Current landscape and support for practical initiation of oncological prehabilitation translatable to thyroid cancer: A position paper.

Despite a growing body of evidence for the effectiveness of prehabilitation, the uptake of prehabilitation in Europe remains low. Contributing factors range from limited awareness and understanding of prehabilitation to a lack of supporting infrastructure and reimbursement challenges. In this position paper, the authors propose a new comprehensive definition of prehabilitation and identify differentiated thyroid cancer as a type of cancer particularly well-suited for prehabilitation. To support clinicians with the implementation of prehabilitation programs in their clinics, the authors discuss the following practical solutions: a) find the most appropriate prehabilitation program for each patient; b) raise awareness among peers; c) develop evidence to demonstrate the effectiveness of prehabilitation; d) expand the interdisciplinary team; e) expand your network and make use of existing assets; f) utilize learnings from the COVID-19 pandemic.

Serological autoimmune profile of systemic lupus erythematosus in deep and non-deep endometriosis patients.

OBJECTIVE: Several studies have reported a high prevalence of autoimmune diseases such as systemic lupus erythematosus (SLE) in endometriosis patients. The aim of this study was to evaluate the SLE autoimmune antibody profile in patients with deep (DE) and non-deep endometriosis (Non-DE). MATERIALS AND METHODS: Four groups of premenopausal patients were evaluated: patients with DE (n = 50); patients with ovarian endometriomas (Non-DE; n = 50); healthy patients without endometriosis (C group; n = 45); and SLE patients without endometriosis (SLE group; N = 46). Blood samples were obtained and the standard SLE autoimmune profile was evaluated in all patients. Pain symptoms related to endometriosis and clinical SLE manifestations were also recorded. RESULTS: The DE group presented a statistically significant higher proportion of patients with antinuclear antibodies (ANA) (20%) compared to the Non-DE group (4%) and C group (2.2%). Levels of complement were more frequently lower among DE and Non-DE patients although differences did not reach statistical significance. Similarly, anti-dsDNA antibodies and anticoagulant lupus were positive in more patients of the DE group but did not reach statistical significance. The DE group complained of more arthralgia and asthenia compared to the Non-DE and C groups. CONCLUSIONS: The results of this study showed higher positivity of ANA and greater arthralgia and asthenia in patients with DE compared with Non-DE patients and healthy controls, suggesting that they may have a higher susceptibility to autoimmune diseases and present more generalized pain.

Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients / Estrategias de anticoagulación y riesgo de sangrado en pacientes ingresados en una Unidad de Cuidados Intensivos por COVID-19

Objective To evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients. Design Retrospective observational and analytical cohort study. Setting COVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020. Patients 201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic. Interventions The incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen. Main variables of interest VTE, bleeding and mortality. Results 78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p<0.001 and p<0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26–4.58, p=0.008) but had no impact on VTE. Conclusion Intermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients (AU)

Objetivo Evaluar la incidencia de eventos trombóticos, sangrado y mortalidad comparando diferentes regímenes de anticoagulación en pacientes ingresados en unidades de Cuidados Intensivos (UCI) por COVID-19. Diseño Estudio de cohortes retrospectivo observacional y analítico. Ámbito Pacientes con COVID-19 ingresados en una UCI de un hospital terciario entre marzo y abril del 2020. Pacientes Se incluyó a un total de 201 pacientes de UCI ingresados por COVID-19. Los pacientes se categorizaron en 3 grupos en función de la dosis de anticoagulación más alta recibida durante el ingreso: profiláctica, intermedia y terapéutica. Intervenciones Se comparó la incidencia de eventos trombóticos, hemorragia y mortalidad entre los grupos. Se realizaron 2 regresiones logísticas multivariables para comprobar la asociación entre los eventos trombóticos y el sangrado con el régimen anticoagulante. Principales variables de interés Eventos trombóticos, sangrado y mortalidad. Resultados De los pacientes incluidos, 78 recibieron dosis profilácticas, 94 intermedias y 29 terapéuticas. No se encontraron diferencias en los eventos trombóticos y la mortalidad entre grupos, mientras que los sangrados fueron más frecuentes en el grupo de dosis terapéutica (31%) e intermedia (15%) que en el grupo de dosis profiláctica (5%) (p <0,001 y p <0,05, respectivamente). El régimen anticoagulante fue el mayor determinante de sangrado (odds ratio 2,4;, intervalo de confianza del 95%, 1,26-4,58; p=0,008) pero no tuvo ningún impacto en los eventos trombóticos. Conclusiones Las dosis intermedias y terapéuticas parecen tener un mayor riesgo de sangrado sin una disminución de los eventos trombóticos ni la mortalidad en pacientes de UCI con COVID-19 (AU)

Role of the melanocortin system in zebrafish skin physiology.

