Uso de los test viscoelásticos en los principales escenarios clínicos de sangrado en los centros españoles / Use of viscoelastic tests in the principle bleeding scenarios in Spanish hospitals

Los test viscoelásticos son tecnologías diseñadas para estudiar la dinámica de formación del coágulo, identificar coagulopatías en tiempo real, realizar un diagnóstico y guiar el tratamiento hemostático de forma específica. Sus principales aplicaciones son el tratamiento de la hemorragia significativa en cualquier escenario, así como el de otras situaciones que cursen con alteraciones clínicamente relevantes de la hemostasia, como la coagulopatía del paciente crítico. Su uso se establece mediante algoritmos basados en la evidencia científica que están sujetos a variabilidad en función del contexto clínico. Basada en una encuesta distribuida en varios hospitales, esta revisión objetiva el grado de extensión y la homogeneidad en el uso de los test viscoelásticos en nuestro medio en cirugía cardiaca, en el trasplante hepático y en el paciente politraumatizado. Los resultados obtenidos revelan disparidad en aspectos clave que van desde su capacidad diagnóstica propiamente dicha hasta la interpretación de los parámetros básicos. Estos hallazgos permiten plantear potenciales áreas de investigación con el objetivo de mejorar su rendimiento.(AU)

Viscoelastic tests are designed to study the dynamics of clot formation, identify coagulopathies in real time, arrive at a diagnosis, and guide patient-specific administration of haemostatics. They are mainly used to treat clinically significant bleeding in any setting, and are also used in other situations involving clinically relevant alterations in haemostasis, such as coagulopathy in critically ill patients. These tests are administered following evidence-based algorithms that vary depending on the clinical context. This review summarises the results of a survey conducted in several hospitals to determine the prevalence and standardisation of viscoelastic tests in cardiac surgery, liver transplantation, and multiple trauma patients in Spain. The results reveal divergent opinions on key aspects, ranging from the diagnostic capacity of these tests to the interpretation of the basic parameters. On the basis of these findings, we propose a number of potential areas in which further research will improve the performance of these tests.(AU)

Use of viscoelastic tests in the principle bleeding scenarios in Spanish hospitals.

Viscoelastic tests are designed to study the dynamics of clot formation, identify coagulopathies in real time, arrive at a diagnosis, and guide patient-specific administration of haemostatics. They are mainly used to treat clinically significant bleeding in any setting, and are also used in other situations involving clinically relevant alterations in haemostasis, such as coagulopathy in critically ill patients. These tests are administered following evidence-based algorithms that vary depending on the clinical context. This review summarises the results of a survey conducted in several hospitals to determine the prevalence and standardisation of viscoelastic tests in cardiac surgery, liver transplantation, and multiple trauma patients in Spain. The results reveal divergent opinions on key aspects, ranging from the diagnostic capacity of these tests to the interpretation of the basic parameters. On the basis of these findings, we propose a number of potential areas in which further research will improve the performance of these tests.

Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.

INTRODUCTION: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. METHODS: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. RESULTS: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (p = .819 and p = .265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. CONCLUSION: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

[Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study]. / Eficacia de la tromboprofilaxis con heparina de bajo peso molecular en pacientes críticos con COVID-19: estudio observacional, prospectivo y multicéntrico.

Introduction: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. Metohds: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. Results: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (P=.819 and P=.265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. Conclusion: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

Clinical characterization of gingival type of burning mouth syndrome: a cross-sectional study.

BACKGROUND: The aim of this study is to investigate the prevalence of localized intraoral neuropathic pain in a cluster of patients who reported the involvement of gingival site as only clinical manifestation of dysesthesia, analysing type and distribution of symptoms. MATERIAL AND METHODS: Burning mouth syndrome (BMS) patients were enrolled in the study. Patients were screened through laboratory test and a conventional oral examination with periodontal chart. A questionnaire to collect data on symptoms, oral site involved, quality of sleep, anxiety was submitted to all the patients. RESULTS: A total of 236 patients were recruited. Seventy-six patients (32.2%) presented generalized type, whereas 160 (67.8%) had localized type. In the localized BMS group, the gingiva was involved in 70 patients and in 33 of these it was the only site involved. In the gingival subgroup, 35 patients reported burning, 29 pain and 24 xerostomia. CONCLUSIONS: To best our knowledge, this study is the first that analyses gingival involvement as the only site in BMS and it could encourage further investigations to understand the etiopathogenesis of gingival BMS.

High D dimers and low global fibrinolysis coexist in COVID19 patients: what is going on in there?

BACKGROUD: COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054-62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test. METHODS: Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection. RESULTS: Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 109/L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score. CONCLUSION: In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.

Treatment of a peri-implantitis defect using a mini-invasive surgical approach (MISA) and deproteinized bovine bone mineral with 10% collagen: a case series.

