Pregnancy outcome in patients with a medical history of immunoglobulin A vasculitis: a case-control study.

OBJECTIVE: Data on obstetric outcomes in patients with a history of immunoglobulin A vasculitis (IgA-V) are lacking. The aim of this study was to assess maternal, neonatal, and vasculitis outcomes during pregnancy. METHOD: We conducted a French retrospective case-control study. Pregnancies of patients with a history of IgA-V (cases) were retrospectively studied and compared to pregnancies in women who developed IgA-V after their pregnancies and to pregnancies in healthy women (controls). RESULTS: Twenty-six pregnancies in patients with a history of IgA-V were included and compared to 15 pregnancies in women who later developed IgA-V and 52 pregnancies in healthy women. Both gestational hypertension and pre-eclampsia were more frequent in the case group than in the other groups (23% vs 0% vs 0%, p < 0.01; 12% vs 7% vs 0%, p = 0.04). Hypertensive disorder of pregnancy occurred more frequently in patients with pre-existing kidney disease (78% vs 12%, p < 0.01). Caesarean section was more often performed in the case group than in the other groups (27% vs 0% vs 10%, p = 0.04). No foetal loss or maternal deaths occurred. There were no differences in delivery term or birth weight. No vasculitis flares were observed during pregnancy. CONCLUSION: Women with a history of IgA-V appear to be at higher risk for gestational hypertension and pre-eclampsia, especially in cases with renal involvement; however, both mother and newborn outcomes appear to be favourable.

Contribution of nuclear medicine to the diagnosis and management of primary brain tumours.

Positron emission tomography (PET) is a powerful tool that can help physicians manage primary brain tumours at diagnosis and follow-up. In this context, PET imaging is used with three main types of radiotracers: 18F-FDG, amino acid radiotracers, and 68Ga conjugated to somatostatin receptor ligands (SSTRs). At initial diagnosis, 18F-FDG helps to characterize primary central nervous system (PCNS) lymphomas and high-grade gliomas, amino acid radiotracers are indicated for gliomas, and SSTR PET ligands are indicated for meningiomas. Such radiotracers provide information on tumour grade or type, assist in directing biopsies and help with treatment planning. During follow-up, in the presence of symptoms and/or MRI modifications, the differential diagnosis between tumour recurrence and post-therapeutic changes, in particular radiation necrosis, may be challenging, and there is strong interest in using PET to evaluate therapeutic toxicity. PET may also contribute to identifying specific complications, such as postradiation therapy encephalopathy, encephalitis associated with PCNS lymphoma, and stroke-like migraine after radiation therapy (SMART) syndrome associated with glioma recurrence and temporal epilepsy, originally illustrated in this review. This review summarizes the main contribution of PET to the diagnosis, management, and follow-up of brain tumours, specifically gliomas, meningiomas, and primary central nervous system lymphomas.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Increase of precuneus metabolism correlates with reduction of PTSD symptoms after EMDR therapy in military veterans: an 18F-FDG PET study during virtual reality exposure to war.

PURPOSE: The prevalence of posttraumatic stress disorder (PTSD) is higher among veterans, and can lead to disastrous consequences such as suicide. Eye movement desensitization and reprocessing (EMDR) is recommended in first-line psychotherapies for PTSD. Virtual reality exposure (VRE) coupled with 18F-FDG PET imaging can highlight the activated brain regions during stress exposure. The objective of this study is to identify, after EMDR therapy, the regions of brain metabolism that evolve during the stress exposure of a war scene with symptomatic remission in a group of military veterans suffering from PTSD, and to secondarily search for predictive metabolic features. METHODS: We recruited 15 military veterans suffering from PTSD who performed an 18F-FDG PET sensitized by the exposure to a virtual war scene, before (T0) and after (T1) EMDR therapy. Statistical parametric mapping was used to compare brain metabolism before and after treatment and to study correlations between metabolism and evolution scores on PTSD clinical scales (PTSD Checklist Scale, PCLS; Clinician-Administered PTSD Scale, CAPS). RESULTS: The metabolic activity of the precuneus was increased after EMDR therapy (p < 0.005 uncorrected, k > 180) and correlated with clinical improvement with the CAPS scale (r = -0.73 and p < 0.001). Moreover, the precuneus metabolic value before therapy predicted the clinical improvement on the PCLS scale (T1-T0) after EMDR (r = -0.667 and p < 0.006). CONCLUSION: The clinical improvement in military patients with PTSD after EMDR is related to increased precuneus metabolism upon VR stress exposure.

