Rapid protocol for irinotecan desensitization: a case report and literature review

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Measurement of the thermal expansion coefficient of an Al-Mg alloy at ultra-low temperatures

We describe a result coming from an experiment based on an Al-Mg alloy (~ 5% Mg) suspended bar hit by an electron beam and operated above and below the termperature of transition from superconducting to normal state of the material. The amplitude of the bar first longitudinal mode of oscillation, excited by the beam interacting with the bulk, and the energy deposited by the beam in the bar are the quantities measured by the experiment. These quantities, inserted in the equations describing the mechanism of the mode excitation and complemented by an independent measurement of the specific heat, allow us to determine the linear expansion coefficient of the material.Comment: 13 pages, 4 figure

Allergic reactions to midazolam: A case series from an Italian allergy unit.

Midazolam is a short-acting benzodiazepine with central nervous system depressing action, commonly used for conscious sedation for various procedures and for its pharmacologic properties. In literature, severe adverse reactions to this drug are described, but only in few cases positive allergological tests were demonstrated. The authors collected herein five clinical cases of different allergic reactions to midazolam demonstrated by positive skin tests. The 1° case is a suspected Kounis syndrome with cardiorespiratory arrest during an elective video laparoscopic cholecystectomy. The 2° and 5° cases are two systemic reactions with involvement of the skin and the gastrointestinal/respiratory system during elective surgeries in two patients with clinical history of atopia, while the 3° and 4° cases are local skin reactions in correspondence with the infusion site of midazolam during the execution of a colonoscopy. All the patients performed a complete allergological evaluation for the reaction involved drugs. In all cases, only the intradermal test (IDT) with midazolam at 0.5 mg/mL was positive.Allergological tests performed in 10 healthy controls with negative results supported the diagnosis. Therefore, midazolam is often considered a safe drug, because it does not have any active metabolites, in rare cases, it could cause different types of allergic adverse reactions: from severe anaphylaxis with cardiorespiratory arrest to simple local skin reactions. Skin tests remain the first line in the diagnosis of an immediate-type hypersensitivity to midazolam; even if they could lose in sensitivity with increasing latency from the event. However the concentrations recommended by current guidelines of European Network for Drug Allergy (ENDA) and the European Academy of Allergy and Clinical Immunology (EAACI) drug allergy interest groups might not rule out some false-positive reactions due to an irritant effect that should be considered. In doubt cases, other allergological or laboratory tests (i.e., basophil activation tests, serum tryptase, or provocation tests) remain useful to support the diagnosis of an IgE-mediated reaction. Midazolam associated anaphylaxis is relatively rare and the risk factors associated with this event are actually unknown; however, it remains important to obtain a detailed allergic history and each surgical/endoscopic examination unit should be prepared to handle any situation or emergency that may occur

RF Design of the X-band Linac for the EuPRAXIA@SPARC_LAB Project

We illustrate the RF design of the X-band linac for the upgrade of the SPARC_LAB facility at INFN-LNF (EuPRAXIA@SPARC_LAB). The structures are travelling wave (TW) cavities, working on the 2π/3 mode, fed by klystrons with pulse compressor systems. The tapering of the cells along the structure and the cell profiles have been optimized to maximize the effective shunt impedance keeping under control the maximum value of the modified Poynting vector, while the couplers have been designed to have a symmetric feeding and a reduced pulsed heating. In the paper we also present the RF power distribution layout of the accelerating module and a preliminary mechanical design

A primary luminal/HER2 negative breast cancer patient with mismatch repair deficiency

: Here, we present the case of a 47-year-old woman diagnosed with luminal B breast cancer subtype and provide an in-depth analysis of her gene mutations, chromosomal alterations, mRNA and protein expression changes. We found a point mutation in the FGFR2 gene, which is potentially hyper-activating the receptor function, along with over-expression of its ligand FGF20 due to genomic amplification. The patient also harbors somatic and germline mutations in some mismatch repair (MMR) genes, with a strong MMR mutational signature. The patient displays high microsatellite instability (MSI) and tumor mutational burden (TMB) status and increased levels of CTLA-4 and PD-1 expression. Altogether, these data strongly implicate that aberrant FGFR signaling, and defective MMR system might be involved in the development of this breast tumor. In addition, high MSI and TMB in the context of CTLA-4 and PD-L1 positivity, suggest the potential benefit of immune checkpoint inhibitors. Accurate characterization of molecular subtypes, based on gene mutational and expression profiling analyses, will be certainly helpful for individualized treatment and targeted therapy of breast cancer patients, especially for those subtypes with adverse outcome

A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient

: Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy