Role of sCD40L in the prediction of super response to cardiac resynchronization therapy / Rol de sCD40L en la predicción de súper respuesta a la terapia de resincronización cardiaca

Background: The aim of this paper is to analyze the roleof the biomarkers Interleukin 6, Tumoral Necrosis Factor α,sCD40L, high sensitive Troponin T, high sensitive C-ReactiveProtein and Galectin-3 in predicting super response (SR) toCardiac Resynchronization Therapy (CRT), as they have notbeen studied in this field before. Methods: Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year.SR was defined as reduction in LVESV ≥ 30% at one yearfollow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. Results: 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p = 0.04),suffering from less ischemic cardiomyopathy (13 vs. 63%,p < 0.0001) and lateral (0 vs. 18%, p = 0.03), inferior (4 vs.33%, p = 0.01) and posterior infarction (0 vs. 22%, p = 0.01);absence of mitral regurgitation (47% vs. 22%, p = 0.04), wider QRS width (157.7 ± 22.9 vs. 140.8 ± 19.2ms, p = 0.01), higher concentrations of sCD40L (6.9 ± 5.1 vs. 4.4 ± 3.3 ng/mL,p = 0.02), and left ventricular lead more frequent in lateralmedial position (69 vs. 26%, p = 0.002). QRS width, lateralmedial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showeda moderate direct correlation with SR (r = 0.39, p = 0.02) andwith the reduction of LVESV (r = 0.44, p = 0.02). Conclusion: sCD40L correlates significantly with SR to CRT.QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SRin this cohort.(AU)

Fundamento: Analizar los biomarcadores Interleuquina 6,factor de necrosis tumoral α, sCD40L, troponina T hipersensible, proteína Creactiva hipersensible y galectina-3 en lapredicción de súper-respuesta (SR) a la terapia de resincronización cardiaca (TRC), ya que no han sido valorados conanterioridad. Material y métodos: Se recopilaron datos clínicos, electrocardiográficos y ecocardiográficos preimplante y al año.Se definió SR como disminución del VTSVI ≥ 30% al añode seguimiento. Las muestras sanguíneas fueron extraídaspreimplante. Se realizó regresión logística multivariante ycurvas ROC. Resultados: Se incluyeron 50 pacientes, 23 (46%) fueronSR.Las características relacionadas con la SR fueron: ser mujer (35 vs. 11%, p = 0,04), sufrir menos cardiopatía isquémica(13 vs. 63%, p < 0,0001) e infarto lateral (0 vs. 18%, p = 0,03),inferior (4 vs. 33%, p = 0,01) y posterior (0 vs. 22%, p = 0,01); ausencia de insuficiencia mitral (47% vs. 22%, p = 0,04), mayor anchura del QRS (157,7 ± 22,9 vs. 140,8 ± 19,2 ms, p = 0,01), mayorconcentración de sCD40L (6,9 ± 5,1 vs. 4,4 ± 3,3 ng/mL, p = 0,02),y electrodo ventricular izquierdo más frecuentemente en posición lateral media (69 vs. 26%, p = 0,002). El QRS, la posiciónlateral media del electrodo y la ausencia de insuficiencia mitral fueron predictores independientes de SR. sCD40L mostróuna correlación moderada directa con SR (r = 0,39, p = 0,02) ycon la disminución del VTSVI (r = 0,44, p = 0,02). Conclusiones: sCD40L se correlaciona significativamentecon SR a la TRC. El QRS, la ausencia de insuficiencia mitraly la posición lateral media del electrodo son predictores independientes de SR en esta cohorte.(AU)

Role of sCD40L in the prediction of super-response to cardiac resynchronization therapy.

BACKGROUND: The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor a, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. METHODS: Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV = 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. RESULTS: 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p?=?0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p?

Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.

PURPOSE: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients. METHODS: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. RESULTS: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE. CONCLUSION: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.

[MELALIB 15: A retrospective observational study of 383 cases of melanoma diagnosed by dermatologists in private practice]. / MELALIB15 : étude observationnelle rétrospective de 383 mélanomes dépistés par des dermatologues libéraux.

