In eight healthy volunteers we simultaneously measured the axial diaphragmatic motion by fluoroscopy and the cross-sectional area changes of the rib cage (RC) and abdomen (ABD) by Respitrace (RIP) during semistatic vital capacities (VC). We found that, if the fluoroscopic axial displacement of the posterior part of the diaphragm between residual volume (RV) and total lung capacity (TLC) is considered equal to 100%, the movement of the middle part is 90%, whereas that of the anterior part is only approximately 60%; the ratio of the axial displacements to mouth volume, furthermore, decreases at high lung volumes, especially for the anterior part. The RIP signal is nearly linearly related to mouth volume, but the contribution of the RC (delta RC) progressively increases (and is approximately 80% RIP at TLC), whereas the volume contribution of the ABD (delta ABD) levels off (to 20% RIP at TLC). The diaphragmatic volume displacement calculated from the theoretical analysis described by Mead and Loring also levels off at high volumes similarly as the ABD but is approximately 50% RIP at TLC. Finally, the axial movements of the three parts of the diaphragm are linearly related to the RC and ABD cross-sectional-area changes (r 0.91-0.97) and are even significantly better correlated with the "calculated" diaphragmatic volume displacement.
Lung cancer is the number one cause of cancer‐related death worldwide with cigarette smoking as its major risk factor. Although the incidence of lung cancer in never smokers is rising, this subgroup of patients is underrepresented in genomic studies of lung cancer. Here, we assembled a prospective cohort of 46 never‐smoking, nonsmall cell lung cancer (NSCLC) patients and performed whole‐exome and low‐coverage whole‐genome sequencing on tumors and matched germline DNA. We observed fewer somatic mutations, genomic breakpoints and a smaller fraction of the genome with chromosomal instability in lung tumors from never smokers compared to smokers. The lower number of mutations, enabled us to identify TSC22D1 as a potential driver gene in NSCLC. On the other hand, the frequency of mutations in actionable genes such as EGFR and ERBB2 and of amplifications in MET were higher, while the mutation rate of TP53, which is a negative prognostic factor, was lower in never smokers compared to smokers. Together, these observations suggest a more favorable prognosis for never smokers with NSCLC. Classification of somatic mutations into six‐substitution type patterns or into 96‐substitution type signatures revealed distinct clusters between smokers and never smokers. Particularly, we identified in never smokers signatures related to aging, homologous recombination damage and APOBEC/AID activity as the most important underlying processes of NSCLC. This further indicates that second‐hand smoking is not driving NSCLC pathogenesis in never smokers.
We studied the mechanical effectiveness of the parasternal intercostals at FRC and near TLC in 14 supine, vagotomized, and anesthetized dogs. First, we determined the relationship between parasternal intramuscular pressure (Pps), measured with Gaeltec 12 CT-mini-transducers, and parasternal EMG activity (Eps) during breathing at FRC and near TLC. Second, we examined the changes in Pps and the changes in parasternal force (Fps) generated during bilateral parasternal stimulation at FRC and near TLC with a given supramaximal stimulus. Before phrenicotomy, the inspiratory increases in Pps remained relatively constant near TLC (FRC, 50.4 +/- 16.5 versus TLC, 48.7 +/- 13.3 cm H2O, NS), whereas the Eps clearly decreased (82.9 +/- 5.5% FRC, p less than 0.01). This indicates that the gain converting electrical activity into pressure for the parasternals is greater near TLC than at FRC. A similar pattern of changes in Pps and in Eps was observed during quiet inspiration at FRC and near TLC after phrenicotomy. During bilateral parasternal stimulation the increases in Pps near TLC tended to be greater than those at FRC (140.7 +/- 28.6 versus 100 +/- 28.3 cm H2O, NS), whereas the increases in Fps were significantly greater near TLC than at FRC (277.4 +/- 60.6 versus 214.2 +/- 47.1 g, p less than 0.05). Therefore, we conclude that the mechanical effectiveness of the parasternal contraction near TLC remains relatively unchanged and is even greater in relation to that at FRC.
Background Treatment of patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) continues to evolve expeditiously. Objectives This retrospective study investigated real-world treatment patterns and EGFR mutation testing in patients with EGFRm advanced NSCLC in Belgium. Methods Data were extracted from medical records of adults diagnosed with EGFRm locally advanced/metastatic NSCLC between 1 September 2015 and 31 December 2017. Patients were followed retrospectively from diagnosis until 1 September 2018, end of clinical activity or death. Data on demographics, patient outcomes and disease characteristics, treatment patterns and EGFR mutation testing at diagnosis and progression were analyzed descriptively. Results A total of 141 patients were enrolled. At diagnosis, median age was 69 years, 63.1% were female, 88.7% had metastatic disease, 94.3% had adenocarcinoma histology, 76.6% had ECOG 0/1, 70.9% had common EGFR mutations and 29.1% had only rare mutations. In first line, 73.8% of patients received first/second-generation EGFR-tyrosine kinase inhibitors (1G/2G EGFR-TKIs), while 21.9% received other systemic treatments. Among 61 patients progressing on and discontinuing a first 1G/2G EGFR-TKI, 45 (73.8%) received subsequent systemic treatment while 16 (26.2%) did not; 20 (32.8%) received osimertinib. Among 65 patients progressing on a first 1G/2G EGFR-TKI, 47 (72.3%) were tested for T790M, of whom 25 (53.2%) were positive. Conclusion These real-world data from Belgium show that a substantial fraction of patients with EGFRm NSCLC do not receive 1G/2G EGFR-TKIs in first line and do not receive subsequent systemic treatment after progression on 1G/2G EGFR-TKIs. Only a third receive osimertinib upon progression on 1G/2G EGFR-TKIs. These observations should be considered in first-line treatment decisions. Trial Registration ClinicalTrials.gov: NCT03761901
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