The agouti-signaling protein (ASIP) acts as both a competitive antagonist and inverse agonist of melanocortin receptors which regulate dorsal-ventral pigmentation patterns in fish. However, the potential role of ASIP in the regulation of additional physiological pathways in the skin is unknown. The skin plays a crucial role in the immune function, acting as a physical limitation against infestation and also as a chemical barrier due to its ability to synthesize and secrete mucus and many immune effector proteins. In this study, the putative role of ASIP in regulating the immune system of skin has been explored using a transgenic zebrafish model overexpressing the asip1 gene (ASIPzf). Initially, the structural changes in skin induced by asip1 overexpression were studied, revealing that the ventral skin of ASIPzf was thinner than that of wild type (WT) animals. A moderate hypertrophy of mucous cells was also found in ASIPzf. Histochemical studies showed that transgenic animals appear to compensate for the lower number of cell layers by modifying the mucus composition and increasing lectin affinity and mucin content in order to maintain or improve protection against microorganism adhesion. ASIPzf also exhibit higher protein concentration under crowding conditions suggesting an increased mucus production under stressful conditions. Exposure to bacterial lipopolysaccharide (LPS) showed that ASIPzf exhibit a faster pro-inflammatory response and increased mucin expression yet severe skin injures and a slight increase in mortality was observed. Electrophysiological measurements show that the ASIP1 genotype exhibits reduced epithelial resistance, an indicator of reduced tissue integrity and barrier function. Overall, not only are ASIP1 animals more prone to infiltration and subsequent infections due to reduced skin epithelial integrity, but also display an increased inflammatory response that can lead to increased skin sensitivity to external infections.

Prevention of venous thromboembolism in hematologic neoplasms: an expert consensus from SEHH–SETH

Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.

Reliability of a computer-aided system in the evaluation of indeterminate ultrasound images of thyroid nodules.

Introduction: Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images. Methods: US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images. Results: In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02). Conclusions: Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

Prevention of venous thromboembolism in hematologic neoplasms: an expert consensus from SEHH-SETH.

Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.

Lupus anticoagulant is an independent risk factor for non-thrombotic in-hospital mortality in COVID-19 patients.

BACKGROUND: Thromboembolic disease is a frequent cause of death during SARS CoV-2 infection. Lupus anticoagulant (LA) appears frequently during the acute phase of infection. It is not clear whether it is merely an epiphenomenon or whether it is related to the patients' outcome. METHODS: Prospective observational cohort of 211 patients (118 women, mean age 65 years, range: 18 to 99) hospitalized for COVID-19. All patients were tested for LA at admission and retested six months after discharge. RESULTS: The LA test was positive in 128 patients (60.7%). The survival probability at 31 days was clearly worse in the LA-positive group (60%) than in the LA-negative group (90%) (P = 0.023). This notable difference in survival was confirmed by multivariate analysis (HR 3.9, 95% CI 1.04-14.5, P = 0.04). However, it was not explained by differences in thrombotic events (three in either group, P = 0.6). LA-positive patients had higher ferritin, CRP and IL-6 levels, and lower PAFI ratio and lymphocyte and platelet counts. Six months after discharge, LA was negative in the vast majority of positive cases (94%). CONCLUSION: LA is an independent predictor of in-hospital mortality in COVID-19 patients. It is associated with inflammation and disease severity but not with thromboembolic events. This marker usually disappears at six months.

Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients. DESIGN: Retrospective observational and analytical cohort study. SETTING: COVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020. PATIENTS: 201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic. INTERVENTIONS: The incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen. MAIN VARIABLES OF INTEREST: VTE, bleeding and mortality. RESULTS: 78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p<0.001 and p<0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26-4.58, p=0.008) but had no impact on VTE. CONCLUSIONS: Intermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients.

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.

Glucosensing capacity of rainbow trout telencephalon.

To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout, by in situ hybridisation, the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6 hours after i.c.v. treatment with glucose or 2-deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor and sodium-glucose linked transporter 1 (SGLT-1). We also assessed mRNA abundance of neuropeptides involved in the metabolic control of food intake (agouti-related protein, neuropeptide Y, pro-opiomelanocortin, and cocaine- and amphetamine-related transcript), as well as the abundance and phosphorylation status of proteins possibly involved in linking glucosensing with neuropeptide expression, such as protein kinase B (AkT), AMP-activated protein kinase (AMPK), mechanistic target of rapamycin and cAMP response element-binding protein (CREB). The responses obtained support the presence in the telencephalon of a glucosensing mechanism based on GK and maybe one based on LXR, although they do not support the presence of mechanisms dependent on mitochondrial activity and SGLT-1. The mechanism based on sweet taste receptor responded to glucose but in a converse way to that characterised previously in the hypothalamus. In general, systems responded only to glucose but not to glucoprivation. Neuropeptides did not respond to glucose or glucoprivation. By contrast, the presence of glucose activates Akt and inhibits AMPK, CREB and forkhead box01. This is the first study in any vertebrate species in which the response to glucose of putative glucosensing mechanisms is demonstrated in the telencephalon. Their role might relate to processes other than homeostatic control of food intake, such as the hedonic and reward system.