BACKGROUND: Early detection of melanoma constitutes a major challenge and is a common reason for dermatological consultations. There is no recent data on melanomas diagnosed in the private medical sector in France, nor on the circumstances of diagnosis. PATIENTS AND METHODS: This was a retrospective observational study on records collating data on all new consecutive cases of melanoma diagnosed between January 2015 and June 2018, in the private sector only, by volunteer dermatologists belonging to the association for continuing medical education, "Dermatologie Paris XV". A data collection sheet was prepared on which to record information about the dermatologist, the patient, the main complaint, the characteristics of the melanoma, and the initial treatment given, using the computerized list provided by our dermatopathology offices. RESULTS: The study involved 383 cases of melanoma, 37% in situ and 63% invasive, which consisted chiefly of superficial spreading melanoma. The median age of the cohort was 61 years and patients were predominantly female (58%). Follow-up of high-risk patients and complete routine examination (in those consulting for another reason) resulted in direct detection by a dermatologist of 202 of the 383 melanomas (52.7%); these melanomas had a lower median Breslow index than the rest of the cohort and were thin in the main. When patients consulted for a suspect lesion (139 cases), the lesion had been identified mostly by either the patient or by a relative (61% of cases). The decision to consult was made chiefly by the patients themselves, and the Breslow index was thicker. An initial consultation for nevus screening resulted in diagnosis of 42 melanomas, i.e. only 11% of the cohort. Dermoscopy was performed by 92% of the dermatologists participating in the study. Melanoma excision was performed in the office by the practitioner in 75% of cases, and management was validated at multidisciplinary meetings in 65% of cases. CONCLUSION: In terms of French primary care, dermatologists in private practice play a key role in ensuring early detection and initial management of melanoma.

Delta Opioid Receptors: Learning and Motivation.

Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward. Remarkably, DOR seems to play a key role in balancing hippocampal and striatal functions, with major implications for the control of cognitive performance and motor function under healthy and pathological conditions.

Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening.

OBJECTIVE: To determine the effects of a 1-year quality-improvement (QI) process to reduce door-to-needle (DTN) time in a secondary general hospital in which multimodal MRI screening is used before tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke (AIS). METHODS: The QI process was initiated in January 2015. Patients who received intravenous (iv) tPA<4.5h after AIS onset between 26 February 2015 to 25 February 2016 (during implementation of the QI process; the "2015 cohort") were identified (n=130), and their demographic and clinical characteristics and timing metrics compared with those of patients treated by iv tPA in 2014 (the "2014 cohort", n=135). RESULTS: Of the 130 patients in the 2015 cohort, 120 (92.3%) of them were screened by MRI. The median DTN time was significantly reduced by 30% (from 84min in 2014 to 59min; P<0.003), while the proportion of treated patients with a DTN time≤60min increased from 21% to 52% (P<0.0001). Demographic and baseline characteristics did not significantly differ between cohorts, and the improvement in DTN time was associated with better outcomes after discharge (patients with a 0-2 score on the modified rankin scale: 59% in the 2015 cohort vs 42.4% in the 2014 cohort; P<0.01). During the 1-year QI process, the median DTN time decreased by 15% (from 65min in the first trimester to 55min in the last trimester; P≤0.04) with a non-significant 1.5-fold increase in the proportion of treated patients with a DTN time≤60min (from 41% to 62%; P=0.09). CONCLUSION: It is feasible to deliver tPA to patients with AIS within 60min in a general hospital, using MRI as the routine screening modality, making this QI process to reduce DTN time widely applicable to other secondary general hospitals.

The antiviral potency of Fagus sylvatica 4OMe-glucuronoxylan sulfates.