Harmonization of GEOV2 fAPAR time series through MODIS data for global drought monitoring.

The temporal consistency of the fAPAR GEOV2 full time series (constituted by data derived from SPOT-VGT1/2 and PROBA-V) is analyzed against the single-sensor MODIS dataset, with a particular focus on the most recent fAPAR anomalies (z-scores) produced from PROBA-V in the period 2014-2017. The intercomparison highlights a systematic overestimation of GEOV2 fAPAR z-scores when compared to MODIS fAPAR, likely related to the observed positive bias (over 90% of the domain) in the PROBA-V vs. SPOT-VGT1/2 relationship. A simple two-step harmonization procedure has been proposed to remove this discrepancy, based on two separate linear corrections of SPOT-VGT1/2 (2001-2013) and PROBA-V (2014-2017) data with respect to MODIS, followed by a time lag correction. The harmonized GEOV2 time series preserves the overall dynamic of fAPAR, while removing the sensor bias and improving the consistency with MODIS data. The fAPAR anomalies from the harmonized GEOV2 time series provide unbiased estimates of z-scores that are overall well correlated (R = 0.55 ± 0.25) with the MODIS fAPAR anomalies.

Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives.

This review aims to synthesize all the available data on brain molecular imaging, such as single-photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose positron emission tomography (FDG-PET), in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major innovation remains its ictal imaging value. On the other hand, FDG-PET, which has higher spatial resolution and lower background activity than SPECT, enables glycolytic metabolism to be identified in interictal states. Therefore, interictal FDG-PET has greater sensitivity than interictal SPECT, especially in temporal lobe epilepsies (TLEs). Thus, 18F-FDG-PET is a necessary step in the presurgical evaluation of TLEs, but also of extratemporal epilepsies (ETEs), contributing to >30% of the decision to undertake surgery. In addition, FDG-PET has particular diagnostic value in focal epilepsies showing normal magnetic resonance imaging (MRI). PET also has good prognostic value for post-surgical outcomes as well as cognitive impairment, especially in cases where the hypometabolism extent is limited. Moreover, the notion of an epileptic network is well highlighted by functional PET imaging, allowing better understanding of the pathological substrates of these disorders. Future development of quantitative analysis software and of novel radiotracers and cameras will certainly enhance its clinical usefulness.

IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas.

PURPOSE: The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and 18F-FDOPA uptake on PET in newly diagnosed gliomas. METHODS: A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone 18F-FDOPA PET at an initial stage before surgery and histological diagnosis. 18F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). RESULTS: Patients with IDH mutation showed higher 18F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). CONCLUSION: This study showed paradoxically higher 18F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of 18F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.

[McArdle's disease revealed by acute low back pain]. / Une maladie de McArdle révélée par une lombalgie aiguë.

INTRODUCTION: McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency. CASE REPORT: We report the case of a 17-year-old male patient who was referred to the emergency department for the management of acute inflammatory low back pain, without traumatic context, associated with an increase of CK at 66,336 UI/L (N<192UI/L) and a CRP at 202mg/L. The immunological assessment was negative and the spinal MRI showed images in favor of necrotizing fasciitis affecting the erector spinae muscles, among others. Faced with the description of difficulties in practicing physical activities since childhood and a non-ischaemic forearm exercise test showing no elevation in lactacidemia, genetic tests were carried out, finding two heterozygous variants in the PYGM gene: c.1963G>A (p.Glu655Lys) class 5 and c.2178-1G>A class 4, confirming the diagnosis of McArdle disease. DISCUSSION: GSD 5 is a disease characterized essentially by muscular fatigability during exercise. The case reported here is original in the clinical circumstances leading to the diagnosis, i.e., inaugural acute low back pain with rhabdomyolysis. This symptomatology had already been described before, but in a patient whose diagnosis was already known. Spinal MRI showed non-specific muscle inflammation and necrosis. Muscle biopsy only found necrosis but no pathological elements typical of the diagnosis. If the symptoms are suggestive, it may be preferable to directly perform a non-ischaemic forearm exercise test, in order to go directly to molecular genetic analysis. There is no specific curative treatment of GSD 5. However, some measures can be implemented to limit the symptoms, such as learning physical exercises, limiting intense efforts and adopting dietary recommendations.

