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Rethinking de novo immune hepatitis,an old concept for liver allograft rejection:relevance of glutathione S-transferase T1 mismatch

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World Journal of Gastroenterology 2018年第29期24卷 3239-3249页

作者： Isabel Aguilera Elena aguado-Dominguez jose Manuel Sousa Antonio Nunez-Roldan Department of Immunology Instituto de Biomedicina de Sevilla(IBIS)Hospital Universitario Virgen del RocíoSevilla 41013Spain Digestive and Liver Diseases Service Hospital Universitario Virgen del RocíoSevilla 41013Spain

Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis(dn AIH) when studied. In its latest update, the Banff Working Group for liver allograft pathology proposed replacing the term dn AIH with plasma cell(PC)-rich rejection. Antibodies to glutathione S-transferase T1(GSTT1) in null recipients of GSTT1 positive donors have been included as a contributory but nonessential feature of the diagnosis of PC-rich rejection. Also in this update, non-organ-specific anti-nuclear or smooth muscle autoantibodies are no longer included as diagnostic criteria. Although initially found in a proportion of patients with PC-rich rejection, the presence of autoantibodies is misleading since they are not diseasespecific and appear in many different contexts as bystanders. The cellular types and proportions of the inflammatory infiltrates in diagnostic biopsies have been studied in detail very recently. PC-rich rejection biopsies present a characteristic cellular profile with a predominance of T lymphocytes and a high proportion of PCs, close to 30%, of which 16.48% are Ig G4+. New data on the relevance of GSTT1-specific T lymphocytes to PC-rich rejection will be discussed in this review.

关键词： glutathione S-transferase T1 mismatch liver allograft rejection plasma cell-rich rejection de novo autoimmune hepatitis donor-specific antibodies newCAST cell quantification IgG4+plasma cell T lymphocytes

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation

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World Journal of Gastroenterology 2019年第26期25卷 3291-3298页

作者： jose Tiago Silva Rafael San-Juan Mario Fernández-Ruiz José María aguado Unit of Infectious Diseases Hospital Universitario "12 de Octubre" Instituto de Investigación Hospital "12 de Octubre" (imas12) School of Medicine Universidad Complutense

Solid organ transplantation(SOT)is the best treatment option for end-stage organ *** immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium *** tuberculosis(TB)after SOT is a significant cause of morbidity and *** cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive *** minimization strategies have been developed to diagnose LTBI and initiate treatment prior to *** with vitamin B6 supplementation is the treatment of ***,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT ***(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than *** the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

关键词： Fluoroquinolones Mycobacterium tuberculosis Latent tuberculosis infection Liver transplantation Drug-induced liver graft injury

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

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Regenerative Biomaterials 2019年第6期6卷 335-347页

作者： Filippo Cipriani Blanca Arino Palao Israel Gonzalez de Torre Aurelio Vega Castrillo Hector jose aguado Hernandez Matilde Alonso Rodrigo Angel jose Alvarez Barcia Ana Sanchez Veronica Garcıa Diaz Monica Lopez Pena jose Carlos Rodriguez-Cabello Technical Proteins Nanobiotechnology S.L. Paseo Belen 9AValladolid 47011Spain Departamento de traumatologıa Hospital Clınico de ValladolidAv.Ramon y Cajal 3Valladolid 47003Spain Bioforge University of Valladolid CIBER-BBNPaseo de Belen 19Valladolid 47011Spain SIBA-UVA:servicio investigacion y bienestar animal University of ValladolidC/Plaza de Santa Cruz 8Valladolid 47002Spain Instituto de Biologıa y Genetica Molecular(IBGM) Universidad de Valladolid y CSICCalle Sanz y Fores 3Valladolid 47003Spain Facultad de veterinaria Campus UniversitarioAvda.Carballo Calero s/nLugo 27002Spain

The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral *** the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand ***,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the *** both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline *** conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