Herpes simplex virus belongs to Herpesviridae family and causes infection of humans from ancient times. 4OMe-glucuronoxylans as the renewable biopolymers can be promising glycomaterials for various applications in pharmacy. Control enzymatic degradation of the native 4OMe-glucuronoxylan (GX1) followed by targeted sulfation procedure afforded a range of 4OMe-glucuronoxylan sulfates differed in the degree of sulfation (10-16%) and molecular mass (21,000-5000g/mol; GXS1>GXS2>GXS3>GXS4). Antiviral activity tests on GXS1-4 against herpes simplex virus (HSV) types 1 and 2 revealed the positive effect of all compounds against strains of herpes virus. Of them, the compounds GXS1 and GXS4 were shown to be the most active for both HSV serotypes. The antiviral activity of GXS1 and GXS4 was similar to those of heparin or dextran sulfate, used as reference compounds. It was found that GXS1 and GXS4 were active as well against Polio and dengue viruses, however, on a smaller scale. The mode of antiviral action of 4OMe-glucuronoxylan sulfates is due to inhibition of the virus binding to the cell receptors.

Estimación de la prevalencia de infección tuberculosa latente en pacientes con psoriasis en placas moderada a grave en España. Estudio Latent / Estimation of the prevalence of latent tuberculosis infection in patients with moderate to severe plaque psoriasis in Spain: The Latent study

INTRODUCCIÓN Y OBJETIVO: Los agentes biológicos anti-TNF usados para el tratamiento de la psoriasis moderada y grave pueden incrementar el riesgo de desarrollar tuberculosis activa en pacientes con infección tuberculosa latente. El objetivo principal de este estudio fue estimar la prevalencia de infección tuberculosa latente en pacientes con psoriasis en placas moderada y grave en consultas de dermatología en España. MATERIAL Y MÉTODO: Estudio epidemiológico, no intervencionista, de corte transversal y ámbito nacional, realizado en España en 2011-2012. Se incluyeron pacientes con psoriasis en placas moderada y grave, a los que se les había realizado en los 2 años previos a su inclusión en el estudio al menos una prueba de tuberculina y/o una prueba de liberación de IFN-γ mediante la técnica de ELISA QuantiFERON®-TB gold In Tube. RESULTADOS: Se incluyeron 440 pacientes evaluables. Se había realizado una prueba de tuberculina al 97,7% de los pacientes, resultando positiva en el 23%. En 238 pacientes con una primera prueba negativa se realizó un booster, que fue positivo en el 5%. Se realizó la determinación del QuantiFERON®-TB al 16,8% de los pacientes, resultando positivo en el 20,5%; en 2 de estos pacientes la prueba de la tuberculina había sido negativa. En el total de la muestra, la prevalencia de infección tuberculosa latente fue del 26,6%. El grado de concordancia entre la prueba de tuberculina y el QuantiFERON®-TB fue medio (índice kappa = 0,516; p < 0,001). CONCLUSIONES: La prevalencia de infección tuberculosa latente estimada en este estudio fue similar a la comunicada previamente en España

BACKGROUND AND OBJECTIVE: Anti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. MATERIAL AND METHOD: Non-interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-γ release assay (IGRA) based on enzyme-linked immunosorbent assay (QuantiFERON® TB Gold In-Tube) in the 2 years preceding the study. RESULTS: Data for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (Kappa=0.516; P<.001). CONCLUSIONS: The prevalence of LTBI in this study was similar to previous estimates for Spain

Estimation of the prevalence of latent tuberculosis infection in patients with moderate to severe plaque psoriasis in Spain: The Latent study.

BACKGROUND AND OBJECTIVE: Anti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. MATERIAL AND METHOD: Non-interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-γ release assay (IGRA) based on enzyme-linked immunosorbent assay (QuantiFERON(®) TB Gold In-Tube) in the 2 years preceding the study. RESULTS: Data for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (κ=0.516; P<.001). CONCLUSIONS: The prevalence of LTBI in this study was similar to previous estimates for Spain.

[In-transit metastasis in melanoma: Efficacy of topical imiquimod combined with carbon dioxide laser or with electrocautery]. / Métastases en transit du mélanome : efficacité de l'imiquimod topique combiné au laser CO2 ou à l'électrocoagulation.