[A late onset diagnosis of giant cell arteritis in remission]. / Diagnostic tardif d'une artérite à cellules géantes en rémission.

Giant-cell arteritis (GCA) is a classical cause of chronical inflammation (CI) in the elderly, causing headaches, scalp hypersensitivity and jaw claudication. We describe a patient with a GCA revealed with a year-long biological inflammation and weight loss. Diagnosis was performed on a systematic temporal artery biopsy showing typical histological features. No treatment was intended as the patient had a spontaneous remission, maintained at one year of follow-up. This case highlights the benefit of a systematic temporal artery biopsy to explore CI and reminds us that GCA may undergo spontaneous remission.

Molybdenum-Iodine Cluster Loaded Polymeric Nanoparticles Allowing a Coupled Therapeutic Action with Low Side Toxicity for Treatment of Ovarian Cancer.

The ability of cancer cells to develop resistance to anti-cancer drugs, known as multidrug resistance, remains a major cause of tumor recurrence and cancer metastasis. This work explores the double mechanism of toxicity of (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a molybdenum cluster compound, namely Cs2[{Mo6I8}(OOCC2F5)6] (CMIF). Hemocompatibility and biocompatibility assays show the safe potential of CMIF loaded nanoparticles (CNPs) as delivery systems intended for tumor targeting for PDT of ovarian cancer with a slight hemolytic activity and a lack of toxicity up to 50 µM CMIF concentration. Cellular uptake shows a preferential uptake of CNPs in lysosomes, which is not interfering with CMIF activity. The double mechanism of CNPs consists in a production of ROS and a DNA damage activity, from 5 µM and 0.5 µM respectively (CMIF concentration). The cellular death mechanism comprises 80% of necrosis and 20% of direct apoptosis by direct DNA damages. This work confirms CMIF loaded PLGA nanoparticles as an efficient and relevant delivery system for PDT.

The pons as reference region for intensity normalization in semi-quantitative analysis of brain 18FDG PET: application to metabolic changes related to ageing in conventional and digital control databases.

BACKGROUND: The objective of the study is to define the most appropriate region for intensity normalization in brain 18FDG PET semi-quantitative analysis. The best option could be based on previous absolute quantification studies, which showed that the metabolic changes related to ageing affect the quasi-totality of brain regions in healthy subjects. Consequently, brain metabolic changes related to ageing were evaluated in two populations of healthy controls who underwent conventional (n = 56) or digital (n = 78) 18FDG PET/CT. The median correlation coefficients between age and the metabolism of each 120 atlas brain region were reported for 120 distinct intensity normalizations (according to the 120 regions). SPM linear regression analyses with age were performed on most significant normalizations (FWE, p < 0.05). RESULTS: The cerebellum and pons were the two sole regions showing median coefficients of correlation with age less than - 0.5. With SPM, the intensity normalization by the pons provided at least 1.7- and 2.5-fold more significant cluster volumes than other normalizations for conventional and digital PET, respectively. CONCLUSIONS: The pons is the most appropriate area for brain 18FDG PET intensity normalization for examining the metabolic changes through ageing.

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer.

In this study, poly (lactic-co-glycolic) acid nanoparticles loading inorganic molybdenum octahedral cluster were used for photodynamic therapy (PDT) of ovarian cancer. Three cluster compounds, ((C4H9)4N)2[{Mo6Br8}Br6], Cs2[{Mo6Br8}Br6] and Cs2[{Mo6I8}(OOC2F5)6] denoted TMB, CMB and CMIF were studied following their incorporation in nanoparticles by a nanoprecipitation method. All resulting nanoparticles exhibited physico-chemical characteristics such as size and zeta potential compatible with cellular uptake. All cluster compounds tested were shown to produce singlet oxygen in vitro once released from their nanoparticulate system. Confocal images showed an internalisation of cluster loaded nanoparticles (CNPs) in A2780 ovarian cancer cell line, more efficient with CMIF compared to CMB or TMB loaded nanoparticles. In vitro cellular viability studies conducted on A2780 cell line treated with non activated CNPs did not show any sign of toxicity for concentrations up to 15 µM. Following photo-activation, CNPs were able to generate singlet oxygen resulting in a decrease of the cellular viability, compared to non-activated conditions. Nevertheless, no significant differences between IC50 with or without photo-activation were observed with TMB and CMB CNPs while for CMIF loaded nanoparticles, the photo-activation led to a significant decrease of cellular viability compared to the non activated condition and this decrease was independant of the P/C ratio. The strong photo-toxicity obtained for CMIF loaded nanoparticles with a P/C ratio of 2.5, as shown with half maximal inhibitory concentration (IC50) value near 1.8 µM suggests that PLGA nanoparticles seem to be efficient delivery systems intended for tumor management and that CMIF can be further investigated as photosensitizer for PDT of ovarian cancer.

