Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort.

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

Intestinal endoparasitism in wild cat (Felis silvestris) from Banat area (Romania).

The wild cat (Felis silvestris), spread in Romania from the Danube Delta to the mountain range is present in the Banat area, on the hunting ground that can be contaminated with different stage developmental forms of parasites, some of them having real zoonotic potential. The wild cat is an animal protected by the Romanian law of protection animals. Coprological samples from 88 wild cats from 16 hunting grounds, as well as the gastrointestinal tract collected from six wild cats cadavers and the molecular characterization of the cestodes identified in their intestines, allowed us to establish intestinal parasitic fauna. During coprological examination Isospora oocysts, tapeworm eggs, eggs of Toxocara cati, Ancylostoma spp. and Capillaria spp were found. At the same time, the form of genera Mesocestoides, Taenia, Toxocara/Toxascaris and Ancylostoma were identified at necropsy. Further polymerase chain reaction (PCR) identification revealed the species of Taenia taenieformis, and Mesocestoides litteratus, the latter providing a zoonotic potential. This study, the first in the western part of the country (Banat area, Timis County), provides information about the parasitic fauna of wild cats and underlines the importance of the human contamination risk.

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Impact of ferric carboxymaltose on the evolution of hemoglobin and ECOG performance status in iron-deficient patients with solid tumors: a 3-month follow-up retrospective study.

BACKGROUND: Anemia is often associated with a lower quality of life and less tolerance to treatments in cancer patients. OBJECTIVE: The aims of this retrospective study were to assess the biological (hemoglobin, Hb) and clinical (ECOG index) impact of ferric carboxymaltose (FCM) and to identify predictive factors of response in cancer patients with iron deficiency. METHODS: We included 133 patients with solid tumors who received at least one dose of FCM in 2015. RESULTS: At baseline, most patients had metastatic cancer (70%), were undergoing chemotherapy (82%), suffered from anemia (90%), and 72% had an ECOG 0-1 index. Mean Hb level was statistically higher at M1 (108.3 g/L ± 13.9), M2 (110.3 g/L ± 16.1), and M3 (111.7 g/L ± 12.6) than M0 (99.2 g/L ± 13.9). Mean ECOG score increased significantly at M1 (1.31 ± 0.80) and M2 (1.31 ± 0.87) compared to M0 (1.13 ± 0.80). Variations of ECOG index between M0 and M1 were independent of levels of Hb and ferritin at inclusion and pretreatment use of transfusion and ESAs. Increase of Hb level was higher in patients with Hb < 100 g/L, ferritinemia < 800 ng/ml, or transfused before inclusion. In multivariate analysis, an ECOG index of 0 was the only predictive factor of an increase of ECOG index and Hb level < 100 g/L and ferritinemia < 800 ng/ml were predictive of an increase in Hb. CONCLUSION: Even though there was no improvement in ECOG index, this study did identify an increase of Hb for patients receiving FCM, indicating its potential benefit in iron-deficient cancer patients.

Self-organization and FORC-based magnetic characterization of ultra-high aspect ratio epitaxial Co nanostrips produced by oblique deposition on an ordered step-bunched silicon surface.

Further development of microelectronics requires novel or improved technological approaches for device nanofabrication and functional properties characterization. In this paper, we studied the crystal structure and magnetic properties of epitaxial Co nanostrips with the average width of 32.6, 45.3, and 62.6 nm grown on a step-bunched Si(111)5.55 × 5.55-Cu/Cu surface. Technological conditions, under which the ultra-high aspect ratio (∼104) structurally solid, straight nanostrips of hcp-Co with crystallographic axis [0001] oriented along their long side can be grown, were determined. The dependence of the coercive force on the width of the nanostrips was demonstrated. Magnetization reversal through the transverse domain-wall nucleation and propagation in a Co nanostrip was defined with an analytical approach based on the Stoner-Wohlfarth model. Using the first-order reversal curve method, we analyzed the effect of nanostrip uniformity degree on magnetic behavior and the influence of the magnetostatic interactions on the coercive force of individual nanostrips.

Deterministic and non-deterministic switching in chains of magnetic hysterons.

This paper presents a fundamental analysis of a single-domain ferromagnetic particles chain hysteresis in perpendicular geometry as a prototype for ultra-high density memories. Due to magnetostatic long range interactions the system has a complex hysteresis but stable features can be found. The loop has a number of deterministic Barkhausen jumps and consequently a number of stable plateaus that could be used in multistate memories. The fundamental elements that sustain this behavior are shown and discussed.

Web-based tool for injury risk assessment of foreign body injuries in children.

Web-based surveillance systems enhance the ability for identifying, estimating and assessing public health hazards. In this paper we describe the development of a Web-based surveillance registry called Susy Safe for inorganic foreign body injuries in children aged 0-14. The Susy Safe system, which collected 2103 cases during 2000-2002 in 19 European countries, allows for notifying from physicians over the internet thus taking advantage of Web reporting capabilities. Functions include automated risk analysis engine and results visualization. Risk analysis engine has been implemented in a Bayesian framework and provides an update estimate of the risk profile of the products causing injuries, effectively as new data become available. The system contributes to simplify the physician reporting and improve public health information dissemination within consumers and consumers' association. Also it gives physician and researcher the access of a large amount of data otherwise scattered all around in different hospitals. Finally, supplying a quantitative risk assessment for the identification of hazardous characteristics of objects, such as dimensions or shape, it works toward an improvement of consumer products' safety design.

The cost of foreign body injuries in the upper aero-digestive tract: need for a change from a clinical to a public health perspective?

OBJECTIVE: This paper addressed the impact in terms of direct costs of the injuries in children due to foreign bodies in the upper aero-digestive tract. METHODS: Two thousand one hundred and three consecutive cases were collected from 2000 to 2002 in 16 European hospitals, 1 hospital for each participating country, and referred to children aged until 14 who had FB injuries. Costs were based on the extraction of the FB procedures and on hospitalization length, based on DRGs. Determinants of costs and of length of stay (LOS) were analyzed using a multilevel model. RESULTS: The major cost of the treatment of FB injuries is covered by the ENT Departments, which are usually the first choice of referral, directly from the patients. Children had a mean LOS of 2.13 days (95% C.I. 1.99-2.29). Treatment of the FB was associated with a mean cost of euro 1017.37 (95% C.I. 963.27-1073.51). In the multivariable analysis higher costs are related to the modality of arrival to the hospital by walk, to the site of the injury (ICD-933, ICD-934, ICD-935 in particular) and to the use of surgery in removing the FB. DISCUSSION: Foreign bodies injuries are posing a great threat not only with regards to the clinical aspects but also from the public health perspective, their treatment being associated with high costs, in particular when surgery is needed.

Plasma protein S-antigen (PS:Ag) in selected disease states.

Protein S is a vitamin K-dependent glycoprotein acting as a cofactor for activated protein C and thereby exerting an antithrombotic effect. When compared to values recorded in the 10 healthy normal weight normolipidemic control subjects (80.1% +/- 5.16; mean +/- SEM), plasma protein S-antigen (PS:Ag) level was found to be significantly (p < 0.01) decreased in the 11 patients with decompensated cirrhosis of the liver (54.72% +/- 4.89) and in the 12 surgical patients in critical condition (59.2 +/- 4.96), while obviously (p < 0.001) increased plasma levels were noted in the group including 20 overweight and hyperlipidemic subjects (113% +/- 3.1). Since the low PS:Ag level was associated with a decreased serum cholinesterase (CHE) activity, while both plasma PS:Ag and serum CHE activity were increased in overweight and hyperlipidemic subjects it is considered that impaired or respectively enhanced hepatic protein synthesis is at least partially responsible for changes affecting this antithrombotic plasma protein.

Clinical studies on plasma protein C. Correlation with serum cholinesterase.

When compared to 32 healthy normal weight normolipidemic control subjects, plasma protein C antigen and serum cholinesterase activity were significantly decreased in 17 patients with decompensated cirrhosis of the liver and in 29 critically-ill surgical patients displaying the acute phase reaction, most of them without evidence of consumption coagulopathy. The low levels of these variables are considered to be subsequent to impaired and dysregulated hepatic protein synthesis. On the contrary, plasma protein C and serum cholinesterase were increased in 20 nephrotic patients and in 20 overweight hypertriglyceridemic subjects, a finding highly suggestive of enhanced hepatic synthesis probably related to an accelerated turnover of triglycerides. A discrepancy between low serum cholinesterase activity and normal or even high plasma protein C antigen was noted in 15 patients with cholestasis. This was particularly evident in 7 subjects with extrahepatic cholestasis and an abnormal pattern of hepatic protein synthesis or impaired clearance of plasma protein C would appear to develop in such pathological conditions.