Repositorio Institucional Fleni
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HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy
Full text linkCancer immunotherapies based mainly on the blockade of immune-checkpoint (IC)
molecules by anti-IC antibodies offer new alternatives for treatment in oncological
diseases. However, a considerable proportion of patients remain unresponsive to them.
Hence, the development of novel clinical immunotherapeutic approaches and/or
targets are crucial. In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4
has caused great interest since it is abnormally expressed in several malignancies
generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to
block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal
cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids
targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLAG was reached to different degrees, including complete silencing. Most importantly,
HLA-G – cells triggered a higher in vitro response of immune cells with respect to HLA-G
+ wild type cells. Altogether, we demonstrated for the first time the HLA-G
downregulation through gene editing. We propose this approach as a first step to
develop novel clinical immunotherapeutic approaches in cancer.Fil: Palma, María Belén. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Cátedra de Citología, Histología y Embriología; Argentina. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Tronik-Le Roux, Diana. Saint-Louis Hospital; Francia. Université de Paris; Francia.Fil: Amín, Guadalupe. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Castañeda, Sheila. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Möbbs, Alan M. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Scarafia, María Agustina. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: La Greca, Alejandro. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina.Fil: Daouya, Marina. Saint-Louis Hospital; Francia. Université de Paris; Francia.Fil: Poras, Isabelle. Saint-Louis Hospital; Francia. Université de Paris; Francia.Fil: Inda, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Cátedra de Citología, Histología y Embriología; Argentina. Comisión de Investigaciones Científicas; Argentina.Fil: Moro, Lucía Natalia. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Carosella, Edgardo D. Saint-Louis Hospital; Francia. Université de Paris; Francia.Fil: García, Marcela N. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Cátedra de Citología, Histología y Embriología; Argentina.Fil: Miriuka, Santiago G. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Cátedra de Citología, Histología y Embriología; Argentina. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Terson syndrome caused by intraventricular hemorrhage associated with arteriovenous malformation: Case report
No full textFil: Villamil, Facundo. Fleni. Departamento de Neurocirugía; Argentina.Fil: Pastor Rueda, Juan Manuel. Fleni. Departamento de Neurocirugía; Argentina.Fil: Giovannini, Sebastián. Fleni. Departamento de Neurocirugía; Argentina.Fil: Ries Centeno, Tomás. Fleni. Departamento de Neurocirugía; Argentina.Fil: Marco Del Pont, Francisco. Fleni. Departamento de Neurocirugía; Argentina.Fil: Millar Vernetti, Patricio. Fleni. Departamento de Neurocirugía; Argentina.Fil: Condomí Alcorta, Santiago G. Fleni. Departamento de Neurocirugía; Argentina
Dyskeratosis congenita and a rare brain abscess
No full textDyskeratosis congenita is a rare inheritable disease which causes peculiar dermatological features
and bone marrow failure with an increased risk of severe infections and neoplasia. Actinomyces
spp. is part of the oral cavity flora. Invasive infections are mostly seen in immunocompromised hosts. We report
a case of a rare central nervous infection and an underling inheritable disease.Fil: Blaquier, Juan Bautista. Fleni. Departamento de Medicina Interna; Argentina.Fil: Castiglione, Juan Ignacio. Fleni. Departamento de Neurología; Argentina.Fil: Delorme, Ricardo. Fleni. Departamento de Medicina Interna; Argentina.Fil: Wainsztein, Néstor Adrián. Fleni. Departamento de Medicina Interna; Argentina
Social Cognition In Early Multiple Sclerosis: Neuropsychological And Anatomical Approach
No full textCognitive impairment and deficits in social cognition (SC) are frequent in patients with multiple sclerosis (MS). The aim of the present work is to study SC in patients with early MS and to analyze its neuroanatomical correlation. Thirty-four patients with relapsing remitting MS, with ≤ 2 years of disease progression and EDSS and ≤2, and 30 healthy control subjects matched for age, sex, and educational level were recruited. Subjects performed a comprehensive neuropsychological assessment (Rao BRB). SC was assessed using the International Affective Picture System IAPS, The Eyes in the Mind Test, the Empathy Quotient, and the Faux Pas Test. The anatomical correlation of patients with deficits in social cognition was studied through brain MRI and voxel-based morphometric for which cortical reconstruction and volumetric segmentation were performed using Freesurfer processing software. Patients showed significant deficits in executive functions, verbal memory and language tests. SC assessment showed that patients presented greater difficulties in the Faux Pas Test (p = 0.023), The Mind in the Eyes Test (p = 0.014), and presented a positive bias in the interpretation of neutral images of the IAPS (P = 0.023). Furthermore, patients with CS deficits presented less cortical thickness in areas of the right supramarginal gyrus, pars opercularis, and anterior cingulum.Fil: Crivelli, Lucía. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Calandri, Ismael Luis. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Helou, María Belen. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Keller, Greta. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Fiol, Marcela Paula. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Ysrraelit, María Célica. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Gaitan, María Inés. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina
Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool
No full textObjective
To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug‐resistant epilepsy.
Methods
We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques.