BACKGROUND: In-transit metastases in cutaneous melanoma are common and difficult to manage. Therapy is mainly palliative. Use of topical imiquimod has been assessed for surface metastases. PATIENTS AND METHODS: We report on four patients with cutaneous melanoma metastases treated with topical imiquimod associated with carbon dioxide laser in the first two patients and with electrocoagulation in the two others. For two patients, we noted complete regression of the lesions after 15 and 18 months. For the two others, treatment was stopped after 9 to 10 months because of progression of subcutaneous metastasis and distant metastasis. DISCUSSION: Topical imiquimod is an alternative treatment used in superficial in-transit metastasis of melanoma. Its use as a monotherapy is sometimes ineffective. We elected to use combined pre-treatment with carbon dioxide laser or electrocoagulation in order to potentiate the action of imiquimod. This simple and inexpensive therapeutic strategy constitutes a palliative treatment that can allow prolonged local control of cutaneous metastasis.

Increased liver stiffness values in patients with heart failure.

BACKGROUND: Liver stiffness has been claimed to be increased in patients with heart failure. AIMS: To determine the magnitude of this increase in liver stiffness, and to clarify whether it is related to the degree of heart failure or not. METHODS: Twenty-six patients were prospectively collected, and divided in groups CHF (those with compensated chronic heart failure) and AHF (those with acute decompensated heart failure). Patients underwent routine blood chemistries, pro-BNP determination, echocardiography and transient elastography during outpatient care (group CHF) or at hospital admission (group AHF). Blood chemistries, pro-BNP and transient elastography were repeated in patients in group AHF before being discharged. RESULTS: Correlation between liver stiffness and pro-BNP levels was statistically significant (Rho = 0.747, p = 0.001). Patients in group CHF had lower values of liver stiffness and pro-BNP when compared with patients in group AHF at admission. Median liver stiffness and pro-BNP values were 6.5 vs 14.4 kPa (p = 0.009) and 1511 vs 3535 pg/ml (p = 0.025) respectively. After clinical compensation, liver stiffness decreased in all patients in group AHF. Liver stiffness was 14.4 kPa at admission and 8.2 kPa at discharge (p = 0.008). Pro-BNP values also decreased from a median of 3535 pg/ml to a median of 1098 pg/ml (p = 0.025). CONCLUSIONS: Patients with heart failure have increased liver stiffness, that appears to be related with the severity of heart failure.

A Case of DRESS Syndrome Induced by Dipyrone

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Síndrome de hipersensibilidad inducido por sulfasalazina asociado a reactivación de VHH-6 e inducción de síndrome antifosfolípido / Sulfasalazine-Induced Hypersensitivity Syndrome Associated With Human Herpesvirus 6 Reactivation and Induction of Antiphospholipid Syndrome

El síndrome de hipersensibilidad inducido por fármacos (DIHS) se engloba dentro de los cuadros toxicodérmicos con afectación sistémica, cuya sospecha obliga a la retirada lo más precoz posible del fármaco que consideremos pueda estar implicado, que puede haber sido introducido hasta tres meses antes. Es importante el despistaje de la reactivación del virus herpes humano (VHH) 6, tanto por su valor diagnóstico como por el pronóstico de gravedad que supone. Por otro lado, esta reactivación no contraindica que el tratamiento pueda llevarse a cabo con corticoides sistémicos, que además, deberán retirarse lentamente para evitar recaídas. Debería pensarse asimismo en la posibilidad de la presencia de anticuerpos antifofolipídicos en los casos en que apareciera trombopenia, alteración en la hemostasia o cuadros trombóticos asociados, como también tener en cuenta el desarrollo de procesos autoinmunes como secuela del cuadro, que requiere de monitorización y seguimiento a medio-largo plazo, a pesar de la resolución completa del cuadro. Describimos un nuevo caso donde se muestra la reactivación del VHH-6, la activación de anticuerpos anticardiolipina y la inducción de anticuerpos anti-tiroperoxidasa (anti-TPO) (AU)

Drug-induced hypersensitivity syndrome is a toxicoderma with systemic involvement. Suspicion of this disorder obliges rapid withdrawal of the suspected drug, which may have been introduced up to 3 months earlier. Screening for human herpesvirus (HHV) 6 reactivation is important both for its diagnostic value and for its association with a poor prognosis. Reactivation of this virus is not a contraindication for systemic corticosteroid treatment, which should be tapered slowly in order to avoid recurrence. The possible appearance of antiphospholipid antibodies must also be considered in those cases associated with thrombocytopenia, altered hemostasis, or thrombotic events. Autoimmune disorders may also develop as a sequela of the condition. Medium-to-long-term follow-up is required even after complete resolution of the condition. We describe a new case of sulfasalazine-induced hypersensitivity syndrome associated with HHV-6 reactivation and the induction of anticardiolipin and anti-thyroid peroxidase antibodie (AU)

[Sulfasalazine-induced hypersensitivity syndrome associated with human herpesvirus 6 reactivation and induction of antiphospholipid syndrome]. / Síndrome de hipersensibilidad inducido por sulfasalazina asociado a reactivación de VHH-6 e inducción de síndrome antifosfolípido.

Drug-induced hypersensitivity syndrome is a toxicoderma with systemic involvement. Suspicion of this disorder obliges rapid withdrawal of the suspected drug, which may have been introduced up to 3 months earlier. Screening for human herpesvirus (HHV) 6 reactivation is important both for its diagnostic value and for its association with a poor prognosis. Reactivation of this virus is not a contraindication for systemic corticosteroid treatment, which should be tapered slowly in order to avoid recurrence. The possible appearance of antiphospholipid antibodies must also be considered in those cases associated with thrombocytopenia, altered hemostasis, or thrombotic events. Autoimmune disorders may also develop as a sequela of the condition. Medium-to-long-term follow-up is required even after complete resolution of the condition. We describe a new case of sulfasalazine-induced hypersensitivity syndrome associated with HHV-6 reactivation and the induction of anticardiolipin and anti-thyroid peroxidase antibodies.

Loss of human beta-defensin 1, 2, and 3 expression in oral squamous cell carcinoma.

INTRODUCTION: Human beta-defensins (HBDs) are cationic, antimicrobial peptides produced by epithelial cells and involved in various aspects of the innate and acquired immune responses. They are expressed by oral tissues as constitutive and inducible genes. Recently, single nucleotide polymorphisms (SNPs) of beta-defensins have been correlated with increased susceptibility to certain diseases. Studies have reported altered expression of beta-defensins in cancers suggesting their involvement in carcinogenesis. The purpose of this study was to evaluate the regulation of HBD-1 (also published as DEFB1), HBD-2 (DEFB4) and HBD-3 (DEFB103A) (http://www.genenames.org/index.html) and HBD-1 SNPs in oral squamous cell carcinoma cell lines (OSCC) and healthy gingival keratinocytes. METHODS: beta-defensin expression was quantitatively assessed using real-time polymerase chain reactions in OSCC and control cell lines after exposure to interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma. Control data were obtained in a previous study. DNA from 19 OSCC cell lines and 44 control subjects were extracted and the HBD-1 region spanning the 5' untranslated region to the first intron was sequenced and analysed for SNP identification and distribution. RESULTS: HBD-1 and HBD-2 basal messenger RNA expression were significantly lower in OSCC. In addition, the ability to be induced was significantly reduced in OSCC for all three beta-defensins. Four HBD-1 SNPs were differentially distributed between cancer and control populations. Genotype distribution at the HBD-1 locus also suggested loss of heterozygosity in OSCC. CONCLUSIONS: The genetic variation observed in OSCC compared with that in control cell lines may account for differences in beta-defensin expression. These results suggest a putative role for beta-defensins in carcinogenesis and indicate that beta-defensins may be useful markers of OSCC.