Efficacy of a transdiagnostic internet-based program for adolescents with emotional disorders: A randomized controlled trial.

OBJECTIVE: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) is a well-established transdiagnostic cognitive-behavioral therapy (T-CBT) intervention. The aim of the present study was to examine the efficacy of the program Learn to Manage your Emotions [Aprende a Manejar tus Emociones] (AMtE), a self-applied transdiagnostic internet-delivered program based on the Spanish version of the UP-A. This is the first transdiagnostic internet-based program designed for the treatment of emotional disorders in adolescents. METHOD: A sample of Spanish adolescents with a primary diagnosis of an anxiety and/or depressive disorder (n = 58; age range = 12-18 years; 78.3% girls; 90% Caucasian) were randomly allocated to receive AMtE (n = 28) or the UP-A via videocall (n = 30). Pre-treatment, post-treatment and 3-month follow-up data were collected using self-reports and clinician-rated measures of anxiety, depression, positive and negative affect, anxiety sensitivity and emotional avoidance. RESULTS: Based on generalized estimating equations (GEE) models, both intervention programs were effective in significantly reducing self-reported anxiety and depressive disorder symptoms and clinician-rated severity of anxiety and depression, as well as self-reported transdiagnostic outcome variables. CONCLUSIONS: Data provide empirical support for the efficacy of AMtE as a transdiagnostic online CBT treatment for anxiety and depressive disorders in adolescents. No marked nor consistent differences were observed between the UP-A and AMtE, highlighting the potential usefulness of the online self-administered AMtE program.

CD19-immunoPET for noninvasive visualization of CD19 expression in B-cell lymphoma patients.

Cell- and antibody-based CD19-directed therapies have demonstrated great potential for treating B-cell non-Hodgkin lymphoma (B-NHL). However, all these approaches suffer from limited response rates and considerable toxicity. Until now, therapy decisions have been routinely based on histopathological CD19 staining of a single lesion at initial diagnosis or relapse, disregarding heterogeneity and temporal alterations in antigen expression. To visualize in vivo CD19 expression noninvasively, we radiolabeled anti-human CD19 monoclonal antibodies with copper-64 (64Cu-αCD19) for positron emission tomography (CD19-immunoPET). 64Cu-αCD19 specifically bound to subcutaneous Daudi xenograft mouse models in vivo. Importantly, 64Cu-αCD19 did not affect the anti-lymphoma cytotoxicity of CD19 CAR-T cells in vitro. Following our preclinical validation, 64Cu-αCD19 was injected into four patients with follicular lymphoma, diffuse large B-cell lymphoma or mantle zone lymphoma. We observed varying 64Cu-αCD19 PET uptake patterns at different lymphoma sites, both within and among patients, correlating with ex vivo immunohistochemical CD19 expression. Moreover, one patient exhibited enhanced uptake in the spleen compared to that in patients with prior B-cell-depleting therapy, indicating that 64Cu-αCD19 is applicable for identifying B-cell-rich organs. In conclusion, we demonstrated the specific targeting and visualization of CD19+ B-NHL in mice and humans by CD19-immunoPET. The intra- and interindividual heterogeneous 64Cu-αCD19 uptake patterns of lymphoma lesions indicate variability in CD19 expression, suggesting the potential of CD19-immunoPET as a novel tool to guide CD19-directed therapies.

Association of Neurofilament Light Chain, [18F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With ß-Amyloid-Negative CBS.