This pilot study evaluates the effectiveness of the Mini-Invasive Surgical Approach (MISA) in the treatment of peri-implantitis defect. MISA is based on the use of the deproteinized bovine bone mineral with 10% collagen in combination with a minimal flap. The main principle is the elevation of a flap to access to the peri-implantitis defect only on one side (palatal aspect), leaving the opposite site intact. The study was designed as a non-controlled, non-randomized pilot study. In 10 consecutive subjects, 10 implants with diagnosis of perimplantitis were selected. In all the treated sites, primary closure was obtained at completion of the surgical procedure. No relevant pain, edema and hematoma were noted. The reported surgical approach resulted in significant clinical and radiographic improvements while limiting patient morbidity. After 1-year follow-up minimal mucosal recession, probing depth reduction and radiographic bone gain were noted.

Thermafil: A New Clinical Approach Due to New Dimensional Evaluations.

BACKGROUND: There are a lot of techniques to obturate the root canals, but lateral condensation of gutta-percha is the most used one. An important aspect of thermafil is the error margin tolerated by the manufacturer in the production of plastic carriers. In literature, there is no evidence about discrepancy percentage between different carriers. It is demonstrated that the error margin of gutta-percha is 0.5% and is 0.2% for metal files (ISO standards). OBJECTIVE: The aim of this study was to evaluate the real dimensions of thermafil plastic carriers observed by the stereo microscope measuring the dimensional discrepancy between them. METHODS: For this study, 80 new thermafil (Dentsply Maillefer) have been selected. 40 thermafil 0.25 and 40 thermafil 0.30. Through 60X stereo microscope, the dimensions of the plastic carrier tips have been measured. The dimensions of the plastic carrier were also measured after a heating cycle. ZL GAL 11TUSM (Zetaline stereo evolution) microscope was used to observe the samples. Measurements were made through a dedicated software (Image Focus). All samples were analysed at 60X. RESULTS: A non-parametric paired test (Wilcoxon test) was used to compare baseline and after heating values; p-values ≤ 0.05 were assumed to be statistically significant. CONCLUSION: The samples we measured showed a mean value of the diameters in Thermafil 25 that was 0.27 mm, for Thermafil 30 the mean value was 0.33 mm.We have measured a dimensional variable of 8% in the 25 group while in group 30 the maximum possible variation found was 4%, that's why we propose a new protocol of obturation with thermafil. We can also conclude that a single heating process does not affect clinically the plastic carrier dimensions.

Perfusión aislada de extremidad inferior con fuga de quimioterapéutico / Isolated limb perfusion with cytostatic drug leakage

La perfusión aislada de la extremidad es el tratamiento del melanoma en estadio iii, con metástasis en tránsito. Esta técnica permite la administración de citostáticos a concentración y temperatura eficaces, que no podrían ser administrados de manera sistémica debido a su toxicidad. La toxicidad debido al paso a la circulación sistémica de quimioterápico procedente de la extremidad es la complicación más grave a corto plazo, y se manifiesta mediante el síndrome de respuesta inflamatoria sistémica en el postoperatorio inmediato. La detección precoz de esta complicación y su manejo perioperatorio requiere un abordaje multidiscilplicar, en el que el anestesiólogo tiene un papel clave. Presentamos un caso de perfusión aislada de la extremidad inferior en el que el procedimiento tuvo que ser interrumpido por paso de factor de necrosis tumoral a la circulación sistémica, con grave repercusión hemodinámica intraoperatoria (AU)

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions (AU)

Isolated limb perfusion with cytostatic drug leakage. / Perfusión aislada de extremidad inferior con fuga de quimioterapéutico.

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions.

Cortical responses before 6 months of life associate with later autism.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

Manejo perioperatorio en el trasplante hepático en los centros españoles: resultados de una encuesta / Perioperative management of liver transplantation in Spanish hospitals: results of a survey

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Are the school prevention programmes - aimed at de-normalizing smoking among youths - beneficial in the long term? An example from the Smoke Free Class Competition in Italy.

Tobacco smoking by young people is of great concern because it usually leads to regular smoking, nicotine addiction and quitting difficulties. Young people "hooked" by tobacco maintain the profits of the tobacco industry by replacing smokers who quit or die. If new generations could be tobacco-free, as supported by tobacco endgame strategies, the tobacco epidemic could end within decades. Smoking prevention programmes for teens are offered by schools with the aim to prevent or delay smoking onset. Among these, the Smoke Free Class Competition (SFC) was widely implemented in Europe. Its effectiveness yielded conflicting results, but it was only evaluated at short/medium term (6 - 18 months). The aim of this study is to evaluate its effectiveness after a longer follow-up (3 to 5 years) in order to allow enough time for the maturing of the students and the internalization of the experience and its contents. Fifteen classes were randomly sampled from two Italian high schools of Bologna province that regularly offered the SFC to first year students; 382 students (174 participating in the SFC and 208 controls) were retrospectively followed-up and provided their "smoking histories". At the end of their last year of school (after 5 years from the SFC), the percentage of students who stated that they were regular smokers was lower among the SFC students than in controls: 13.5% vs 32.9% (p=0.03). From the students' "smoking histories", statistically significant protective ORs were observed for SFC students at the end of 1st and 5th year: 0.42 (95% CI 0.19-0.93) and 0.32 (95% CI 0.11-0.91) respectively. Absence of smokers in the family was also a strongly statistically significant factor associated with being a non-smoker student. These results suggest that SFC may have a positive impact on lowering the prevalence of smoking in the long term (5 years).

Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment.

BACKGROUND: Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT. METHODS: A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included. RESULTS: The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1·3679 + 0·05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0·387 [0·340 to 0·432]) and moderate for the preperfusion period (LLC [95% CI]: 0·789 [0·747 to 0·824]), but very poor for the postreperfusion period (LLC [95% CI] 0·170 [0·105 to 0·233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0·788 [0·745-0·832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2·08 [1·30-3·33], P = 0·002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion. CONCLUSION: FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration.

Cortical specialisation to social stimuli from the first days to the second year of life: A rural Gambian cohort.

Brain and nervous system development in human infants during the first 1000days (conception to two years of age) is critical, and compromised development during this time (such as from under nutrition or poverty) can have life-long effects on physical growth and cognitive function. Cortical mapping of cognitive function during infancy is poorly understood in resource-poor settings due to the lack of transportable and low-cost neuroimaging methods. Having established a signature cortical response to social versus non-social visual and auditory stimuli in infants from 4 to 6 months of age in the UK, here we apply this functional Near Infrared Spectroscopy (fNIRS) paradigm to investigate social responses in infants from the first postnatal days to the second year of life in two contrasting environments: rural Gambian and urban UK. Results reveal robust, localized, socially selective brain responses from 9 to 24 months of life to both the visual and auditory stimuli. In contrast at 0-2 months of age infants exhibit non-social auditory selectivity, an effect that persists until 4-8 months when we observe a transition to greater social stimulus selectivity. These findings reveal a robust developmental curve of cortical specialisation over the first two years of life.

Rotation thromboelastometry velocity curve predicts blood loss during liver transplantation.

BACKGROUND: Patients undergoing liver transplantation (LT) have a high risk of bleeding. The goal of this study was to assess whether the first derivative of the velocity waveform (V-curve) generated by whole blood rotation thromboelastometry (ROTEM®) can predict blood loss during LT. METHODS: Preoperative V-curve parameters were retrospectively evaluated in 198 patients. Patients were divided into quartiles based on blood loss: low (LBL) in the first quartile and high (HBL) in the higher quartiles. A subgroup analysis was performed with patients stratified according to cirrhosis aetiology. A logistic regression model and receiver operator characteristics (ROC) curve were used to test the capacity of the V-curve, to discriminate between LBL and HBL. RESULTS: In the HBL group, the V-curve showed a lower maximum velocity of clot generation (MaxVel), a lower area under maximum velocity curve (AUC), and a higher time-to-maximum velocity (t-MaxVel) than in the LBL group. t-MaxVel was the only parameter showing a capacity to discriminate between the two groups, with a ROC area of 0.69 (95% CI; 0.62-0.74). The ROC area was 0.78 (95% CI; 0.75-0.83) for the 148 patients with cirrhosis, 0.73 (0.60-0.82) for patients with viral hepatitis and 0.83 (0.78-0.96) for patients with alcoholic hepatitis, the group that showed the best discriminative capacity. Moderate but significant correlations were found between all parameters of V-curve and BL. CONCLUSIONS: Pre-transplant V-curve obtained from ROTEM is a promising tool for predicting BL risk during LT, particularly in patients with cirrhosis.

Intraoperative Management of High-Risk Liver Transplant Recipients: Concerns and Challenges.

Liver transplantation (LT) offers patients with liver disease a real chance for long-term survival. In the past decade, successful survival after LT along with the Model for End-Stage Liver Disease-based allocation policy have increased willingness to accept patients with a higher risk profile and marginal organs and to prioritize the sickest patients on the waiting list. Therefore, the anesthesiologist now deals with very challenging patients. In the present review, we aimed to highlight key aspects of intraoperative LT management in high-risk patients and to place these aspects in the perspective of their impact on perioperative outcomes. Conservative standardized perioperative strategies mandate a switch toward accurate and tailored perioperative anesthetic care to maintain the steady improvement in recipient survival rates after LT. In our opinion, continuous assessment of fluid status and cardiac performance, strategies promoting graft decongestion, rational hemostatic management, and the identification of LT recipients with potential risk of vascular complications should constitute the cornerstone of intraoperative management.

Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements.