The expanded French compassionate programme for elexacaftor-tezacaftor-ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study.

Background: Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response.

Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease.

Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted.

Impaired performance of rapid grip in people with Parkinson's disease and motor segmentation.

Bradykinesia, or slow movement, is a defining symptom of Parkinson's disease (PD), but the underlying neuromechanical deficits that lead to this slowness remain unclear. People with PD often have impaired rates of motor output accompanied by disruptions in neuromuscular excitation, causing abnormal, segmented, force-time curves. Previous investigations using single-joint models indicate that agonist electromyogram (EMG) silent periods cause motor segmentation.

Successful lung transplantation in genetic methionyl-tRNA synthetase-related alveolar proteinosis/lung fibrosis without recurrence under methionine supplementation: Medium-term outcome in 4 cases.

Pulmonary alveolar proteinosis (PAP) results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages, and can be associated with pulmonary fibrosis, with a need for lung transplantation (LTx). Causes of PAP are autoimmune (90%-95%), secondary (5%), or hereditary (<1%). Patients with hereditary PAP are generally not considered for isolated LTx, due to the high probability of recurrence after LTx, and only a challenging scenario with sequential LTx followed by hematopoietic stem cell transplantation (HSCT) was reported as successful.

Mitochondrial membrane potential regulates nuclear DNA methylation and gene expression through phospholipid remodeling.

Maintenance of the mitochondrial inner membrane potential (ΔΨM) is critical for many aspects of mitochondrial function, including mitochondrial protein import and ion homeostasis. While ΔΨM loss and its consequences are well studied, little is known about the effects of increased ΔΨM. In this study, we used cells deleted of , a natural inhibitor of the hydrolytic activity of the ATP synthase, as a genetic model of mitochondrial hyperpolarization.

Theratyping cystic fibrosis patients to guide elexacaftor/tezacaftor/ivacaftor out-of-label prescription.

Background: Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator () gene. Considering that pwCF carrying rare variants may benefit from ETI, including variants already validated by the US Food and Drug Administration (FDA), a compassionate use programme was launched in France. PwCF were invited to undergo a nasal brushing to investigate whether the pharmacological rescue of CFTR activity by ETI in human nasal epithelial cell (HNEC) cultures was predictive of the clinical response.

Nonsense mutations accelerate lung disease and decrease survival of cystic fibrosis children.

Rationale: Limited information is available on the clinical status of people with Cystic Fibrosis (pwCF) carrying 2 nonsense mutations (PTC/PTC). The main objective of this study was to compare disease severity between pwCF PTC/PTC, compound heterozygous for F508del and PTC (F508del/PTC) and homozygous for F508del (F508del+/+).

Methods: Based on the European CF Society Patient Registry clinical data of pwCF living in high and middle income European and neighboring countries, PTC/PTC (n = 657) were compared with F508del+/+ (n = 21,317) and F508del/PTC(n = 4254).

Results of Lung Transplantation for Cystic Fibrosis With Selected Donors Over 65 Years Old.

Lung transplantation is limited by the shortage of suitable donors. Many programs have begun to use extended criteria donors. Donors over 65 years old are rarely reported, especially for young cystic fibrosis recipients.

The French Compassionate Program of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del variant.

Background: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) for people with cystic fibrosis (pwCF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for pwCF carrying one of 177 rare variants.

Methods: An observational study was conducted to evaluate the effectiveness of ETI in pwCF with advanced lung disease that were not eligible to ETI in Europe.

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.

Impact of the COVID-19 pandemic and associated lockdown measures on the management, health, and behavior of the cystic fibrosis population in France during 2020 (MUCONFIN).

Background: Most of the studies on cystic fibrosis (CF) focused on SARS-CoV-2 prevalence and suggested a low incidence of infection in this population. We aimed to assess the impact of the pandemic and related lockdown measures implemented in May 2020 in response to the first wave of SARS-CoV-2 infection on healthcare access, health, and behavior in CF patients.

Methods: A national questionnaire opened online from May 15th, 2020 to June 11, 2020 was completed by 751 CF-patients, aged 14 years and over.

[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.

Amikacin Liposomal Inhalation Suspension in the Treatment of Lung Infection: A French Observational Experience.

Background: infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of lung diseases. As an alternative, cohort studies may provide insightful information into the management of pulmonary disease.

Measures of motor segmentation from rapid isometric force pulses are reliable and differentiate Parkinson's disease from age-related slowing.

Some people with Parkinson's disease (PD) have disruptions in motor output during rapid isometric muscle contractions. Measures of such disruptions (motor segmentation) may help clarify disease subtype, progression, or effects of therapeutic interventions. We investigated the potential utility of segmentation measures by testing two hypotheses that are fundamental to measurement and evaluation.

Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial.

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), and restoring metabolic control in these patients may improve their management after lung transplantation. In this multicenter, prospective, phase 1-2 trial, we evaluate the feasibility and metabolic efficacy of combined pancreatic islet-lung transplantation from a single donor in patients with CFRD, terminal respiratory failure, and poorly controlled diabetes. Islets were infused via the portal vein under local anesthesia, 1 week after lung transplantation.

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis.

Background: Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.

Methods: Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease.

A virtual crossmatch-based strategy for perioperative desensitisation in lung transplant recipients with pre-formed donor-specific antibodies: 3-year outcome.

Background: Pre-formed donor-specific antibodies (DSAs) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. A virtual crossmatch-based strategy for perioperative desensitisation protocol has been used for immunised LTx candidates since 2012 at Foch Hospital (Suresnes, France). We compared the outcome of desensitised LTx candidates with high DSA mean fluorescence intensity and those with low or no pre-formed DSAs, not desensitised.

"Il faut continuer à poser des questions" patient reported outcome measures in cystic fibrosis: An anthropological perspective.

Background: People with cystic fibrosis (pwCF) are central in the development of patient-led assessment tools. Qualitative analysis of a frequently used CF-specific patient-reported outcome measure (PROM) sought patient recommendations for development of a new quality of life (QoL) tool.

Methods: We performed an inventory of PROMs, symptom-report and QoL tools used in clinical trials within the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) and in routine clinical practice among Cystic Fibrosis Europe and ECFS members.