Impressive long-term response with pertuzumab and trastuzumab in HER2-positive breast cancer with brain metastasis

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial disease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months

LISA Pathfinder test-mass charging during galactic cosmic-ray flux short-term variations

none5sìMetal free-floating test masses aboard the future interferometers devoted to gravitational wave detection in space are charged by galactic and solar cosmic rays with energies > 100 MeV/n. This process represents one of the main sources of noise in the lowest frequency band (< 10(-3) Hz) of these experiments. We study here the charging of the LISA Pathfinder (LISA-PF) gold-platinum test masses due to galactic cosmic-ray (GCR) protons and helium nuclei with the Fluka Monte Carlo toolkit. Projections of the energy spectra of GCRs during the LISA-PF operations in 2015 are considered. This work was carried out on the basis of the solar activity level and solar polarity epoch expected for LISA-PF. The effects of GCR short-term variations are evaluated here for the first time. Classical Forbush decreases, GCR variations induced by the Sun rotation, and fluctuations in the LISA-PF frequency bandwidth are discussed.Article Number: 035001openGrimani, Catia; Fabi, M.; Lobo, A.; Mateos, I.; Telloni, D.Grimani, Catia; Fabi, M.; Lobo, A.; Mateos, I.; Telloni, D

insights into the effects of occupant behaviour lifestyles and building automation on building energy use

Abstract In order to optimize building energy consumption, Member States will have to establish minimum efficiency requirements for systems, and promote the introduction of active control system in new constructions or major renovations. Energy saving, plant efficiency and environmental sustainability are also factors delineating smart buildings. Interestingly, occupant behaviour is known to be one of the key sources of uncertainty in the prediction of building energy use. The success of automation strategies is recognized to be dependent on how the occupants interact with the building. The present research describes the effect of different building occupants' lifestyles and building automation on a high performing building

Occupant behaviour lifestyles and effects on building energy use: Investigation on high and low performing building features

Occupant behaviour is known to be one of the key sources of uncertainty in the prediction of building energy use. Extended literature reviews linked the large performance gaps between residential buildings with same properties and similar climate conditions to the way occupants interact with the building envelope and systems. Furthermore, in the last decades, more stringent energy codes have led to energy efficient design strategies with the aim of reaching the nearly-zero energy target. The success of these strategies is now heavily dependent on how the occupants interact with the building, or rather, on the energy-related lifestyles they assume. In line with this, the present study employs building simulations to demonstrate the potential impact of different occupant behaviour lifestyles on the energy use of a Mediterranean (i) residential nearly-zero energy building (nZEB) under-construction and a (ii) Reference Building (RB) whose envelope-driven loads dominate the consumption profile

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

COX-2 targeting in cancer: a new beginning?

Cyclo-oxygenase-2 (COX-2), the inducible enzyme catalyzing the rate-limiting step in the conversion of arachidonic acid into eicosanoids, is overexpressed in a wide variety of malignancies and associates with poor prognostic features [1]. Consequently, selective COX-2 inhibitors have been explored as therapeutic or chemopreventive agents in different settings; however, initial enthusiasm was tempered by reports of substantial gastrointestinal toxicity as well as of increased cardiovascular risk, mostly coming from postmarketing use as anti-inflammatory drugs and Cancer Research Campaign (UK) chemoprevention trials and eventually resulting in the withdrawal of rofecoxib from the market [2]

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy

Exploring Factors Influencing Changes in Incidence and Severity of Multisystem Inflammatory Syndrome in Children

Multisystem inflammatory syndrome (MIS-C) is a rare condition associated with COVID-19 affecting children, characterized by severe and aberrant systemic inflammation leading to nonspecific symptoms, such as gastrointestinal, cardiac, respiratory, hematological, and neurological disorders. In the last year, we have experienced a progressive reduction in the incidence and severity of MIS-C, reflecting the worldwide trend. Thus, starting from the overall trend in the disease in different continents, we reviewed the literature, hypothesizing the potential influencing factors contributing to the reduction in cases and the severity of MIS-C, particularly the vaccination campaign, the spread of different SARS-CoV-2 variants (VOCs), and the changes in human immunological response. The decrease in the severity of MIS-C and its incidence seem to be related to a combination of different factors rather than a single cause. Maturation of an immunological memory to SARS-CoV-2 over time, the implication of mutations of key amino acids of S protein in VOCs, and the overall immune response elicited by vaccination over the loss of neutralization of vaccines to VOCs seem to play an important role in this change

Gut Microbiota Dysbiosis in Childhood Vasculitis: A Perspective Comparative Pilot Study

Kawasaki disease (KD) and Henoch–Schönlein purpura (HSP) are the most frequent vasculitis in childhood. For both, a multifactorial mechanism has been hypothesised, with an abnormal immune response in genetically predisposed children. Gut microbiota (GM) alterations might trigger the hyperimmune reaction. Our aim was to explore the GM in KD and compare it with the GM of HSP and febrile children. Children diagnosed with KD, HSP and non-KD febrile illness (F) were enrolled. GM was profiled by 16S rRNA gene sequencing and compared with the profiles of healthy children from previous studies. We enrolled 13 KD, 10 HSP and 12 F children. Their GM significantly differed from controls, with an overall reduction in the relative abundance of beneficial taxa belonging to the Ruminococcaceae and Lachnospiraceae families. Potential KD and HSP signatures were identified, including smaller amounts of Dialister in the former, and Clostridium and Akkermansia in the latter. Notably, the GM structures of KD, HSP and F patients stratified by abdominal involvement, with more severe dysbiosis in those suffering from intestinal symptoms. This is the first study analysing GM in a mostly Caucasian cohort of KD and HSP children. Our data could open up new opportunities for childhood vasculitis treatment