Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma

Purpose: CD19 is a cell surface protein that is found on both healthy and malignant B cells. Accordingly, it has become an important target for novel treatments for non-Hodgkin lymphomas and B-cell leukaemia. Three anti-CD19 monoclonal antibodies with distinct mechanisms of action have been developed for the treatment of B-cell malignancies. Methods: We reviewed the preclinical and clinical data on the development of the newly approved anti-CD19 monoclonal antibodies blinatumomab, tafasitamab and loncastuximab tesirine, and consider their place in the treatment of relapsed or refractory B-cell malignancies. Results: Blinatumomab is a bispecific T-cell engager that binds to both CD19 on B cells and CD3 on T cells, facilitating antibody-dependent cytotoxicity. Blinatumomab significantly prolongs overall survival in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, although cytokine release syndrome and severe neurotoxicity may necessitate discontinuation. Tafasitamab, which has modified anti-CD19 Fab and Fc regions, has significantly enhanced affinity for both CD19 and effector cell receptors compared with unmodified anti-CD19. In L-MIND, tafasitamab plus lenalidomide provided an overall response rate (ORR) of 57.5% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients non-transplant eligible. Loncastuximab tesirine is an antibody–drug conjugate that has been studied as monotherapy and in combination with ibrutinib in 3L + relapsed or refractory DLBCL. The ORR was 48.3% in a phase II trial of loncastuximab tesirine. The optimal place of anti-CD19 monoclonal antibodies in therapy has yet to be determined, but the prospect of improved outcomes for at least some patients with treatment-resistant B-cell malignancies appears likely, particularly in those with limited therapeutic options and poor prognosis

Interpretation of Voltage Measurements in Cutting Torches

Anode-cathode and nozzle-cathode voltages, plenum pressure and gas mass flow measurements in a low current (30 A) cutting torch, operated with oxygen gas, are used as inputs for an electrical model coupled to a simplified fluid model, in order to infer some properties of the plasma-gas structure that are difficult to measure. © 2006 American Institute of Physics.Fil:Kelly, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Minotti, F.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Optical properties of highly n-doped germanium obtained by in situ doping and laser annealing

High n-type doping in germanium is essential for many electronic and optoelectronic applications especially for high performance Ohmic contacts, lasing and mid-infrared plasmonics. We report on the combination of in situ doping and excimer laser annealing to improve the activation of phosphorous in germanium. An activated n-doping concentration of 8.8  ×  1019 cm−3 has been achieved starting from an incorporated phosphorous concentration of 1.1  ×  1020 cm−3. Infrared reflectivity data fitted with a multi-layer Drude model indicate good uniformity over a 350 nm thick layer. Photoluminescence demonstrates clear bandgap narrowing and an increased ratio of direct to indirect bandgap emission confirming the high doping densities achieved

Electrical studies and plasma characterization of an atmospheric pressure plasma jet operated at low frequency

Low-temperature, high-pressure plasma jets have an extensive use in medical and biological applications. Much work has been devoted to study these applications while comparatively fewer studies appear to be directed to the discharge itself. In this work, in order to better understand the kind of electrical discharge and the plasma states existing in those devices, a study of the electrical characteristics of a typical plasma jet, operated at atmospheric pressure, using either air or argon, is reported. It is found that the experimentally determined electrical characteristics are consistent with the model of a thermal arc discharge, with a highly collisional cathode sheet. The only exception is the case of argon at the smallest electrode separation studied, around 1 mm in which case the discharge is better modeled as either a non-thermal arc or a high-pressure glow. Also, variations of the electrical behavior at different gas flow rates are interpreted, consistently with the arc model, in terms of the development of fluid turbulence in the external jet.Fil: Giuliani, Leandro Estanislao. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Xaubet Brea, Magalí Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Grondona, Diana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Minotti, Fernando Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Kelly, Hector Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentin

A five-year survey for plastic surgery malpractice claims in Rome, Italy

(1) Introduction: Medical malpractice claims against both health institutions and physicians are a crucial topic in Italy, as well as in other countries, particularly regarding civil proceedings. Our study reports an analysis of all of the malpractice judgments concerning plastic surgery decided in the Civil Court of Rome between 2012 and 2016. (2) Methods: the database of the Observatory Project on Medical Responsibility (ORMe) was analyzed, which collects all of the judgments of the Civil Court of Rome, that is, the first instance district court. Therefore, neither the jurisprudence of the second level court nor that of the Supreme Court was taken into account. (3) Results: 144 judgments concerning plastic surgery were delivered in the five-year period of 2012–2016 (corresponding to 10.6% of total professional liability verdicts of the Civil Court of Rome in the same period). In 101/144 cases (70.14%), the claim was accepted. A total of €4,727,579.00 was paid in compensation for plastic surgery malpractice claims, with a range from a minimum amount of €1555.96 to a maximum amount of €1,425,155.00 and an average compensation of €46,807.71 per claim that was significantly lower compared to other surgical disciplines. (4) Conclusions: Our data confirm that the analyzed branch has a high litigation rate, with a prevalence of convictions for cosmetic procedures over reconstructive ones, both for malpractice and for violation of the informed consent. Plastic surgery is also confirmed among those branches in which the professionals are more frequently sued compared to health institutions

Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity

Objective: Angiotensin II (Ang II), endothelin-1 (ET-1) and reactive oxygen species (ROS) have been implicated in the development of pathologic changes associated with obesity including hypertension and atherosclerosis. The aim of this study was to investigate the effects of dietary fat content on vasoreactivity and receptor expression at the level of gene and protein expression. Methods: C57BL/6 mice were fed diets of normal (Control, 12.3% kcal from fat), high (HF, 41% kcal from fat) and very high (VHF, 58% kcal from fat) fat content for 15weeks. Glucose tolerance tests were performed, and aortic rings were exposed to ET-1 (0.01-300nM) and Ang II (100nM) in the presence of l-nitro-arginine-methyl ester (l-NAME; 300μM). Gene and protein expressions of angiotensin and endothelin receptors were examined by real-time PCR and immunoblotting, respectively. The effects of diet on responses to acetylcholine (ACh 0.1-300μM), in the absence or presence of l-NAME, and to exogenous ROS/·OH were also investigated. Results: Both high fat diets similarly impaired glucose tolerance (P<0.05). Increasing dietary fat augmented contractions to Ang II in a step-wise manner (P<0.05). Conversely, increasing dietary fat had no effect on contractions to ET-1. Exposure to ROS/·OH resulted in a rapid vasodilation that was markedly augmented in a step-wise manner with increasing dietary fat (P<0.05). Endothelium-dependent relaxation to ACh was unaffected whereas vasoconstriction to high concentrations of ACh was enhanced in VHF animals (P<0.05 vs. control). Gene expression of the AT1B receptor was increased in the aorta of VHF mice, and aortic ETA receptor protein expression was increased after both high fat diets. Conclusions: These findings demonstrate that changes in dietary fat intake modulate vascular reactivity in response to Ang II and ROS, as well as expression of vascular angiotensin and endothelin receptors. Dietary fat intake may thereby directly affect cardiovascular ris

Investigation of the relevant kinetic processes in the initial stage of a double-arcing instability in oxygen plasmas

A numerical investigation of the kinetic processes in the initial (nanosecond range) stage of the double-arcing instability was developed. The plasma-sheath boundary region of an oxygen-operated cutting torch was considered. The energy balance and chemistry processes in the discharge were described. It is shown that the double-arcing instability is a sudden transition from a diffuse (glow-like) discharge to a constricted (arc-like) discharge in the plasma-sheath boundary region arising from a field-emission instability. A critical electric field value of ∼10^7 V/m was found at the cathodic part of the nozzle wall under the conditions considered. The field-emission instability drives in turn a fast electronic-to-translational energy relaxation mechanism, giving rise to a very fast gas heating rate of at least ∼10^9 K/s, mainly due to reactions of preliminary dissociation of oxygen molecules via the highly excited electronic state O2(B^3) populated by electron impact. It is expected that this fast oxygen heating rate further stimulates the discharge contraction through the thermal instability mechanism.Fil: Mancinelli, Beatriz Rosa. Universidad Tecnológica Nacional. Facultad Regional Venado Tuerto; ArgentinaFil: Prevosto, Leandro. Universidad Tecnológica Nacional. Facultad Regional Venado Tuerto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Chamorro Garcés, Juan Camilo. Universidad Tecnológica Nacional. Facultad Regional Venado Tuerto; ArgentinaFil: Minotti, Fernando Oscar. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kelly, Hector Juan. Universidad Tecnológica Nacional. Facultad Regional Venado Tuerto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentin

Trielectrode plasma reactor for water treatment

Water pollution due to emerging organic pollutants, such as agrochemicals, has become a topic of growing interest worldwide. The increase of pollutants in aquatic systems stimulated the development of new strategies for water remediation. Plasma technology is an advanced oxidation process which has proved to be an efficient method for organic matter degradation. In this work, a novel design of a trielectrode plasma reactor based on a dielectric barrier discharge extended to a third electrode operated in ambient air is presented. The water to be treated flows through a gutter with low impedance and far from the electrodes connected to the voltage sources. The reactor operates in ambient air, and it does not rely on the use of expensive inert gases. The design of the reactor is easily scalable. The performance of the reactor, in terms of the removal efficiency and the energy yield, was tested in an aqueous solution of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), one of the most widely used around the world. The reactor presents a good efficiency in the removal of the herbicide 2,4-D and values of energy yield of about 240 mg/kW h.Fil: Giuliani, Leandro Estanislao. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: De Angelis, L.. Instituto Tecnológico de Buenos Aires; ArgentinaFil: Díaz Bukvic, Gema. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zanini, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Minotti, Fernando Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Errea, María Inés. Instituto Tecnológico de Buenos Aires; ArgentinaFil: Grondona, Diana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentin

Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease-free survival of surgically resected non-small-cell-lung cancer patients

BACKGROUND: Insulin-like growth factor 1 receptor (IGF1R) represents a novel molecular target in non-small-cell-lung cancer (NSCLC). IGF1R and epidermal growth factor receptor (EGFR) activation are essential to mediate tumor cell survival, proliferation, and invasion. This study investigates the prognostic role of IGF1R and EGFR in surgically resected NSCLC. MATERIALS AND METHODS: IGF1R and EGFR copy number gain (CNG) were tested by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC) in 125 stage I-II-IIIA NSCLC patients. RESULTS: Fourty-six tumors (40.3 %) were IGF1R FISH-positive (FISH+), and 76 (67.2 %) were EGFR FISH+. Tumors with concomitant IGF1R/EGFR FISH+ were observed in 34 cases (30.1 %). IGF1R and EGFR FISH+ were associated with SCC histology (p = 0.01 and p = 0.04, respectively). IGF1R and EGFR protein over-expression (IHC+) were detected in 45 (36.0 %) and 69 (55.2 %) cases, respectively. Tumors with concomitant IGF1R/EGFR IHC+ were detected in 31 (24.8 %) patients. IGF1R/EGFR FISH+ and IGF1R/EGFR IHC+ were significantly associated (χ(2) = 4.02, p = 0.04). Patients with IGF1R/EGFR FISH+ and IGF1R/EGFR IHC+ were associated with shorter disease-free survival (DFS) (p = 0.05 and p = 0.05, respectively). Patients with concomitant IGF1R/EGFR FISH+/IHC+ had a worse DFS and overall survival (p = 0.005 and p = 0.01, respectively). The multivariate model confirmed that IGF1R/EGFR FISH+/IHC+ (hazard ratio (HR), 4.08; p = 0.01) and tumor stage (II-III vs I) (HR, 4.77; p = 0.003) were significantly associated with worse DFS. CONCLUSIONS: IGF1R/EGFR FISH+ correlates with IGF1R/EGFR IHC+. IGF1R/EGFR FISH+/IHC+ is an independent negative prognostic factor for DFS in early NSCLC. These features may have important implications for future anti-IGF1R therapeutic approaches