Multiplexed Profiling of CDK Kinase Activities in Tumor Biopsies with Fluorescent Peptide Biosensors.

Detection of disease biomarkers constitutes a major challenge for the development of personalized and predictive diagnostics as well as companion assays. Protein kinases (PKs) involved in the coordination of cell cycle progression and proliferation that are hyperactivated in human cancers constitute attractive pharmacological targets and relevant biomarkers. Although it is relatively straightforward to assess the relative abundance of PKs in a biological sample, there is not always a direct correlation with enzymatic activity, which is regulated by several posttranslational mechanisms.

Brief Report: A Multidisciplinary Initial Workup for Suspected Lung Cancer as Fast-Track Intervention to Histopathologic Diagnosis.

Guidelines for optimal timing of lung cancer diagnosis and treatment have been implemented in many countries, but the effect of fast-track interventions on the shortening of time interval is still debatable. In this study, the delay from the first specialist visit to the histopathologic diagnosis was compared between two patient cohorts: before (n = 280) and after (n = 247) implementation of a fast-track multidisciplinary diagnosis program. The cumulative incidence function curves were compared, and hazard ratio was adjusted in the Cox model.

Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series.

Background: Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.

EGFR-dependent mechanisms of resistance to osimertinib determined by ctDNA NGS analysis identify patients with better outcome.

Background: Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is highly selective for subclones in patients with non-small cell lung cancer (NSCLC). Unfortunately, all patients develop resistance through EGFR-dependent or EGFR-independent pathways. Recently, circulating tumoral DNA (ctDNA) analysis has highlighted the usefulness of plasma genotyping for exploring patient survival outcomes after disease progression under osimertinib.

Complication and lung function impairment prediction using perfusion and computed tomography air trapping (CLIPPCAIR): protocol for the development and validation of a novel multivariable model for the prediction of post-resection lung function.

Background: Recent advancements in computed tomography (CT) scanning and post processing have provided new means of assessing factors affecting respiratory function. For lung cancer patients requiring resection, and especially those with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), the ability to predict post-operative lung function is a crucial step in the lung cancer operability assessment. The primary objective of the CLIPPCAIR study is to use novel CT data to develop and validate an algorithm for the prediction of lung function remaining after pneumectomy/lobectomy.

Club Cell Loss as a Feature of Bronchiolization in ILD.

Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1 bronchiolar-specific club cell may play a role in this aberrant regenerative process. To assess the presence of club cells in the small airways of patients suffering from ILD.

Combination of tissue and liquid biopsy molecular profiling to detect transformation to small cell lung carcinoma during osimertinib treatment.

Background: Histological transformation of advanced non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the mechanisms of resistance to third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib. This acquired TKI resistance is linked to the high degree of tumor heterogeneity and adaptive cellular signaling pathways, including epidermal growth factor receptor ()-dependent pathways, observed in NSCLC.

Methods: Here, we investigated a series of paired pre- and post-histological transformation biopsies obtained from three patients initially having a NSCLC with an mutation treated with first-generation TKI, who then received osimertinib as second-line after resistance and, lastly, developed a histological transformation to SCLC.

Homoplasmic deleterious MT-ATP6/8 mutations in adult patients.

To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis.

Childhood pulmonary Langerhans cell histiocytosis: a comprehensive clinical-histopathological and BRAF mutation study from the French national cohort.

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAF mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.

Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.

The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA.

Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?

Background And Purpose: We aimed to identify the best definition of early neurological improvement (ENI) at 2 and 24 hours after mechanical thrombectomy (MT) and determine its ability to predict a good functional outcome at 3 months.

Methods: This retrospective analysis was based on a prospectively collected registry of patients treated by MT for ischemic stroke from May 2010 to March 2017. We included patients treated with stent-retrievers with National Institute of Health Stroke Scale (NIHSS) score before treatment and at 2 and/or 24 hours after treatment and modified Rankin Score (mRS) at 3 months.

Mechanical Thrombectomy for Tandem Occlusions of the Internal Carotid Artery-Results of a Conservative Approach for the Extracranial Lesion.

Mechanical thrombectomy (MT) is of clinical benefit for patients with extracranial-intracranial tandem lesions of anterior circulation. However, the optimal approach to the cervical lesion of the internal carotid artery (ICA) during MT has yet to be established. Data on a conservative approach for the proximal lesion during the acute phase are scarce.

SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with an aggressive clinical course and specific genetic alterations of the BAF chromatin remodeling complex. In the present study, we reviewed the clinical and pathologic features of 30 cases of SMARCA4-DTS, discussed its main differential diagnoses and the challenging diagnostic scenarios that the average pathologist may face. In addition, we tested the specificity of the "SMARCA4-DTS immunohistochemical signature" (co-loss of SMARCA4 and SMARCA2 with overexpression of SOX2) in a large cohort of intrathoracic malignancies.

Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) represent a novel molecular target in a small subset of tumors. Although ALK rearrangements are usually assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), molecular approaches have recently emerged as relevant alternatives in routine laboratories. Here, we evaluated the use of two different amplicon-based next-generation sequencing (NGS) methods (AmpliSeq and ArcherFusionPlex) to detect ALK rearrangements, and compared these with IHC and FISH.

Delayed pulmonary arterial hypertension in relation to pulmonary damage score after pneumonectomy under protective ventilation: experimental study.

Objective: To characterize pulmonary hemodynamic changes in relation to lung injury at 2 time points [48 h (H48) and 168 h (H168)] after pneumonectomy under intraoperative protective ventilation in order to improve postpneumonectomy pulmonary edema (PPE) prevention.

Method: Fifteen pigs (25 ± 1.9 kg) were randomly allocated to nonsurgical (control, n = 5) and surgical (H48 and H168) groups.

Impact of preoperative marking coils on surgical and pathologic management of impalpable lung nodules.

Background: The management of occult lung lesions, particularly subsolid opacities, is a new challenge because they are difficult to localize during surgery and the number of lesions detected by computed tomography (CT) is increasing.

Methods: Between February 2008 and December 2011, preoperative CT-guided marking with coils was systematically carried out to localize presumed impalpable nodules before video-assisted thoracoscopic surgery (VATS). The procedure feasibility, reliability, and safety as well as its impact on the resection volume and on the pathologic examination strategy were examined.

Outcome after mechanical thrombectomy using a stent retriever under conscious sedation: comparison between tandem and single occlusion of the anterior circulation.

Background And Purpose: In acute ischemic stroke patients, internal carotid artery/middle cerebral artery (ICA/MCA) occlusion in tandem predicts a poor outcome after systemic thrombolysis. This study aimed to compare outcomes after mechanical thrombectomy for tandem and single occlusions of the anterior circulation.

Materials And Methods: This prospective study included consecutive patients with acute ischemic stroke of the anterior circulation who had undergone mechanical thrombectomy performed with a stent retriever under conscious sedation within 6h of symptom onset.

Predictive factors of outcome and hemorrhage after acute ischemic stroke treated by mechanical thrombectomy with a stent-retriever.

Introduction: The study attempts to identify notable factors predicting poor outcome, death, and intracranial hemorrhage in patients with acute ischemic stroke undergoing mechanical thrombectomy with stent retriever. These data could be useful to improve the selection of patients for thrombectomy.

Methods: Patients with acute ischemic stroke treated with the Solitaire FR device were retrospectively analyzed from a prospectively collected database.

Can diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch (positive diffusion-weighted imaging/negative fluid-attenuated inversion recovery) at 3 Tesla identify patients with stroke at <4.5 hours?

Background And Purpose: At 1.5 T, diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch helps identify strokes within 4.5 hours of onset.

Can renal biopsy accurately predict histological subtype and Fuhrman grade of renal cell carcinoma?

Purpose: We determined the accuracy of renal biopsy in predicting histological subtype and final Fuhrman nuclear grade in small (4 cm or smaller) renal cancers, and evaluated the concordance between renal biopsy and surgery for these 2 criteria.

Materials And Methods: A total of 187 percutaneous needle biopsies of small renal tumors, guided by computerized tomography with gauge needles and a coaxial technique, were consecutively performed between 2006 and 2011. Renal cell carcinoma was diagnosed in 132 tumors.

Characterization of small solid renal lesions: can benign and malignant tumors be differentiated with CT?

Objective: The purpose of this study was to evaluate the diagnostic performance of CT in determining whether a small solid renal enhancing mass is benign or malignant.

Materials And Methods: Ninety-nine biopsies of enhancing solid renal masses 4 cm or smaller without fat on CT scans were performed under CT fluoroscopic guidance. The growth pattern, interface with parenchyma, presence of a scar and segmental inversion enhancement, unenhanced CT histogram, and pattern and degree of enhancement on triphasic MDCT images were independently evaluated by two radiologists.

Fatal systemic nocardia infection revealed by cardiac tamponade.

We report the case of a 50-year-old man admitted for cardiac tamponade. He was diagnosed with acute pneumonia. He had no previous medical history, but exhibited a body mass index of 41.