State of the art vs biological variability: Comparison on hematology parameters using Spanish EQAS data.

INTRODUCTION: It is important for clinical laboratories to maintain under control the possible sources of error in its analytical determinations. The objective of this work is to perform an analysis of the total error committed by laboratories using the data extracted from the Spanish External Quality Assessment Program in Hematology and to compare them with the specifications based on the biological variability proposed by the Ricós group. MATERIAL AND METHODS: We analyzed a total of 3 89 000 results during the period 2015-2016 from the following quantitative schemes of Spanish External Quality Assessment Program: complete blood count, blood coagulation tests, differential leukocyte count, reticulocytes, hemoglobin A2 , antithrombin, factor VIII, protein C, and von Willebrand factor. It has been considered as an indicator of the current performance the value of total error that 90% of laboratories are able to achieve, taking into account 75% of their results. RESULTS: We found some magnitudes whose biological variability specifications are achievable by most of the laboratories for either minimum, desirable, or optimum criteria: white blood cells, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, platelets, fibrinogen, neutrophils, lymphocytes, eosinophils, von Willebrand factor, and protein C. However, current performance for mean corpuscular hemoglobin concentration and hemoglobin A2 only allows to meet the specifications based on the state of the art. CONCLUSION: Our results reflect the feasibility of establishing specifications based on biological variability criteria or the state of the art, which may help to select the proper criteria for each parameter.

Total circulating microparticle levels are increased in patients with deep infiltrating endometriosis.

STUDY QUESTION: Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with endometriosis? SUMMARY ANSWER: The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE). WHAT IS KNOWN ALREADY: Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis. STUDY DESIGN, SIZE, DURATION: A prospective case-control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit. MAIN RESULTS AND THE ROLE OF CHANCE: Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed. LIMITATIONS, REASONS FOR CAUTION: This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle. WIDER IMPLICATIONS OF THE FINDINGS: Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the 'Plan Nacional de I + D + I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and 'Fondo Europeo de Desarrollo Regional (FEDER)' and by the grant 'Premi Fi de Residència Emili Letang 2015' from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose.

Higher levels of procoagulant microparticles in women with recurrent miscarriage are not associated with antiphospholipid antibodies.

STUDY QUESTION: Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)? SUMMARY ANSWER: cMPs in women with RM are not associated with antiphospholipid antibodies (aPLs). WHAT IS KNOWN ALREADY: Previous studies have focused on cMP levels in RM patients. Most studies have shown higher levels of cMPs in RM patients whereas others have reported lower levels. Data regarding cMPs in patients with the APS are scanty in the literature. STUDY DESIGN, SIZE, DURATION: A case-control study including three groups of patients. A total of 154 women were prospectively recruited from September 2009 to October 2013. Four patients refused to participate. The APS group consisted of 50 women that had been previously diagnosed with primary APS and had had ≥3 consecutive first trimester miscarriages. The uRM group included 52 couples with ≥3 consecutive first trimester miscarriages of unknown etiology. The fertile control (FER) group was composed of 52 healthy fertile women with no history of pregnancy losses. Miscarriage was defined as intrauterine pregnancy loss at <10 weeks' size on ultrasound. PARTICIPANTS/MATERIALS, SETTING, METHODS: Venous blood samples for coagulation studies and cMP determinations were obtained. All patients underwent a thrombophilia study. MAIN RESULTS AND THE ROLE OF CHANCE: cMP levels were significantly higher in the APS and uRM groups versus the FER group (P < 0.0001 and P = 0.009, respectively) (cMP number × 10(3)/ml plasma [mean ± SD]: APS: 18.5 ± 13.6; uRM: 16.3 ± 13.8; FER: 9.7 ± 4.6). There were no statistically significant differences in cMP levels between the APS and uRM groups. LIMITATIONS, REASONS FOR CAUTION: The sample size was arbitrarily decided according to previous studies analyzing cMPs in RM patients. Different cMP subtypes were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: The present study adds further data on the subject showing that patients with RM, irrespective of testing positive for aPLs, have increased levels of cMPs compared with healthy fertile controls. The presence of elevated cMPs in RM women may reflect an ongoing systemic pathological, albeit asymptomatic, status that can become deleterious in the setting of pregnancy. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by grant from FIS-PI11/01560 within the 'Plan Nacional de I+D+I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and the 'Fondo Europeo de Desarrollo Regional (FEDER)'. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Molecular cloning and characterization of the matricellular protein Sparc/osteonectin in flatfish, Scophthalmus maximus, and its developmental stage-dependent transcriptional regulation during metamorphosis.

