Manejo de la tromboflebitis superficial en la mujer embarazada

Superficial vein thrombosis (SVT) has traditionally been considered a benign condition. However, current evidence suggests that thrombosis will spread into the deep vein system in a significant proportion of cases, particularly when the thrombus occupies the proximal long saphenous vein. Its presentation in pregnancy is an added difficulty. This case represents the complex management of a condition for which diagnostic prediction tools are lacking. Ultrasound examination plays a key role, especially in pregnant patients, for whom evidence supporting the diagnosis and treatment of venous thromboembolic disease is weaker than for the rest of patients. We present the case of a pregnant woman of 9 weeks with SVT and we discussed her management.La trombosis venosa superficial se ha considerado tradicionalmente como una afección benigna. Sin embargo, la evidencia actual sugiere que una proporción significativa de casos se propagará al sistema venoso profundo, particularmente cuando el trombo ocupa la vena safena larga proximal. Su presentación en el embarazo supone una dificultad añadida. Este caso representa la complejidad en el manejo de una patología sobre la que no hay herramientas de predicción diagnóstica, y donde la ecografía juega un papel clave, en especial en pacientes embarazadas, en quienes las evidencias que soportan el diagnóstico y tratamiento de la enfermedad tromboembólica venosa son más débiles que en el resto de los pacientes. Presentamos el caso de una gestante de 9 semanas con trombosis venosa superficial y discutimos su manejo

Manejo de la mujer embarazada con síndrome antifosfolípido obstétrico y trombótico

Antiphospholipid syndrome is a systemic autoimmune disease in which the underlying pathological process described is the thrombosis in any vascular place and/or obstetric morbidity. Given the variability of its clinical symptoms we can speak of two variants of the same disease whose management is different in terms of follow-up and treatment. We present a case of a pregnancy in the context of a complete antiphospholipid syndrome (thrombotic and obstetric). The planning of pregnancy and childbirth, the close and coordinated follow-up, as well as the individualization of the treatment were essential to carry out the gestation.El síndrome antifosfolípido es una enfermedad autoinmune sistémica que se define por la trombosis en cualquier lecho vascular y/o la morbilidad obstétrica. Dada la variabilidad en sus manifestaciones clínicas, podemos hablar de dos variantes de una misma entidad, síndrome antifosfolípido trombótico y síndrome antifosfolípido obstétrico, cuyo manejo presenta diferentes matices en cuanto a seguimiento y tratamiento. Presentamos un caso de una gestación en el contexto de un síndrome antifosfolípido completo (trombótico y obstétrico). La planificación del embarazo y el parto, el seguimiento cercano y coordinado, así como la individualización del tratamiento resultaron esenciales para llevar a buen término la gestación

Cáncer renal con trombosis de vena renal y vena cava inferior

Venous thromboembolic disease is a frequent and serious clinic complication in cancer patients. Risk is higher in those with metastatic disease, and thrombosis related with cancer is associated with lower survival rates. Anticoagulation is the main treatment, usually continued for a long time, carrying risk for bleeding events. Despite anticoagulation, a high rate of recurrences is described. Venous thrombosis and cancer is a major therapeutic challenge and requires a comprehensive management. We present the case of a 55-year-old male with clear cell renal carcinoma and associated venous thromboembolic disease.La enfermedad tromboembólica venosa es una de las complicaciones más frecuentes y graves de los pacientes oncológicos. La incidencia es mayor en tumores con enfermedad metastásica y su desarrollo se relaciona con una menor supervivencia. La anticoagulación, que es el tratamiento indicado, en la gran mayoría de los casos debe mantenerse a largo plazo, con el riesgo hemorrágico que esto conlleva. Además, la trombosis venosa asociada al cáncer presenta una elevada tasa de recurrencias pese a la anticoagulación. El manejo de la trombosis venosa en el cáncer es complejo y precisa una aproximación multidisciplinar. Presentamos el caso de un varón de 55 años con un carcinoma renal de células claras y enfermedad tromboembólica venosa asociada

