Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma.

Objective: Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression.

Materials And Methods: We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution.

Efficacy of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma.

Background: Pulmonary sarcomatoid carcinomas (PSC) are notorious for their poor prognosis and resistance to chemotherapy. The literature suggests that immunotherapy might be effective against this aggressive tumor. This study aims to evaluate the efficacy of immunotherapy, either alone or combined with chemotherapy, as first-line treatment for PSC patients.

[Lung cancer screening: Update, news and perspectives].

Lung cancer is the leading cause of cancer death in France and worldwide (20 % of cancer deaths). This mortality is partly linked to an overrepresentation of metastatic stages at diagnosis (approximately 55 % of lung cancers at diagnosis). Low-dose chest CT in a target population to detect early forms accessible to radical treatment has been evaluated through multiple randomized trials (NLST, NELSON, MILD, DANTE…).

The impact of body composition parameters on severe toxicity of nivolumab.

Background: The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.

Is there an Exposure-Response Relationship for Nivolumab in Real-World NSCLC Patients?

Pharmacokinetic/pharmacodynamic data from real-world cohort are sparse in non small-cell lung cancer (NSCLC) patients treated with nivolumab. The aim of this prospective observational study was to explore the exposure-response relationship for effectiveness and toxicity of nivolumab in 81 outpatients with metastatic lung cancer. Nivolumab plasma trough concentrations (Cmin) were assayed at days 14, 28, and 42.

Hypermetabolism is an independent prognostic factor of survival in metastatic non-small cell lung cancer patients.

Background & Aims: Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients.

[IHC, FISH, CISH, NGS in non-small cell lung cancer: What changes in the biomarker era?].

Lung cancer is the leading cause of cancer deaths in France, with about 30,000 deaths per year. The overwhelming majority (90 %) are tobacco-related. The prognosis is dark but great therapeutic advances have been made with the development of targeted therapies first and then immunotherapy afterwards.

Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the EGFR inhibitors afatinib, erlotinib and osimertinib, the ALK inhibitor crizotinib and the VEGFR inhibitor nintedanib in human plasma from non-small cell lung cancer patients.

A new method for the quantitative analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of five tyrosine kinase inhibitors (afatinib, crizotinib, osimertinib, erlotinib and nintedanib) used in the treatment of non-small cell lung cancer (NSCLC) was developed and validated in human plasma. Separation was performed on an Accucore C18 (2.1 × 50 mm; 2.

5-HT receptor-dependent phosphorylation of mGlu receptor at Serine 843 promotes mGlu receptor-operated G signaling.

The serotonin 5-HT and glutamate mGlu receptors continue to attract particular attention, given their implication in psychosis associated with schizophrenia and the mechanism of action of atypical antipsychotics and a new class of antipsychotics, respectively. A large body of evidence indicates a functional crosstalk between both receptors in the brain, but the underlying mechanisms are not entirely elucidated. Here, we have explored the influence of 5-HT receptor upon the phosphorylation pattern of mGlu receptor in light of the importance of specific phosphorylation events in regulating G protein-coupled receptor signaling and physiological outcomes.

Resting energy expenditure in the risk assessment of anticancer treatments.

Background & Aims: Alterations of nutritional and performance status (PS) are associated with higher risk of chemotherapy toxicity. Increased resting energy expenditure (REE) is frequent in cancer patients and may contribute to cachexia. We investigated whether abnormal energetic metabolism could predict early acute limiting toxicities (ELT) of anticancer treatments.

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

Background And Aims: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre.

Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old.

Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC consecutive pts.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

Background/objectives: Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown.

Methods: Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded.

Spatial Orientation and Morphology of the Pulmonary Artery: Relevance to Optimising Design and Positioning of a Continuous Pressure Monitoring Device.

Personalised treatment of heart disease requires an understanding of the patient-specific characteristics, which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable of continuous monitoring of the left ventricle filling pressure, is a novel device for personalised management of patients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioning within the pulmonary artery and its relationship to the interrogating device on the chest wall on a patient-specific level.

Renin-associated hypertension after bronchial artery embolization in cystic fibrosis.

Bronchial artery embolization is the recommended therapy for massive hemoptysis in patients with cystic fibrosis (CF). We report on two cases of multiple renal infarcts and renin-associated hypertension and hypokalemia occurring in CF adults after bronchial artery embolizations. These complications were presumably related to crossing of small calibrated microspheres through arteriovenous anastomoses.

Reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin.

Background: Azithromycin reduces exacerbations in cystic fibrosis (CF) patients. Our aim was to investigate its association with nontuberculous mycobacteria isolation and macrolide susceptibility.

Methods: From 2006 to 2010, all adult CF subjects at Cochin Hospital (Paris, France) harboring at least one positive NTM isolate were identified (Cases).

Complications of peripherally inserted central catheters in adults with cystic fibrosis or bronchiectasis.

Background: Peripherally inserted central catheters (PICCs) are increasingly used in patients with cystic fibrosis (CF) or with non-CF bronchiectasis, but little data exist on catheter-related complications in this setting.

Methods: Prospective follow-up of consecutive PICCs inserted for intravenous (IV) antibiotics in adults with CF or with non-CF bronchiectasis at Cochin Hospital (Paris, France).

Results: Between March 2009 and December 2011, 182 PICCs were prescribed in 117 adults (67 CF and 50 non-CF patients).

3D-modelling of transient left bronchial obstruction following bidirectional superior cavopulmonary shunt.

Extrinsic compression of airways is one the most important causes of respiratory insufficiency in the perioperative period in children with congenital heart disease. This is especially true of pathologies that involve surgery of the aortic arch or conduit replacement of the right ventricular outflow tract. However bronchial obstruction is uncommon in the setting of bidirectional cavopulmonary shunt alone.

Inaugural bone metastases in non-small cell lung cancer: a specific prognostic entity?

Background: In non-small cell lung cancer patients (NSCLC), median survival from the time patients develop bone metastasis is classically described being inferior to 6 months. We investigated the subcategory of patients having an inaugural skeletal-related-event revealing NSCLC. The purpose of this study was to assess the impact of bone involvement on overall survival and to determine biological and tumoral prognosis factors on OS and PFS.

Prognostic value of six minute walk test in cystic fibrosis adults.

Background: The 6 min walk test (6MWT) provides prognostic information in various respiratory diseases, but limited data exist in cystic fibrosis (CF) adults.

Methods: Consecutive CF adults who performed 6MWT at Cochin Hospital (Paris, France) over 12 years were analyzed. The cut-off 6 min walking distance (6MWD) value that best predicted a combined endpoint (death without transplant or lung transplant) was established using a receiver operating curve.

Rapid emergence of resistance to linezolid and mutator phenotypes in Staphylococcus aureus isolates from an adult cystic fibrosis patient.

Linezolid has emerged as an important therapeutic option for the treatment of Staphylococcus aureus in patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistant S. aureus clinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.

Lessons from patient-specific 3D models of the cardiac chambers after the Mustard operation.

The recent ability to create detailed 3D models of the atrial and ventricular chambers using CT, MRI and rapid prototyping offers unique opportunities to study the size and shape of the different cardiac chambers both before and following operation for complex cardiac anomalies. We here describe the techniques for creating detailed 3D models of the heart and demonstrate the utility of these techniques in a patient studied after the Mustard operation. This can give important insights into the changes in size and shape of the different chambers and the patterns of blood flow from the pulmonary and systemic veins to the 'appropriate' ventricle.