SPARC/osteonectin is a multifunctional matricellular glycoprotein, which is expressed in embryonic and adult tissues that undergo active proliferation and dynamic morphogenesis. Recent studies indicate that Sparc expression appears early in development, although its function and regulation during development are largely unknown. In this report, we describe the isolation, characterization, post-embryonic developmental expression and environmental thermal regulation of sparc in turbot. The full-length turbot sparc cDNA contains 930 bp and encodes a protein of 310 amino acids, which shares 77, 75 and 80% identity with human, frog and zebrafish, respectively. Results of whole-mount in situ hybridization reveal a dynamic expression profile during post-embryonic turbot development. Sparc is expressed differentially in the cranioencephalic region; mainly in jaws, branchial arches, fin folds and rays of caudal, dorsal and anal fins. Furthermore, ontogenetic studies demonstrated that Sparc gene expression is dynamically regulated during post-embryonic turbot development, with high expression during stage-specific post-embryonic remodeling. Additionally, the effect of thermal environmental conditions on turbot development and on ontogenetic sparc expression was evaluated.

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

BACKGROUND: Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. METHODS: ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. RESULTS: SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. CONCLUSION: ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE.

Hemorragias en pacientes anticoagulados: utilidad real de los antídotos y modo de actuación con los nuevos anticoagulantes orales / Bleeding in patients on anticoagulant therapy: the real utility of antidotes and how to manage bleeding in patients on new-generation oral anticoagulants

Una de las complicaciones más temidas de los anticoagulantes son las hemorragias. Aunque en muchas ocasiones la suspensión de la anticoagulación y medidas de soporte es suficiente, en otras ocasiones exigen un tratamiento más específico. Clásicamente se han empleado los antagonistas de la vitamina K (AVK) en la prevención a largo plazo de las complicaciones tromboembólicas. Sin embargo, éstos presentan numerosas limitaciones que complican su manejo clínico. Los nuevos anticoagulantes orales, además de tener una eficacia al menos similar a los AVK con una menor incidencia de hemorragias intracraneales, no necesitan controles rutinarios de la coagulación y se pautan a dosis fijas. Sin embargo, no están exentos de presentar complicaciones hemorrágicas. Con la única diferencia de que los AVK tienen un antídoto específico, el manejo de las hemorragias con los nuevos anticoagulantes orales es muy similar al de la hemorragia asociada a los AVK (AU)

Bleeding is one of the most feared complications of anticoagulant therapy. Discontinuing the anticoagulant and establishing of support measures will often resolve the emergency, but some cases require more specific treatment. Vitamin K antagonists (VKAs) have traditionally been used for long-term prevention of thromboembolic complications, but these drugs have many limitations that complicate clinical management. The new-generation of oral anticoagulants are similar in efficacy to VKAs but are associated with a lower incidence of intracranial hemorrhage, do not require routine scheduling of laboratory tests, and can be prescribed at fixed dosages. However, these drugs are not complication-free. The management of acute bleeding is very similar for patients on either VKA or a new oralanticoagulant, with the single exception that a specific antidote is available to reverse the effect of a VKA (AU)

Involvement of melanocortin receptor accessory proteins (MRAPs) in the function of melanocortin receptors.

The melanocortin system integrates different agonists, competitive or inverse agonists, and receptors. Recent investigations have also discovered a specific system of melanocortin receptor accessory proteins (MRAPs) that are involved in the regulation of the functional expression of these receptors. MRAP1 mutations are responsible for type 2 familial glucocorticoid deficiency (FGD2), a rare autosomal disorder characterized by high plasma adrenocorticotropin hormone (ACTH) levels but severe cortisol deficiency. ACTH binds melanocortin 2 receptor (MC2R), a G protein-coupled receptor, in the adrenal gland to promote corticosteroid synthesis. In the absence of MRAP1, MC2R cannot translocate from the endoplasmic reticulum to the plasma membrane and ACTH-induced signaling is extinguished. A second MRAP protein, called MRAP2, also modulates MC2R activity. MRAPs also interact with the other melanocortin receptors, adjusting their pharmacological properties. In this paper, we briefly review the MRAP system and its interaction with melanocortin receptors.