Consensus document of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) and the Spanish Society of Anesthesiology and Resuscitation (SEDAR) on tracheotomy in patients with COVID-19 infection.

La alta incidencia de insuficiencia respiratoria aguda en el contexto de la pandemia por COVID-19ha conllevado el uso de ventilación mecánica hasta en un 15%. Dado que la traqueotomía es un procedimiento quirúrgico frecuente, este documento de consenso, elaborado por tres Sociedades Científicas, la SEMICYUC, la SEDAR y la SEORL-CCC, tiene como objetivo ofrecer una revisión de las indicaciones y contraindicaciones de traqueotomía, ya sea por punción o abierta, esclarecer las posibles ventajas y exponer las condiciones ideales en que deben realizarse y los pasos que considerar en su ejecución. Se abordan situaciones regladas y urgentes, así como los cuidados postoperatorios.post-print393 K

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study

[Background]: Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma.[Methods]: CARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18–75 years; with an Eastern Cooperative Oncology Group performance status of 0–2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 106 CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 106 CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 106 CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11.[Findings]: Between June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53–65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1–13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1–2). No cases of neurotoxic events were observed. Persistent grade 3–4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19.[Interpretation]: ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach.This work has been supported in part by grants from the Instituto de Salud Carlos III (cofunded by the EU), Spanish Ministry of Health (ICI19/00025, FIS PI18/00775, PI19/00669, and PI22/00647), complementary grant for CONCORD-023, RICORS-TERAV network (RD21/0017/0009 and RD21/0017/0019), Red de Terapia Celular TERCEL (RD16/0011/0005), Fondo Europeo de Desarrollo Regional (FEDER), 2017SGR00792 (AGAUR; Generalitat de Catalunya), Centro de Investigación Biomédica en Red de Cáncer CIBERONC (CB16/12/00369 and CB16/12/00489), La Caixa Foundation (CP042702/LCF/PR/GN18/50310007), Asociación Española Contra el Cancer (AECC) LABAE21971FERN, and Fundació Bosch I Aymerich support. AOC received funding from the resident grant Ajut Clínic-La Pedrera 2019, granted by Hospital Clínic de Barcelona.Peer reviewe

Carcinomas atípicos de la laringe. Descripción de dos casos

95% of the malignant neoplasm of the larynx are squamous carcinoma. Neuroendocrine carcinomas correspond to at least 1 % of laryngeal tumors. The supraglottic is the most frequent laryngeal localization. Diagnosis is based on histological and immunohistochemically characteristic. They are divided into four histological types, which have a different natural evolution and prognosis. Description: We present two cases of laryngeal neuroendocrine carcinomas. One of them belongs to a small cell neuroendocrine carcinoma and the other one to a large cell carcinoma, which diagnosis generated controversy.El 95% de las neoplasias malignas de laringe son de tipo carcinoma escamoso. Los carcinomas neuroendocrinos corresponden a menos del 1% de los tumores laríngeos. La localización laríngea más frecuente es la supraglotis. El diagnóstico se basa en las características histológicas e inmunohistoquímicas. Se dividen en cuatro tipos histológicos que tienen una evolución natural y pronóstico diferentes. Descripción: Exponemos dos casos de carcinomas neuroendocrinos de la laringe. Uno de ellos pertenece a la estirpe celular de carcinoma de células pequeñas y el otro a un carcinoma de células grandes, cuyo diagnóstico histológico generó controversias

Modification of Breast Cancer Milieu with Chemotherapy plus Dendritic Cell Vaccine: An Approach to Select Best Therapeutic Strategies

Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). This enrichment was seen in up to 67% of TNBC patients in the experimental arm as compared with the CG (20%). An association between CD8 TILs before NAC (4% cut-off point) and pathological complete response in the VG was found in the univariate and multivariate analysis (OR = 1.41, IC95% 1.05–1.90; p = 0.02, and OR = 2.0, IC95% 1.05–3.9; p = 0.03, respectively). Conclusion: Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC

Modification of Breast Cancer Milieu with Chemotherapy plus Dendritic Cell Vaccine: An Approach to Select Best Therapeutic Strategies

Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences (p = 0.11). This enrichment was seen in up to 67% of TNBC patients in the experimental arm as compared with the CG (20%). An association between CD8 TILs before NAC (4% cut-off point) and pathological complete response in the VG was found in the univariate and multivariate analysis (OR = 1.41, IC95% 1.05–1.90; p = 0.02, and OR = 2.0, IC95% 1.05–3.9; p = 0.03, respectively). Conclusion: Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC

Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies

Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and for the prevention of destructive immune responses after transplantation. The methodologies for generating tolAPC vary greatly between different laboratories, making it difficult to compare data from different studies; thus constituting a major hurdle for the development of standardised tolAPC therapeutic products. Here we describe an initiative by members of the tolAPC field to generate a minimum information model for tolAPC (MITAP), providing a reporting framework that will make differences and similarities between tolAPC products transparent. In this way, MITAP constitutes a first but important step towards the production of standardised and reproducible tolAPC for clinical application

Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies

Cellular therapies, with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and for the prevention of destructive immune responses after transplantation The methodologies for generating tolAPC vary greatly between different laboratories, making it difficult to compare data from different studies; thus constituting a major hurdle for the development of standardised tolAPC therapeutic products. Here we describe an initiative by members of the tolAPC field to generate a minimum information model for tolAPC (MITAP), providing a reporting framework that will make differences and similarities between tolAPC products transparent. In this way, MITAP constitutes a first but important step towards the production of standardised and reproducible tolAPC for clinical application.This work was supported by a grant from the European Cooperation in Science and Technology (COST) for the AFACTT project (Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies; BM1305). COST is part of the EU Framework Programme Horizon 2020.peer-reviewe