Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

CyberKnife for hilar lung tumors: report of clinical response and toxicity

<p>Abstract</p> <p>Objective</p> <p>To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors.</p> <p>Methods</p> <p>Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals.</p> <p>Results</p> <p>Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy.</p> <p>Conclusion</p> <p>CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.</p

Endovascular coils as lung tumour markers in real-time tumour tracking stereotactic radiotherapy: preliminary results

To evaluate the use of endovascular coils as markers for respiratory motion correction during high-dose stereotactic radiotherapy with the CyberKnife, an image-guided linear accelerator mounted on a robotic arm. Endovascular platinum embolisation coils were used to mark intrapulmonary lesions. The coils were placed in subsegmental pulmonary artery branches in close proximity to the target tumour. This procedure was attempted in 25 patients who were considered unsuitable candidates for standard transthoracic percutaneous insertion. Vascular coils (n = 87) were succesfully inserted in 23 of 25 patients. Only minor complications were observed: haemoptysis during the procedure (one patient), development of pleural pain and fever on the day of procedure (one patient), and development of small infiltrative changes distal to the vascular coil (five patients). Fifty-seven coils (66% of total inserted number) could be used as tumour markers for delivery of biologically highly effective radiation doses with automated tracking during CyberKnife radiotherapy. Endovascular markers are safe and allow high-dose radiotherapy of lung tumours with CyberKnife, also in patients who are unsuitable candidates for standard transthoracic percutaneous marker insertion

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Neutrophil morphology and migration are affected by substrate elasticity

To reach sites of inflammation, neutrophils execute a series of adhesion and migration events that include transmigration through the vascular endothelium and chemotaxis through the vicinal extracellular matrix until contact is made with the point of injury or infection. These in vivo microenvironments differ in their mechanical properties. Using polyacrylamide gels of physiologically relevant elasticity in the range of 5 to 100 kPa and coated with fibronectin, we tested how neutrophil adhesion, spreading, and migration were affected by substrate stiffness. Neutrophils on the softest gels showed only small changes in spread area, whereas on the stiffest gels they showed a 3-fold increase. During adhesion and migration, the magnitudes of the distortions induced in the gel substrate were independent of substrate stiffness, corresponding to the generation of significantly larger traction stresses on the stiffer gels. Cells migrated more slowly but more persistently on stiffer substrates, which resulted in neutrophils moving greater distances over time despite their slower speeds. The largest tractions were localized to the posterior of migrating neutrophils and were independent of substrate stiffness. Finally, the phosphatidylinositol 3-kinase inhibitor LY294002 obviated the ability to sense substrate stiffness, suggesting that phosphatidylinositol 3-kinase plays a mechanistic role in neutrophil mechanosensing

Supplementary Material for: Cl-Amidine Prevents Histone 3 Citrullination and Neutrophil Extracellular Trap Formation, and Improves Survival in a Murine Sepsis Model

<p>Sepsis refers to the presence of a serious infection that correlates with systemic and uncontrolled immune activation. Posttranslational histone modification plays an important role in chromatin decondensation, which is regulated by citrullination. Citrullinated histone H3 (H3cit) has been identified as a component of neutrophil extracellular traps (NETs), which are released into the extracellular space as part of the neutrophil response to infection. The conversion of arginine to citrulline residues on histones is catalyzed by peptidylarginine deiminase 4 (PAD4). This study's goals were to characterize the presence of PAD4-catalyzed H3cit and NET formation during the onset of sepsis and elucidate the effects on the immune response when this mechanism of action is blocked. Adult C57BL/6 male mice were treated with Cl-amidine, an inhibitor of PAD4, 1 h prior to sepsis induced by cecal ligation and puncture (CLP). Twenty-four hours after CLP, cytokine levels, H3cit protein expression, neutrophil counts, and NET production were evaluated in the peritoneal cavity. Survival studies were also performed. Here we demonstrate that Cl-amidine treatment prior to CLP improves overall survival in sepsis and the abrogation of PAD4 has minimal effects on the proinflammatory immune response to sepsis, while it has no effect on overall neutrophil migration to the peritoneum.</p

CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell line U937 via LFA-1/ICAM-1 pathway

CD147 is a 50 000–60 000 MW glycoprotein of the immunoglobulin superfamily broadly expressed on haemopoietic cell lines and peripheral blood cells. In the present study, six monoclonal antibodies (mAbs) directed against the CD147 protein were generated. The antigen defined by the generated CD147 mAbs is widely expressed on haemopoietic cell lines, peripheral blood cells and is a lymphocyte activation-associated cell surface molecule. The generated CD147 mAbs precipitated a broad protein band from U937 cells of 45 000–65 000 MW under reducing conditions. Functional analysis indicated that the CD147 mAbs markedly induced homotypic cell aggregation of U937 cells, but not K562 cells. The CD147 mAb-induced cell aggregation was inhibited by leucocyte function-antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) mAbs. However, the expression of LFA-1 and ICAM-1 molecules on U937 was not altered by CD147 mAb treatment. The U937 cell aggregation induced by CD147 mAb was also inhibited by ethylenediamine tetra-acetic acid (EDTA), sodium azide and when incubated at 4°. We therefore propose that the binding of CD147 mAb to CD147 molecule, which mimics the natural ligand binding, may generate intracellular signals that activate LFA-1/ICAM-1 intercellular adhesion pathway