Rational Design, Synthesis, and Structure-Activity Relationship of a Novel Isoquinolinone-Based Series of HBV Capsid Assembly Modulators Leading to the Identification of Clinical Candidate AB-836.

Inhibition of Hepatitis B Virus (HBV) replication by small molecules that modulate capsid assembly and the encapsidation of pgRNA and viral polymerase by HBV core protein is a clinically validated approach toward the development of new antivirals. Through definition of a minimal pharmacophore, a series of isoquinolinone-based capsid assembly modulators (CAMs) was identified. Structural biology analysis revealed that lead molecules possess a unique binding mode, exploiting electrostatic interactions with accessible phenylalanine and tyrosine residues.

One-Year Mortality After Lung Transplantation: Experience of a Single French Center Between 2012 and 2021.

BACKGROUND Lung transplantation (LTx) is a life-extending therapy for specific patients with terminal lung diseases. This study aimed to evaluate the associations and causes of 1-year mortality after lung transplantation at Strasbourg University Hospital, France, between 2012 and 2021. MATERIAL AND METHODS We carried out a retrospective analysis on 425 patients who underwent LTx at Strasbourg University Hospital between January 1, 2012, and December 31, 2021.

Outcomes of lung transplantation for pleuroparenchymal fibroelastosis: A French multicentric retrospective study.

Background: Pleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented.

Methods: We conducted a nation-wide multicentric retrospective study in patients who underwent lung or heart-lung transplantation for chronic end-stage lung disease secondary to PPFE between 2012 and 2022 in France.

Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas.

Introduction: Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement.

Ethical considerations in xenotransplantation of thoracic organs - a call for a debate on value based decisions.

Xenotransplant covers a broad ethical territory and there are several ethical questions that have arisen in parallel with the technological advances that have allowed the first porcine transplants to occur. This brief communication highlights ethical considerations regarding heart and lung xenotransplantation, with an emphasis on unresolved value-based concerns in the field. The aim of this text is therefore to encourage the readers to consider the vast potential of this emerging technique to do good, but also the risk of doing harm, and to participate in a discussion.

Impact of adjuvant radiotherapy and chemotherapy on thymoma.

Purpose: Thymoma is a rare tumour. The most common treatment for thymoma is surgical resection, while the use of radiotherapy and chemotherapy remains controversial.

Patients And Methods: We conducted a monocentric observational study of 31 patients diagnosed with thymoma from June 2004 to July 2020 at cancer centre in Strasbourg, France.

vascularized immunocompetent patient-derived model to test cancer therapies.

This work describes a patient-derived tumoroid model (PDTs) to support precision medicine in lung oncology. The use of human adipose tissue-derived microvasculature and patient-derived peripheral blood mononuclear cells (PBMCs) permits to achieve a physiologically relevant tumor microenvironment. This study involved ten patients at various stages of tumor progression.

Controlled donation after circulatory death lung transplantation: Results of the French protocol including in situ abdominal normothermic regional perfusion and ex vivo lung perfusion.

Background: The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT).

Methods: We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021.

Results: One hundred grafts from 14 donor hospitals were accepted by 6 LT centers.

2022 Update of indications and contraindications for lung transplantation in France.

Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process.

[Updated indications and contraindications in 2022 for lung transplantation in France].

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis.

Outcome of lung oligometastatic patients treated with stereotactic body irradiation.

Purpose: The oligometastatic stage is an intermediate stage of cancer between the localized stage and polymetastatic stage. The prognosis of patients in this stage also appears to be intermediate. Lung stereotactic body radiotherapy is a possible tool for treating oligometastatic lung sites.

Patient-Derived Lung Tumoroids-An Emerging Technology in Drug Development and Precision Medicine.

Synthetic 3D multicellular systems derived from patient tumors, or tumoroids, have been developed to complete the cancer research arsenal and overcome the limits of current preclinical models. They aim to represent the molecular and structural heterogeneity of the tumor micro-environment, and its complex network of interactions, with greater accuracy. They are more predictive of clinical outcomes, of adverse events, and of resistance mechanisms.

Vascularization of Patient-Derived Tumoroid from Non-Small-Cell Lung Cancer and Its Microenvironment.

Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment.

Initiation of extracorporeal photopheresis in lung transplant patients with mild to moderate refractory BOS: A single-center real-life experience.

Background: Bronchiolitis obliterans syndrome (BOS) is the main limitation to long-term survival following lung transplantation. Several studies generated promising results regarding the efficacy of extracorporeal photopheresis (ECP) in BOS management. We aimed to compare FEV1 evolution in ECP-treated versus non-ECP treated patients among BOS recipients.