Results
Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow‐up = 24 months), and 1050 of 1237 (85%) were seizure‐free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18‐fluoro‐2‐deoxyglucose–positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.
Significance
Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision‐making.Fil: Weil, Alexander G. Saint Justine University Hospital Centre; Canada.Fil: Lewis, Evan C. Neurology Centre of Toronto; Canada.Fil: Ibrahim, George M. University of Toronto; Canada.Fil: Kola, Olivia. David Geffen School of Medicine at University of California; Estados Unidos.Fil: Tseng, Chi-Hong. David Geffen School of Medicine at University of California; Estados Unidos.Fil: Zhou, Xinkai. University of California; Estados Unidos.Fil: Lin, Kao-Min. Xiamen Humanity Hospital; China.Fil: Cai, Li-Xin. Peking University First Hospital; China.Fil: Liu, Qing-Zhu. Tsinghua University; China.Fil: Lin, Jiu-Luan. Tsinghua University; China.Fil: Zhou, Wen-Jing. Tsinghua University; China.Fil: Mathern, Gary W. David Geffen School of Medicine at University of California; Estados Unidos.Fil: Smyth, Matthew D. St. Louis Children's Hospital; Estados Unidos.Fil: O'Neill, Brent R. Children's Hospital Colorado; Estados Unidos.Fil: Dudley, Roy. Montreal Children's Hospital; Canadá.Fil: Ragheb, John. Nicklaus Children's Hospital; Estados Unidos.Fil: Bhatia, Sanjiv. Nicklaus Children's Hospital; Estados Unidos.Fil: Pociecha, Juan. Fleni. Centro Integral de Epilepsia y Unidad de Monitoreo de Videoelectroencefalografía; Argentina.Fil: Chamorro, Noelia. Fleni. Centro Integral de Epilepsia y Unidad de Monitoreo de Videoelectroencefalografía; Argentina.Fil: Muro, Valeria L. Fleni. Centro Integral de Epilepsia y Unidad de Monitoreo de Videoelectroencefalografía; Argentina
Editorial: Immunosuppressive Amino Acid Catabolizing Enzymes in Heallth and Disease
No full textResumen no disponibleFil: Castellano, Flavia. Université Paris-Est Créteil; Francia. Hopital Henri Mondor; Francia.Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Molinier-Frenkel, Valerie. Université Paris-Est Créteil; Francia. Hopital Henri Mondor; Francia
The impact of hydroxychloroquine on obstetric outcomes in refractory obstetric antiphospholipid syndrome
No full textBackground: The use of low-dose aspirin (LDA) and heparin has improved pregnancy outcomes in women with antiphospholipid syndrome (APS). However, 20-30% still have adverse outcomes despite treatment. Recent retrospective studies showed a beneficial effect of hydroxychloroquine (HCQ) in APS due to its anti-inflammatory, immunomodulatory and antithrombotic properties. Data in refractory obstetric APS (OAPS) remain scarce and include heterogeneous populations with various concomitant treatments.
Objective: The objective of this study was to assess the impact on the obstetric outcomes of adding HCQ to classical treatments for women with refractory primary obstetric APS.
Methods: In a retrospective single-centre cohort study, we compared pregnancy outcomes in women with refractory primary OAPS (2004-2019) who received two different treatments in subsequent pregnancies. Group A received 400 mg HCQ + 60 mg enoxaparin + LDA, while Group B received 60 mg enoxaparin + LDA. The main outcome was live birth rates, while pregnancy complications (early and late pregnancy losses and placental-mediated complications) were the secondary outcome.
Results: A total of 101 pregnancies in 87 refractory primary OAPS patients were included. The rate of live-born babies in Group A (HCQ) was 97.1% (67/69) vs. 62.5% (20/32) in Group B (RR: 1.55 [95% CI, 1.19-2.1]; p < 0.001). Pregnancy complications in Group A were 8.7% (6/69) vs. 37.5% (12/32) in Group B (RR 0.22 [95% CI, 0.15-0.30]; p < 0.001).
Conclusion: Hydroxychloroquine was associated with a higher rate of live births and a lower prevalence of pregnancy complications in refractory primary obstetric APS. The addition of HCQ to classical treatment may present a promising approach that needs to be confirmed with prospective studies.Fil: Gerde, M. Hospital Universitario Austral; Argentina.Fil: Ibarra, E. Hospital Universitario Austral; Argentina.Fil: Mac Kenzie, Ronaldo. Fleni. Servicio de Cardiología; Argentina.Fil: Fernandez Suarez, C. Hospital Universitario Austral; Argentina.Fil: Heer, C. Hospital Universitario Austral; Argentina.Fil: Alvarez, R. Hospital Universitario Austral; Argentina.Fil: Iglesias, M. Hospital Universitario Austral; Argentina.Fil: Balparda, J. Hospital Universitario Austral; Argentina.Fil: Beruti, E. Hospital Universitario Austral; Argentina.Fil: Rubinstein, F. Instituto de Efectividad Clínica y Sanitaria; Argentina
Abstract P84: Covid-19 and Stroke in the Latin American Stroke Registry (LASE)
No full textBackground: Ischemic stroke has been reported to occur in approximately 5% of COVID-19 patients, although some reports are contradictory. Proposed mechanisms of this association are hypercoagulable state, vasculitis and cardiomyopathy, together with traditional vascular risk factors. We analyzed the frequency and clinical characteristics of COVID-19 positive stroke cases during the first months of the pandemic in Latin America.
