Use of circulating tumor cells in prospective clinical trials for NSCLC patients - standardization of the pre-analytical conditions.

BACKGROUND: Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage. METHODS: Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs. RESULTS: Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement. CONCLUSIONS: The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

Assessment of oxidative stress after out-of-hospital cardiac arrest.

INTRODUCTION: Pathophysiology of cardiac arrest corresponds to a whole body ischemia-reperfusion. This phenomenon is usually associated with an oxidative stress in various settings, but few data are available on cardiac arrest in human. The aim of the present study was to evaluate different oxidative stress markers in out-of-hospital cardiac arrest (OHCA) patients treated with therapeutic hypothermia. MATERIALS AND METHODS: We conducted a prospective study assessing oxidative stress markers (thiobarbituric acid reactive species, carbonyls, thiols, glutathione, and glutathione peroxidase) in OHCA patients treated with therapeutic hypothermia. Measurements were performed during the 4 days after admission and compared between good and poor outcome patients according to Cerebral Performance Category. RESULTS: Thirty-four patients were included, 10 good and 24 poor outcomes at 6 months. Thiobarbituric acid reactive species were higher in the poor outcome group on admission and when therapeutic hypothermia was reached. The other markers were not different between groups. No markers seemed modified by the use of therapeutic hypothermia in each group. CONCLUSIONS: After OHCA, good outcome patients exhibit lower oxidative stress markers than poor outcome patients. Thiobarbituric acid reactive species appears to be an early prognostic parameter. Oxidative stress markers seem not mitigated by therapeutic hypothermia.

Critical Assessment in Routine Clinical Practice of Liquid Biopsy for EGFR Status Testing in Non-Small-Cell Lung Cancer: A Single-Laboratory Experience (LPCE, Nice, France).

BACKGROUND: The introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). PATIENTS AND METHODS: A total of 345 samples were analyzed using the US Food and Drug Administration-approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients. RESULTS: Cobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable. CONCLUSION: PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.

Comparison of presumed cardiac and respiratory causes of out-of-hospital cardiac arrest.

AIMS OF THE STUDY: Most interventional and observational studies include cardiac arrest from cardiac origin. However, an increasing proportion of cardiac arrest results from an extra-cardiac origin, mainly respiratory. The aim of our study was to compare the characteristics and outcome of cardiac arrest patients according to the presumed cardiac or respiratory causes. METHODS: This retrospective multicenter observational study included out-of-hospital cardiac arrest patients from presumed cardiac and respiratory origin treated with therapeutic hypothermia. Demographic data (age, sex, initial rhythm as shockable or non-shockable, durations of no-flow and low-flow), clinical evolution in ICU, lactate and outcome (CPC scale at ICU discharge) were compared between patients according to the presumed cardiac or respiratory origin of the cardiac arrest. RESULTS: Two hundred and fifty-one cardiac arrest patients were included, 156 from presumed cardiac origin (62%) and 95 from presumed respiratory origin (38%). Patients with presumed cardiac cause presented more frequently a shockable rhythm (68% vs. 5%, p < 0.001), received more defibrillations attempts (2 [1-5] vs. 0 [0-0], <0.001) and needed less adrenaline (3 mg [0-5] vs. 4 mg [2-7], p = 0.01). The arterial lactate concentration on admission was higher in patients with presumed respiratory causes (6.3 mmol/L [4.2-9.8] vs. 3.2 mmol/L [1.6-5.0], p < 0.001). The proportion of patients presenting a favorable outcome was higher in the population with presumed cardiac causes, compared to its respiratory counterpart (42% vs. 19%, p < 0.001). CONCLUSIONS: Compared to presumed cardiac origin, a worse outcome and a different mode of death are associated with the presumed respiratory origin, resulting from a greater insult preceding cardiac arrest. The presumed cause of cardiac arrest could be integrated in the multimodal prognostication process.

Association of serum lactate with outcome after out-of-hospital cardiac arrest treated with therapeutic hypothermia.