From molecules to nanovectors: Current state of the art and applications of photosensitizers in photodynamic therapy.

Photodynamic therapy (PDT) is a concept based on a selective activation by light of drugs called photosensitizers (PS) leading to reactive oxygen species production responsible for cell destruction. Mechanisms of photodynamic reaction and cell photo-destruction following direct or indirect mechanisms will be presented as well as PS classification, from first generation molecules developed in the 1960 s to third generation vectorized PS with improved affinity for tumor cells. Many clinical applications in dermatology, ophthalmology, urology, gastroenterology, gynecology, neurosurgery and pneumology reported encouraging results in human tumor management. However, this interesting technique needs improvements that are currently investigated in the field of PS excitation by the design of new PS intended for two-photon excitation or for X-ray excitation. The former excitation technique is allowing better light penetration and preservation of healthy tissues while the latter is combining PDT and radiotherapy so that external light sources are no longer needed to generate the photodynamic effect. Nanotechnology can also improve the PS to reach the tumor cells by grafting addressing molecule and by increasing its aqueous solubility and consequently its bioavailability by encapsulation in synthetic or biogenic nanovector systems, ensuring good drug protection and targeting. Co-internalization of PS with magnetic nanoparticles in multifunctional vectors or stealth nanoplatforms allows a theranostic anticancer approach. Finally, a new category of inorganic PS will be presented with promising results on cancer cell destruction.

[Polymyalgia rheumatic and chronic myelomonocytic leukemia]. / Pseudo-polyarthrite rhizomélique satellite d'une leucémie myélomonocytaire chronique.

INTRODUCTION: Myelodysplasia (MDS) can occur as systemic manifestations such as connective tissue diseases or vasculitis. Rheumatological manifestations are also described in such context. Herein, we report the observation of a patient with chronic myelomonocytic leukemia (CMML) who developed systemic manifestations: polymyalgia rheumatica and pericarditis. CASE REPORT: A 78-year-old patient was referred for the exploration of two months history of inflammatory shoulder pain associated with biological inflammatory syndrome. He presented with asthenia, anorexia and loss of 5kg in one month. He had a three years follow-up for a CMML without any specific treatment. All of the explorations carried out showed a typical polymyalgia rheumatica. A pericardial effusion requiring emergency drainage was synchronously diagnosed. All the symptoms occurred during a worsening of his hematological disease. The rheumatological manifestation was favorable after a short corticosteroid therapy and pericarditis did not recur after 2 years of follow-up. CONCLUSION: It should be necessary to screen patients for MDS in a context of systemic manifestation, especially in elderly patients with an abnormal blood count (cytopenia, macrocytosis and monocytosis).

[Lung involvement of pyoderma gangrenosum: Diagnostic and therapeutic discussion based on a case report and a targeted literature review]. / Atteinte pulmonaire de pyoderma gangrenosum : discussion diagnostique et thérapeutique à partir d'un cas et d'une revue ciblée de la littérature.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, mainly dermatological condition, whose unusual and little-known lung involvement presents a diagnostic and therapeutic challenge. CASE REPORT: A 66-year-old man, followed for 6 years for an IgA monoclonal gammopathy of undetermined significance and an initially cutaneous corticosteroid-dependent PG, received a pneumonectomy for a mass suspected of neoplasia, that turns out to be a PG pulmonary localisation. During successive pneumopathies, sometimes dyspneic and excavated, several hypotheses are discussed. Various infectious and immunological explorations, and various antibacterial/fungal or immunosuppressive therapies are conducted, to finally conclude to pulmonary and/or cutaneous recurrences of PG. The outcome at 14 months seems finally favourable with tofacitinib. CONCLUSION: The recognition of cutaneous involvement of PG, which is essential for the diagnosis of its lung involvement, is probably the mirror of its evolution under treatment. Only multidisciplinary confrontation of reported cases will allow the elaboration of diagnostic and therapeutic recommendations.