Página web orientada a la evaluación “in silico” de nuevas sustancias con interés biológico IV

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study)

Background Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities. Methods 1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC. Results Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10−6). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differsignificantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese). Conclusions In coronary patients, a metabolically abnormal phenotype is associated with a greater IMTCC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesit

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Página web orientada a la evaluación in silico de nuevas sustancias con interés biológico (parte V)

Sección Deptal. de Farmacología y Toxicología (Veterinaria)Fac. de VeterinariaFALSEsubmitte

Ratiometric Two-Photon Near-Infrared Probe to Detect DPP IV in Human Plasma, Living Cells, Human Tissues, and Whole Organisms Using Zebrafish

DPP IV, otherwise known as CD26 lymphocyte T surface antigen, is a transmembrane glycoprotein also found in circulation in the blood. It plays an important role in several processes like glucose metabolism and T-cell stimulation. Moreover, it is overexpressed in renal, colon, prostate, and thyroid human carcinoma tissues. It can also serve as a diagnostic in patients with lysosomal storage diseases. The biological and clinical importance of having readouts for the activity of this enzyme, in physiological and disease conditions, has led us to design a near-infrared (NIR) fluorimetric probe that also has the characteristics of being ratiometric and excitable by two simultaneous NIR photons. The probe consists of assembling an enzyme recognition group (Gly-Pro) (Mentlein, 1999; Klemann et al., 2016) on the two-photon (TP) fluorophore (derivative of dicyanomethylene- 4H-pyran, DCM-NH2) disturbing its NIR characteristic internal charge transfer (ICT) emission spectrum. When the dipeptide group is released by the DPP IV-specific enzymatic action, the donor−acceptor DCM-NH2 is restored, forming a system that shows high ratiometric fluorescence output. With this new probe, we have been able to detect, quickly and efficiently, the enzymatic activity of DPP IV in living cells, human tissues, and whole organisms, using zebrafish. In addition, due to the possibility of being excited by two photons, we can avoid the autofluorescence and subsequent photobleaching that the raw plasma has when it is excited by visible light, achieving detection of the activity of DPP IV in that medium without interference.FEDER/Junta de Andaluc?a- Consejer?a de Transformaci?n Econ?mica, Industria, Con- ocimiento y Universidades/Proyecto A-FQM-230-UGR20 PID2020-114256RB-I00Spanish Government FPU17/0474

New ICT-Based Ratiometric Two-Photon near Infrared Probe for Imaging Tyrosinase in Living Cells, Tissues, and Whole Organisms

Melanoma is a type of highly malignant and metastatic skin cancer. In situ molecular imaging of endogenous levels of the melanoma biomarker tyrosinase (TYR) may decrease the likelihood of mortality. In this study, we proposed the weakly fluorescent probe 1-(4-(2-(4-(dicyanomethylene)-4H-chromen-2-yl)vinyl)phenyl)-3-(4-hydroxybenzyl)urea (DCM-HBU), which releases a strong red-shifted fluorescent signal after a TYR-mediated oxidation followed by hydrolysis of the urea linkage. The large Stokes shift of the dye is owed to the recovery of the intramolecular charge transfer (ICT) effect. The resulting probe derivate shows a highly ratiometric fluorescence output. Furthermore, the simultaneous excitation by two near-infrared (NIR) photons of the released derivative of dicyanomethylene-4H-pyran (DCM-NH2) fluorophore could avoid the usual drawbacks, such as cellular absorption, autofluorescence, and light scattering, due to an usually short wavelength of the excitation light on biological systems, resulting in images with deeper tissue penetration. In addition, the probe is useful for the quantitative sensing of TYR activity in vivo, as demonstrated in zebrafish larvae. This new ratiometric two-photon NIR fluorescent probe is expected to be useful for the accurate detection of TYR in complex biosystems at greater depths than other one-photon excited fluorescent probes