AIMS: Lactate reflects hypoxic insult in many conditions and is considered as a prognosis factor. But, after cardiac arrest, its interest is still debated. Our study aimed to assess the prognosis value of lactate in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. METHODS: This retrospective observational study included out-of-hospital cardiac arrest patients treated with therapeutic hypothermia in four ICUs. Lactate levels were compared at different times during the first 24 hours according to outcome at ICU discharge and to the type of death (multiorgan or neurologic failure). RESULTS: Two hundred and seventy-two patients were included, 89 good outcome and 183 poor outcome. In the latter group, 171 patients died, from multiorgan failure in 30% and neurologic failure in 70%. Lactate levels were higher in the poor compared to the good outcome patients at admission (5.4 (3.3-9.4) vs. 2.2 (1.5-3.6) mmol/L; p<0.01), 12 hours (2.5 (1.6-4.7) vs. 1.4 (1.0-2.2) mmol/L; p<0.01) and 24 hours (1.8 (1.1-2.8) vs. 1.3 (0.9-2.1) mmol/L; p<0.01). Patients succumbing from multiorgan failure exhibited higher lactate levels compared to those dying from neurologic failure at admission (7.9 (3.9-12.0) vs. 5.2 (3.3-8.8) mmol/L; p<0.01), H12 (4.9 (2.1-8.9) vs. 2.2 (1.4-3.4) mmol/L; p<0.01) and H24 (3.3 (1.8-5.5) vs. 1.4 (1.1-2.5) mmol/L; p<0.01). Initial lactate levels showed an increasing proportion of poor outcome from the first to fourth quartile. CONCLUSIONS: After out-of-hospital cardiac arrest treated with therapeutic hypothermia, lactate levels during the first 24 hours seem linked with ICU outcome. Patients dying from multiorgan failure exhibit higher initial lactate concentrations than patients succumbing from neurological failure.

Compressive hematoma and deep arteriovenous malformation: Emergency endovascular occlusion via a venous approach with surgical evacuation of the hematoma.

Compressive hematoma associated with deep arterio-venous malformation is a difficult surgery. Arterial presurgical embolization is often indicated but rarely effective. Endovascular occlusion via a venous approach is a technique that has recently been undertaken successfully to treat certain types of sub-pial vascular malformation. The venous endovascular approach has succeeded in a 20-year-old man of who presented with a compressive hematoma due to rupture of a deep arteriovenous malformation. By fully endovascular occlusion, the surgery consisted of surgical removal of the hematoma, with reduced cortical damage.

The practice of therapeutic hypothermia after cardiac arrest in France: a national survey.

AIMS: Cardiac arrest is a major health concern worldwide accounting for 375,000 cases per year in Europe with a survival rate of <10%. Therapeutic hypothermia has been shown to improve patients' neurological outcome and is recommended by scientific societies. Despite these guidelines, different surveys report a heterogeneous application of this treatment. The aim of the present study was to evaluate the clinical practice of therapeutic hypothermia in cardiac arrest patients. METHODS: This self-declarative web based survey was proposed to all registered French adult intensive care units (ICUs) (n=357). Paediatrics and neurosurgery ICUs were excluded. The different questions addressed the structure, the practical modalities of therapeutic hypothermia and the use of prognostic factors in patients admitted after cardiac arrest. RESULTS: One hundred and thirty-two out of 357 ICUs (37%) answered the questionnaire. Adherence to recommendations regarding the targeted temperature and hypothermia duration were 98% and 94% respectively. Both guidelines were followed in 92% ICUs. During therapeutic hypothermia, sedative drugs were given in 99% ICUs, mostly midazolam (77%) and sufentanil (59%). Neuromuscular blocking agents (NMBA) were used in 97% ICUs, mainly cisatracurium (77%). Numerous prognostic factors were used after cardiac arrest such as clinical factors (95%), biomarkers (53%), electroencephalography (78%) and evoked potentials (35%). CONCLUSIONS: In France, adherence to recommendations for therapeutic hypothermia after cardiac arrest is higher than those previously reported in other countries. Numerous prognostic factors are widely used even if their reliability remains controversial.