Belgian and European experience with the European Homograft Bank (EHB) cryopreserved allograft valves.--assessment of a 20 year activity.

European Homograft Bank (EHB) has been selecting, preparing, storing and distributing the cryopreserved allograft valves in Belgium and some other European Countries since 1989. It was established in 1988 by a pathologist and the cardiac and vascular surgeons from Belgian and other European centres as an inter-university, international nonprofit association. Due to its neutral behavior and very high quality criteria, European Homograft Bank became one of the prominent heart valve banks in Europe and wider. It collaborates with the transplant coordination in donor selection as well as with the huge network of the implanting surgeons in Belgium and other European Countries. The EHB responsible discusses with the implanting surgeon the allograft selection on basis of the indication and the patients state of emergency. A total of 8.911 donor heart valves have been evaluated in EHB during the last 20 years. After selection, 5.258 allograft valves (1.996 aortic, 3.189 pulmonary and 73 mitral) were cryopreserved and stored in vapors of liquid nitrogen between 6 weeks and 5 years. A total of 4.516 allograft valves (1.391 aortic, 2.620 pulmonary and 48 mitral) were implanted in the left or right ventricular outflow tract for replacement of the diseased aortic or pulmonary valve and for mitral or tricuspid valve replacement or repair. In 1.380 cases the allograft valves were used for right ventricular outflow tract reconstruction as part of the Ross- procedure, whereas in 668 cases the allograft valve served for replacement of the aortic valve for endocarditis. The most important indications for use of cryopreserved allograft valves were: important cardiac and valve malformation in children, female patients of child-bearing age with diseased cardiac valves, cases with contra-indication for anti-coagulation and the patients with severe endocarditis with septal or annular abscesses. Although the number of the donation increased by year, the available allograft valves in stock are still insufficient to respond to all the surgeons' request for different indications.

Involvement of the cerebellum in EMDR efficiency: a metabolic connectivity PET study in PTSD.

BACKGROUND: We recently reported an improvement of precuneus PET metabolism after EMDR therapy in military participants suffering from PTSD. OBJECTIVE: The aim of the present study was to investigate the metabolic changes of precuneus connectivity in these participants after such treatment. METHOD: Fifteen participants with PTSD performed a brain 18F-FDG-PET sensitized by virtual reality exposure to war scenes, before and after EMDR treatment. Inter-regional correlation analysis was performed to study metabolic changes of precuneus connectivity through SPMT maps at whole-brain level (p < 0.005 for the voxel, p < 0.05 for the cluster). RESULTS: A decrease of connectivity was observed after EMDR between the precuneus and two significant bilateral clusters of the cerebellum (bilateral Crus I and VI cerebellar lobules, Tmax voxel of 5.8 and 5.3, and cluster size of 343 and 314 voxels, respectively). Moreover, higher cerebellar metabolism before treatment was associated with reduced clinical PTSD scores after EMDR (p = 0.03). CONCLUSIONS: The posterior cerebellum and its metabolic connectivity with the precuneus are involved in the clinical efficiency of EMDR in PTSD.

Antecedentes: Recientemente informamos una mejora del metabolismo de PET precuneus después de la terapia EMDR en participantes militares que padecen TEPT.Objetivo: El objetivo del presente estudio fue investigar los cambios metabólicos en la conectividad precuneus en estos participantes después de dicho tratamiento.Métodos: Quince participantes con trastorno de estrés postraumático se sometieron a 18F-FDG-PET cerebral sensibilizado por la exposición de realidad virtual a escenas de guerra antes y después del tratamiento con EMDR. El análisis de correlación interregional se realizó para estudiar los cambios metabólicos en la conectividad precuneus a través de mapas SPM-T a nivel de todo el cerebro (p <0.005 para el vóxel, p <0.05 para el grupo).Resultados: Se observó una disminución en la conectividad después de la terapia EMDR entre el precúneo y dos grupos bilaterales significativos del cerebelo (vóxeles Tmax de 5.8 y 5.3 y tamaños de racimo de 343 y 314 vóxeles, respectivamente). Además, un metabolismo cerebeloso más alto antes del tratamiento se asoció con puntuaciones clínicas de TEPT reducidas después de EMDR (p = 0.03).Conclusión: el cerebelo y su conectividad metabólica con el precuneus están involucrados en la eficiencia clínica de EMDR en TEPT.