Methods: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March - June 2020). We assessed acute stroke cases associated to COVID-19 infection. Clinical characteristics, stroke etiology and severity, acute care and functional outcomes, were compared between non-COVID-19 and COVID-19 cases.
Results: There were a total of 1037 stroke cases; sixty-two of them (6.0%) were diagnosed with COVID-19 infection. This group consisted of 38 men [61.3%], with a median age of 68 years [IQR 59-79 years]. From these cases, 80.6% were ischemic stroke, 16.1% hemorrhagic stroke, and 1.6% transient ischemic attack and cerebral venous thrombosis respectively. The most common etiology reported for ischemic cases was atherosclerotic large vessel occlusion (30.6% vs. 12.7% in non-COVID cases, p<0.001), and undetermined etiology for hemorrhagic stroke (55.6%). Median NIHSS for COVID-stroke patients was higher (7 IQR 2-16 vs. 5 IQR 2-11, p=0.05). Five (8.1%) patients received acute reperfusion therapy, with no differences in door-to-CT, door-to-needle and door-to-groin times, compared to non-COVID cases. Most characteristics did not differ from those of COVID-19 negative patients. Mortality was higher in COVID-stroke cases (20.9% vs. 9.6%, p<0.001).
Conclusions: COVID-19 infection frequency in stroke patients in Latin America is similar to that reported in several series worldwide, with a higher frequency of atherosclerotic ischemic strokes and mortality compared to non COVID-19 strokes.Fil: Pujol Lereis, Virginia Andrea. Fleni. Centro Integral de Neurología Vascular; Argentina.Fil: Flores, Alan. Hosp Joan XXIII; España.Fil: Arauz-Gongora, Antonio. Instituto Nacional de Neurologia; México.Fil: Abanto-Argomedo, Carlos. Instituto Nacional de Ciencias Neurológicas; Perú.Fil: Amaya, Pablo. Fundación Clínica Valle del Lili; Colombia.Fil: Bayona, Hernán. Hospital Universitario Fundación Santa Fe de Bogotá; Colombia.Fil: Bonardo, Pablo. Hospital Británico de Buenos Aires; Argentina.Fil: Diaz-Escobar, Luis. Hospital de Clínicas; Paraguay.Fil: Gomez Schneider, Maia Macarena. Sanatorio de los Arcos; Argentina.Fil: Góngora-Rivera, Fernando. Hospital Universitario José Eleuterio González; México.Fil: Lavados, Pablo M. Clínica Alemana de Santiago; Chile.Fil: León, Carolina. ISSSTE; México.Fil: Luraschi, Adriana. Hospital Pirovano; Argentina.Fil: Márquez-Romero, Juan Manuel. Instituto Mexicano del Seguro Social; México.Fil: Martins, Sheila C. Hospital de Clínicas de Porto Alegre; Brasil.Fil: Navia, Victor Hugo. Hospital Padre Hurtado; Chile.Fil: Ruiz-Franco, Angelica. Hospital Juárez; México.Fil: Vences, Miguel Angel. Hospital Nacional Edgardo Rebagliati Martins; Perú.Fil: Ameriso, Sebastián Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Vascular; Argentina
The quest for the identification of pathogenic patent foramen ovale
No full textResumen no disponibleFil: Ameriso, Sebastián Francisco. Fleni. Departamento de Neurología. Centro Integral de Neurología Vascular; Argentina
Vasculitic Peripheral Neuropathy, Differences Between Systemic and Non-Systemic Etiologies: A Case Series and Biopsy Report
No full textBackground:Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. Objective:This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. Methods:Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. Results:Twenty-five patients with VPN were included (SVN, n = 10; NSVN, n = 15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, p = 0.009). Erythrocyte sedimentation rate (ESR) values over 20 mm/h were significantly more common in SVN patients (100% vs. 60%, p = 0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; p = 0.03), with a higher proportion of definite VPN cases (92 vs 46%; p = 0.04). Conclusions:Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.Fil: Castiglione, Juan Ignacio. Fleni. Departamento de Neurología; Argentina.Fil: Marrodán, Mariano. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Alessandro, Lucas. Fleni. Departamento de Neurología; Argentina.Fil: Taratuto, Ana Lía. Fleni. Departamento de Neuropatología y Biología Molecular. Centro de Referencia Neuropatológico de Encefalopatías Espongiformes Transmisibles; Argentina.Fil: Brand, Patricio. Fleni. Departamento de Neurología. Servicio de Neurofisiología; Argentina.Fil: Nogués, Martín. Fleni. Departamento de Neurología; Argentina.Fil: Barroso, Fabio Adrián. Fleni. Departamento de Neurología. Sección de Enfermedades Neuromusculares; Argentina