BACKGROUND AND OBJECTIVES: Corticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in ß-amyloid (Aß)-negative CBS. METHODS: We included patients with clinically diagnosed Aß-negative CBS with clinical follow-up data who underwent baseline structural MRI and plasma-NfL analysis for assessing neurodegeneration, [18F]PI-2620-PET for assessing tau pathology, [18F]GE-180-PET for assessing microglia activation, and plasma-GFAP analysis for assessing astrocytosis. To quantify tau and microglia load, we assessed summary scores of whole-brain, cortical, and subcortical PET signal. For structural MRI analysis, we quantified subcortical and cortical gray matter volume. Plasma NfL and GFAP values were assessed using Simoa-based immunoassays. Symptom progression was determined using a battery of cognitive and motor tests (i.e., Progressive Supranuclear Palsy Rating Scale [PSPRS]). Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster symptom progression over time (i.e., time × biomarker interaction). RESULTS: Overall, 21 patients with Aß-negative CBS with ∼2-year clinical follow-up data were included. Patients with CBS with more widespread global tau-PET signal showed faster clinical progression (PSPRS: B/SE = 0.001/0.0005, p = 0.025), driven by cortical rather than subcortical tau-PET. By contrast, patients with higher global [18F]GE-180-PET readouts showed slower clinical progression (PSPRS: B/SE = -0.056/0.023, p = 0.019). No association was found between gray matter volume and clinical progression. Concerning fluid biomarkers, only higher plasma-NfL (PSPRS: B/SE = 0.176/0.046, p < 0.001) but not GFAP was associated with faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau-PET, TSPO-PET, and plasma-NfL showed significant interaction effects with time on clinical trajectories when tested in the same model. DISCUSSION: [18F]PI-2620 tau-PET, [18F]GE-180 TSPO-PET, and plasma-NfL show prognostic potential for clinical progression in patients with Aß-negative CBS with probable 4-repeat tauopathy, which can be useful for clinical decision-making and stratifying patients in clinical trials.

LESS ovariohysterectomy in cats using a new homemade multiport / Ovário-histerectomia por LESS em gatas com um novo multiportal artesanal

ABSTRACT: The purpose of this study was to assess the use of a homemade multiport for LESS (laparoendoscopic single-site surgery) ovariohysterectomy (OVH) in cats. Intra and postoperative variables of the surgery steps, technical challenges, complications and evolution of surgical time by a surgeon in training were evaluated. Twenty queens were selected for LESS OVH. The multiport device was manufactured of a conical-shaped ethylene polytereftalate (PET) bottle, urethral catheter no. 8, latex balloon no. 11, a 3.5mm and a 6mm laparoscopic trocars. Hemostasis was carried out using bipolar diathermy. Mean total surgical time was 14.54±5.12 minutes. Approach to right and left ovarian pedicles and abdominal access for insertion of the multiport device were the most time consuming surgical steps. LESS ovariohysterectomy using a new homemade multiport device is feasible and safe. Thus, the proposed technique may be considered as a minimally invasive alternative to ovariohysterectomy in the feline specie.

RESUMO: Objetivou-se avaliar o emprego do novo dispositivo multiportal artesanal para realização de ovariohisterectomia por LESS (cirurgia laparoendoscópica por único acesso) em gatas, analisando variáveis intraoperatórias de tempo cirúrgico das diferentes etapas que compõem o procedimento, suas possíveis dificuldades técnicas de execução e complicações trans e pós-operatórias. Avaliou-se ainda a curva de aprendizado deste procedimento, realizado por um cirurgião não proficiente na técnica. Vinte gatas foram submetidas à laparoscopia. Para a confecção do multiportal foi utilizado um recipiente de politereftalato de etileno (PET), uma sonda uretral nº8, um balão de látex nº11, um portal de videocirurgia de 3,5mm, e um de 6mm. O sistema de coagulação foi o bipolar. O tempo cirúrgico médio foi de 14,54±5,12 minutos. A abordagem aos pedículos ovarianos direito e esquerdo e o acesso para introdução do portal foram as etapas que apresentaram maior tempo de execução. A OVH videoassistida empregando o novo dispositivo multiportal é factível, não demonstrando complicações. Acredita-se, portanto, que a técnica proposta torna-se uma alternativa para realização minimamente invasiva de ovariohisterectomia em felinos.