Enhanced Photoluminescence with Dielectric Nanostructures: A review

Abstract Resonant dielectric subwavelength structures made of high-refractive-index materials are an emerging powerful platform with unique advantages compared to plasmonic based nanostructures. Owing to the low ohmic losses, to their ability to localize optical near-field at nanoscale, and exciting both electric and magnetic resonant modes, high-index dielectric materials are being used in various applications. Starting from the first principles, we aim at showing how resonant dielectric nanostructures can be efficiently used to enhance photoluminescence signal from an excited molecule, and we review the most recent results present in the Literature

Time for Dynamic Assessment of Fitness in Acute Myeloid Leukemia

Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...

Thickness-dependent crystallization on thermal anneal for titania/silica nm-layer composites deposited by ion beam sputter method.

Crystallization following thermal annealing of thin film stacks consisting of alternating nm-thick titania/silica layers was investigated. Several prototypes were designed, featuring a different number of titania/silica layer pairs, and different thicknesses (in the range from 4 to 40 nm, for the titania layers), but the same nominal refractive index (2.09) and optical thickness (a quarter of wavelength at 1064 nm). The prototypes were deposited by ion beam sputtering on silicon substrates. All prototypes were found to be amorphous as-deposited. Thermal annealing in air at progressive temperatures was subsequently performed. It was found that the titania layers eventually crystallized forming the anatase phase, while the silica layers remained always amorphous. However, progressively thinner layers exhibited progressively higher threshold temperatures for crystallization onset. Accordingly it can be expected that composites with thinner layers will be able to sustain higher annealing temperatures without crystallizing, and likely yielding better optical and mechanical properties for advanced coatings application. These results open the way to the use of materials like titania and hafnia, that crystallize easily under thermal anneal, but ARE otherwise promising candidate materials for HR coatings necessary for cryogenic 3rd generation laser interferometric gravitational wave detectors

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50x10e9/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (>2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis

Case report: A Saprochaete clavata (Magnusiomyces clavatus) severe infection effectively treated with granulocyte transfusion in a young patient with myeloid sarcoma

Myeloid sarcoma is a hematologic malignancy consisting of extramedullary tissue involvement by myeloid blasts, usually considered as acute myeloid leukemia and treated accordingly. The disease itself, together with chemotherapy and disease-associated factors, may have an impact in increasing the risk of developing severe and frequently life-threatening infections. Herein, we describe the case of a patient with a right breast skin lesion, histologically diagnosed myeloid sarcoma, who developed a severe disseminated fungal infection by Saprochaete clavata (Magnusiomyces clavatus), during the first consolidation course of chemotherapy. Despite maximum antifungal therapy, the infection progressed and the fungus continued to be isolated until granulocyte transfusion therapy was initiated. Our experience suggests that patients with profound and long-lasting neutropenia could benefit from granulocyte transfusions as additional therapy in severe fungal infections resistant to broad-spectrum antimicrobial therapy

Pulmonary function testing for fitness assessment in asymptomatic adults with newly diagnosed acute myeloid leukemia

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Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal postremission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint

Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells

<p>Abstract</p> <p>Background</p> <p>ZAP-70 is an independent negative prognostic marker in chronic lymphocytic leukemia (CLL). Usually, its expression is investigated by flow cytometric protocols in which the percentage of ZAP-70 positive CLL cells is determined in respect to isotypic control (ISO-method) or residual ZAP-70 positive T cells (T-method). These methods, however, beside suffering of an inherent subjectivity in their application, may give discordant results in some cases. The aim of this study was to assess the prognostic significance of these methods in comparison with another in which ZAP-70 expression was evaluated as a Mean-Fluorescence-Intensity Ratio between gated T and CLL cells (T/B Ratio-method).</p> <p>Methods</p> <p>Cytometric files relative to ZAP-70 determination according to the three readouts were retrospectively reviewed on a cohort of 173 patients (test set), all with complete clinical and biological prognostic assessment and time-to-treatment (TTT) available. Findings were then validated in an independent cohort of 341 cases from a different institution (validation set).</p> <p>Results</p> <p>The optimal prognostic cut-offs for ZAP-70 expression were selected at 11% (ISO-method) or 20% of positive cells (T-method), as well as at 3.0 (T/B Ratio-method) in the test set; these cut-offs yielded 66, 60 and 73 ZAP-70⁺cases, respectively. Univariate analyses resulted in a better separation of ZAP-70⁺vs. ZAP-70^-CLL patients utilizing the T/B Ratio, compared to T- or ISO-methods. In multivariate analyses which included the major clinical and biological prognostic markers for CLL, the prognostic impact of ZAP-70 appeared stronger when the T/B-Ratio method was applied. These findings were confirmed in the validation set, in which ZAP-70 expression, evaluated by the T- (cut-off = 20%) or T/B Ratio- (cut-off = 3.0) methods, yielded 180 or 127 ZAP-70⁺cases, respectively. ZAP-70⁺patients according to the T/B Ratio-method had shorter TTT, both if compared to ZAP-70^-CLL, and to cases classified ZAP-70⁺by the T-method only.</p> <p>Conclusions</p> <p>We suggest to evaluate ZAP-70 expression in routine settings using the T/B Ratio-method, given the operator and laboratory independent feature of this approach. We propose the 3.0 T/B Ratio value as optimal cut-off to discriminate ZAP-70⁺(T/B Ratio less than 3.0) from ZAP-70^-(T/B Ratio more/equal than 3.0) cases.</p

Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial

Using a multiparametric flow cytometry (MFC) assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients affected with Acute Myeloid Leukemia (AML). This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined MRD threshold of 0.035% bone marrow residual leukemic cell (RLC) calculated on mononuclear cells, 154 (59%) were negative (MRD&lt;0.035%) and 107 (41%) were positive (MRD≥0.035%). Using LOD and LOQ, we selected the following categories of patients: 1) LODneg if RLC were below LOD (74; 28.4%); 2) LODpos-LOQneg if RLC were between LOD and LOQ (43; 16.5%); and 3) LOQpos if RLC were above LOQ (144; 54.4%). Two-year overall survival (OS) of these 3 categories was 75.4% vs. 79.8% vs. 66.4%, respectively (p=0.1197). Due to superimposable outcome, LODneg and LODpos-LOQneg categories were combined. Two-year OS of LODneg/LODpos- LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). Such a figure was challenged in multivariate analysis (p=0.048, HR 0.628, 95% CI 0.396-0.997) that confirmed the independent role of LOD-LOQ approach in influencing OS. In the AML1310 protocol, using the threshold of 0.035%, 2-year OS of MRD&lt;0.035% and MRD≥0.035% patients was 74.5% vs. 66.4%, respectively (p=0.3521). In conclusion, the use of LOD-LOQ method results in a more sensitive detection of MRD that, in turn, translates in a more accurate recognition of patients with different outcome

Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation