Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup. METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722). RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6). CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer.

OBJECTIVE: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients. METHODS: WGD was estimated from copy numbers derived from whole-exome sequencing (WES) data of matched tumor and normal DNA from 833 Danish CRC patients. To explore if tumor WGD status impacts ctDNA detection, we applied tumor-informed ctDNA analysis to preoperative plasma samples from all patients. RESULTS: Patients with WGD+ tumors had 53% increased odds of being ctDNA positive (OR = 1.53, 95%CI: 1.12-2.09). After stratification for UICC stage, the association persisted for Stage I (OR = 2.44, 95%CI: 1.22-5.03) and Stage II (OR = 1.76, 95%CI: 1.11-2.81) but not for Stage III (OR = 0.83, 95%CI: 0.44-1.53) patients. CONCLUSION: The presence of WGD significantly increases the probability of detecting ctDNA, particularly for early-stage disease. In patients with more advanced disease, the benefit of WGD on ctDNA detection is less pronounced, consistent with increased DNA shedding from these tumors, making ctDNA detection less dependent on the amount of ctDNA released per tumor cell.

Maximizing the forward scattering of dielectric nanoantennas through surface impedance coatings.

In this Letter, we discuss a novel, to the best of our knowledge, approach for designing passive nanoantennas with maximum forward and almost-zero backward scattering. The proposed approach is based on the use of high-index dielectric spheres supporting dipolar magnetic resonances, which are coated by ultra-thin surface impedance coatings. It is shown that, by properly engineering the radius of the coat and its surface reactance, it is possible to introduce an additional electric dipolar resonance and to make this overlap with the magnetic one sustained by the high-index dielectric sphere. A realistic design that is based on graphene and works in the low-THz range is also proposed and verified with full-wave simulations. Compared to earlier techniques based on the combination of multipoles or on the use of ellipsoidal particles, the proposed one is quite robust toward realistic ohmic losses and preserves the isotropic behavior of the nanoantenna.

Narrowband transparent absorbers based on ellipsoidal nanoparticles.

In this paper, we propose the design of an optical device that is able to selectively absorb impinging light in a desired frequency range while being almost completely transparent outside this range. The proposed absorber is a variant of the optical Salisbury screen we recently proposed [Opt. Lett.41, 3383 (2016)OPLEDP0146-959210.1364/OL.41.003383] but, differently from this earlier version, is transparent for any electromagnetic wave whose frequency is outside the absorption spectrum. Such an absorber also exhibits excellent performance in terms of angular bandwidth and may find application in all scenarios where narrowband absorption is required, such as for light filters or digital sensors. Full-wave simulations confirming the effectiveness of the proposed absorber as well as its robustness toward geometrical defects are provided.

Exploiting the surface dispersion of nanoparticles to design optical-resistive sheets and Salisbury absorbers.

In this Letter, we propose a method to implement resistive sheets exhibiting a desired value of the intrinsic surface resistance at optical frequencies. Considering the sheet made by arrays of plasmonic nanoparticles, the idea is to tailor the surface dispersion occurring when the dimensions of the nanoparticles are smaller than the mean free path of electrons in the constituent material. An analytical model of the surface resistance is proposed and its effectiveness assessed through full-wave simulations. Finally, the applicability of the proposed resistive sheets to implement optical Salisbury screens is discussed and validated through full-wave simulations.

[The overuse of thromboprophylaxis in medical patients: main clinical aspects]. / L'uso eccessivo della tromboprofilassi in pazienti medici: i principali aspetti clinici.

BACKGROUND: Overuse of thromboprophylaxis is not an infrequent behavior in internal medicine. However, differently from underuse, overuse of thromboprophylaxis is rarely taken into account, and only few studies have addressed this issue. The purpose of our study was to try to understand the reasons behind this phenomenon. METHODS: Using data from the TEVERE study, we evaluated 279 patients hospitalized in 21 hospitals of the Lazio Region in Italy. Only patients who were negative to major risk scores as established in the scientific literature were included. We assessed the frequency of thromboprophylaxis in acutely ill medical patients hospitalized in emergency and internal medicine wards, and we performed a comparative analysis for each risk factor among patients who received or not received thromboprophylaxis. RESULTS: Forty-seven patients (16.5%) with negative risk scores were given thromboprophylaxis during hospitalization. On backward stepwise logistic regression analysis, severe infection (odds ratio [OR] 2.31; 95% confidence interval [CI] 1.25-4.35) and chronic venous insufficiency (OR 3.02; 95% CI 1.96-4.67) were found to be the strongest predictors of the use of thromboprophylactic treatment with heparin. The subgroup of patients who did not exhibit risk factors was also analyzed, and age was found to be the main factor in the decision-making process regarding heparin administration in the absence of other risk factors (74.9 ± 11.8 vs 63.7 ± 18.1, p=0.002). CONCLUSIONS: Our findings suggest that thromboprophylaxis is associated with considerable uncertainty, which results in its overuse. Further research is needed to better understand thromboembolic risk factors in hospitalized medical patients.

Correlation between epicardial fat and cigarette smoking: CT imaging in patients with metabolic syndrome.

BACKGROUND: The aim of our study was to assess the relationship between cigarette smoking and epicardial fat in a cohort of patients with metabolic syndrome (MetS) at risk for coronary artery disease. METHODS: We studied, in primary prevention, 54 subjects diagnosed with MetS. According to their smoking habits, the subjects were divided into two groups: smokers and non-smokers. Besides anthropometric characterization and screening laboratory tests, the subjects had a multidetector computerized tomography scan, which allowed epicardial fat quantification and calcium score (CS) evaluation. RESULTS: Compared with non-smokers, smokers showed older age (61.6 ± 1.8 vs 56.8 ± 1.2 yrs; p < 0.05). Also, the smokers displayed increased epicardial fat volume (138 [123; 150] vs 101[79; 130] ml; p < 0.01) as well as higher CS (94 [3; 301.5] vs 0 [0;10.2]; p < 0.001), in comparison with non-smokers. Notably, CS was positively correlated with smoking habit (rs 0.469; p < 0.01), epicardial fat (rs 0.377; p < 0.01), age (rs 0.502; p < 0.001) and uric acid (rs 0.498; p < 0.01). Accordingly, the associations between both CS or epicardial fat and cigarette smoking were still maintained after adjustment for age (r 0.317; p < 0.05; r 0.427; p < 0.01). Finally, multiple regression analysis showed that smoke was the variable that best predicted CS (R(2) 0.131; ß 0.362; p < 0.05) and epicardial fat (R(2) 0.177; ß 0.453; p = 0.01). CONCLUSIONS: Our findings suggest that, in subjects with MetS, cigarette smoking is an independent predictor of increased epicardial fat volume and higher CS.

Optical cloaking of cylindrical objects by using covers made of core-shell nanoparticles.

In this Letter, we propose an engineered design of optical cloaks based on the scattering cancellation technique and intended to reduce the observability of cylindrical objects. The cover, consisting of a periodic arrangement of core-shell nanospheres, is designed in such a way to exhibit near-zero values of the real part of the homogenized effective permittivity at optical frequencies. Full-wave numerical simulations, considering the measured data of the dielectric function of the plasmonic material composing the shell, show that the cloak is able to reduce by about 6 dB the scattering cross section of a finite-length cylinder at around 740 THz with a -3 dB fractional bandwidth of about 7%. We show also that this result is not significantly affected by the perturbation of the periodic alignment of the core-shell nanospheres, due to possible fabrication issues or to an amorphous arrangement.