关键词： biopolymer animal test cartilage bone

Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

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World Journal of Clinical Oncology 2022年第5期13卷 314-322页

作者： Carlos aguado Luis Chara Mónica Antonanzas jose maria Matilla Gonzalez Unai Jiménez Raul Hernanz Xabier Mielgo-Rubio Juan Carlos Trujillo-Reyes Felipe Counago Department of Medical Oncology Hospital Clínico Universitario San CarlosMadrid 28040Spain Department of Medical Oncology Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Thoracic Surgery Hospital Clínico Universitario de ValladolidValladolid 47005Spain Department of Thoracic Surgery Hospital Universitario CrucesBarakaldoBizkaia 48903Basque CountrySpain Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Medical Oncology Hospital Universitario Fundación AlcorcónAlcorcón 28922MadridSpain Department of Thoracic Surgery Hospital de la Santa Creu I Sant PauBarcelona 08029CataloniaSpain Department of Surgery Universitat Autonoma de BarcelonaBarcelona 08029CataloniaSpain Department of Radiation Oncology Hospital Universitario Quirónsalud MadridPozuelo de Alarcón 28223MadridSpain Department of Radiation Oncology Hospital La LuzMadrid 28003Spain Medicine Department School of Biomedical SciencesUniversidad Europea de MadridVillaviciosa de Odón 28670MadridSpain

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical *** chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable *** with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional *** immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term ***,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative ***,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival *** we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

关键词： Non-small cell lung cancer Neoadjuvant Immune checkpoint inhibitors Immunotherapy Anti-PD1 Anti-PD-L1 Complete pathological response

A Comparative Study on Efficacy of Fludrocortisones versus Glucocorticoids and Vasodilators in the Treatment of Idiopathic Sensorineural Cochlear Hearing Loss

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International Journal of Otolaryngology and Head & Neck Surgery 2015年第2期4卷 115-123页

作者： Daniel López-Campos Daniel López-aguado Eugenia M.Campos-Banales jose Luis de Serdio-Arias Mar García-Sáinz ENT Service University Hospital of the Canary IslandsTenerifeSpain Department of Otorhinolaryngology La Laguna UniversityTenerifeSpain ENT Service University Hospital Nuestra Senora de CandelariaTenerifeSpain Pharmacology and Pharmacotherapy Service University Hospital of the Canary IslandsTenerifeSpain

Introduction and Objectives: The idiopathic sensorineural cochlear hearing loss is one of the most frequent human sensory deficits and there is no specific drug therapy for it. The possible hearing recovery is related with the reestablishment of normal ionic homeostasis of the endolymph controlled by the mineralocorticoid as could be demonstrate experimentally. The purpose of this clinical trial was to confirm the efficacy of mineralocorticoids to the recovery of hearing level in patients suffering idiopathic sensorineural hearing loss (SNHL) against the glucocorticoids and vasodilator drugs. Material and Methods: The research lasted three months and involved 90 patients allocated into four different groups: Placebo group, consisted of 20 patients (10 men and 10 women);the group consisting of 22 patients treated with glucocorticoid therapy (12 men and 10 female);the group treated with mineralocorticoid therapy encompassed 26 patients (13 males and 13 females) and the group of vasodilators formed by 22 patients (12 men and 10 women). The level of hearing loss was estimated by the tests Liminal Tone Audiometry (LTA) and Auditory Brainstem Response (ABR). Results: The main features in this research were overall better response in improving the hearing level with the mineralocorticoid therapy. This improvement in hearing levels was greater in women than in men, and a higher response was found in the left ear regardless of patient’s gender. Conclusions: The hearing gain was significantly superior in the mineralocorticoids group followed by the glucocorticoids group whereas the response to vasodilators was lesser and with no statistical significance.

关键词： Idiopathic Sensorineural Cochlear Hearing Loss(ISNCHL) Liminal Tonal Audiometry(LTA) Auditory Brainstem Response(ABR)