered after transfusing 5 [5,9] blood component units, 3 [2,6] hours after massive transfusion protocol activation. Linear regression analysis showed that SOFA (AOR 0.75 [95% CI:0.08-1.43]) and admission fibrinogen level (AOR -2.7 [95% CI:-4.68 - -0.78]), but not FBNc administration, were independently associated with total transfused units. There was a significant inverse relation between both admission and target fibrinogen levels, and total transfused components. Logistic regression showed a direct relationship between admission fibrinogen level and achieving a target level ≥ 2 g/L (AOR 3.29 [95% CI;1.95-5.56]). No thromboembolic events associated with FBNc were observed. CONCLUSIONS: In massively transfused, non-trauma patients with coagulopathy and refractory bleeding, late administration of low FBNc dosage was not associated with decreased blood transfusion or increased post-infusion fibrinogen level. Given that both fibrinogen upon admission and target fibrinogen levels were associated with decreased blood transfusion, earlier administration and higher doses of FBNc could be needed.

High-throughput operando Raman-quadrupole mass spectrometer (QMS) system to screen catalytic systems.

This paper describes the design and setup of a high-throughput Raman system for an array of eight parallel catalytic reactors during reaction conditions. The "operando" methodology combines in situ spectroscopy during catalytic reaction with a simultaneous activity measurement. The high-throughput operando Raman system, multi-operando, is a device that automates this operando methodology for several catalyst samples at the same time, all samples being in the same reaction conditions. We describe how the system is made, how Raman system positions and acquires spectra, and how each reactor outlet gas is selected and analyzed.

Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study.

The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ±â€Š3 to 1.7 ±â€Š1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ±â€Š1500 to 200 ±â€Š100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.

Mal de Pott i abscés prevertebral i paravertebral en un nen de 23 mesos d’edat / Mal de pott y absceso prevertebral y paravertebral en un niño de 23 meses de edad / Pott disease and pre- and para-vertebral abscesses in a 23-month-old boy

La malaltia tuberculosa és tan antiga com l’espècie humana1 , i encara se’n continuen detectant casos en la població pediàtrica que viu a Catalunya. Sens dubte, l’important flux migratori dels darrers anys és un element amb un pes específic important en aquesta constatació, per bé que no pas l’únic. Es presenta el cas d’un nen de 23 mesos d’origen magribí, nascut a Catalunya, que consulta a Urgències per una coixesa a totes dues cames de set dies d’evolució, sense febre ni antecedent traumàtic. En l’exploració destacava una temperatura axil•lar de 37.5 °C. L’examen físic per aparells no va mostrar alteracions. Tant l’analítica com la punció lumbar realitzades van ser normals. La radiologia de tòrax i de malucs fou anodina i en la de columna dorsolumbar es detectà un pinçament de l’espai D-11/D-12 amb espondilòlisi i espondilolistesi. El PPD fou positiu (25 x 17 mm) i el Ziehl-Nielsen i el cultiu en medi Löwenstein d’aspirats gàstrics seriats i LCR, negatius. La ressonància magnètica nuclear mostrà un abscés prevertebral i paravertebral de D-08 a L-2 amb espondilòlisi i espondilolistesi de D-10 a D-12. Sota l’orientació diagnòstica de tuberculosi vertebral (mal de Pott) i abscés prevertebral i paravertebral s’inicià el tractament amb quatre fàrmacs tuberculostàtics. Amb la punció-aspiració es van obtenir 12 cc de càseum (Ziehl-Nielsen negatiu i Löwenstein positiu) i es col•locà una cotilla d’immobilització externa. Els estudis immunitaris i la serologia a VIH foren negatius i en l’estudi de contactes familiars destacava una pleuropneumònia tuberculosa en el pare, tuberculosi primària en la mare i infecció tuberculosa latent en el germà. L’evolució clínica fou favorable, i l’alta hospitalària s’aconseguí al cap de 32 dies. Als 10 mesos de l’ingrés deambula normalment i ha millorat la cifosi regional i local (AU)

A pesar de ser tan antigua como la especie humana 1 , se continúan detectando casos de enfermedad tuberculosa en la población pediátrica que vive en Catalunya. Sin duda, el importante flujo migratorio de los últimos años es un elemento con un importante peso específico en la causa de esta constatación, si bien no es el único. Se presenta el caso de un niño de 23 meses de origen magrebí, nacido en Catalunya, que consultó a Urgencias por presentar cojera de ambas piernas de siete días de evolución, sin fiebre ni antecedente traumático. En la exploración, destacaba una temperatura axilar de 37.5 °C. El examen físico por aparatos no mostró alteraciones. La analítica y la punción lumbar realizadas fueron normales. La radiología de tórax y caderas fue anodina y en la de columna dorso-lumbar se detectó pinzamiento del espacio D-11/D-12 con espondilolisis y espondilolistesis. El P.P.D. fue positivo (25 x 17 mm) y el Zhiel-Nielsen y el Löwenstein de aspirados gástricos seriados y LCR negativos. La resonancia magnética nuclear mostró un absceso prevertebral y paravertebral de D-08 a L-2 con espondilolisis y espondilolistesis de D-10 a D-12. Bajo la orientación diagnóstica de tuberculosis vertebral (mal de Pott) y absceso prevertebral y paravertebral, se inició tratamiento con cuatro fármacos según pauta. En la punción-aspiración se obtuvieron 12 cc de cáseum (Zhiel-Nielsen negativo y Löwenstein positivo) y se procedió a colocar corsé de inmovilización externo. Los estudios inmunitarios y la serología a VIH fueron negativos y en el estudio de contactos familiares destacó el hallazgo de una pleuroneumonía tuberculosa en el padre, tuberculosis primaria en la madre e infección tuberculosa en el hermano. La evolución clínica fue favorable, y recibió el alta del hospital a los 32 días. A los 10 meses del ingreso deambula normalmente con mejora evidente de la cifosis regional y local (AU)

Despite being described to be as old as humankind, pediatric cases of tuberculosis continue to be diagnosed in Catalonia. Many factors contribute to the persistence of this problem, including the increase in migratory flow documented in recent years. We present the case of a 23 month-old child of Maghribian descent, who presented with a 7-day history of progressive limpness. There was no recent history of trauma, and the child was afebrile. On physical examination, axillary temperature was 37.5o C, and examination by systems and organs was normal. Laboratory evaluation, including CSF, was normal. Chest and hips XRays were normal, but imaging of the thoracolumbar spine disclosed narrowing of the T11-T12 intervertebral space, with spondylolysis and spondylolystesis. PPD was positive (25 x 17 mm) and the Ziehl-Nielsen and Löwenstein stains of serial gastric aspirates and CSF were negative. MRI showed a pre- and para-vertebral abscess extending from T-8 through L-2, with spondylolysis and spondylolystesis of T-10 through T-12. A needle aspiration with drainage of 12 mL of caseum was performed. The material was negative for Ziehl-Nielsen and positive for Löwenstein stains. With the clinical diagnosis of vertebral tuberculosis (Pott disease) and prevertebral and paravertebral abscess, the patient was started with a 4-drug regimen, and was fitted for a trunk brace. Immune function studies were normal and HIV serology was negative, and contact evaluation revealed a tuberculous pleuropneumonia in the father, primary tuberculosis in the mother, and primary infection in the brother. Clinical course was favorable, and the patient was discharged from the inpatient unit after 32 days. Follow-up at 10 months from diagnosis shows normal walking and improvement in the regional and local kyphosis (AU)