metronomic administration of pegylated liposomal doxorubicin in extensively pre treated metastatic breast cancer patients a mono institutional case series report

Abstract Background Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. Pegylated liposomal-doxorubicin (PLD) pharmacokinetic characteristics support the rationale for using the drug in a metronomic fashion, potentially able to combine anthracyclines efficacy to a low toxicity profile. Patients and methods In a case-series report carried out in both anthracycline-naive and pre-treated metastatic breast cancer patients, we tested feasibility, clinical efficacy and tolerability of PLD administered with a novel metronomic schedule of 20 mg/m2 i.v. every two weeks. Results 52 patients were enrolled and 45 were evaluated. Forty-four patients were assessed for either response or toxicity. Eight patients (18%) had partial responses (PR) and 17 (39%) stable disease (SD), with a clinical benefit (CB) of 45% (95% CI: 30.3%–59.7%). Nineteen patients (43%) had progressive disease (PD). Neither grade 3 nor grade 4 haematological or clinical side effects were recorded, except for 2 patients with grade 3 palmar-plantar erythrodysesthesia (PPE). No cardiac toxicity was recorded. Conclusion Metronomic administration of PLD is a feasible and active treatment for extensively pre-treated metastatic breast cancer patients, alternative to classic anthracyclines, balancing clinical efficacy with a good quality of life in terms of reduced side effects and low personal costs for the patient

Core Biopsies from Prostate Cancer Patients in Active Surveillance Protocols Harbor PTEN and MYC Alterations

Background: Genomic characterization of prostate cancer (PCa) biopsies may improve criteria for the selection of patients suitable for active surveillance (AS). Objective: To identify somatic genomic aberrations associated with adverse outcome as AS protocol exclusion indicators. Design, setting and participants: Whole-exome sequencing profiles were generated for Gleason score (GS) = 3 + 3 biopsies obtained from 54 PCa patients enrolled in two AS protocols. Patients were selected as representative of a nonindolent population, consisting of 27 patients who dropped out from AS due to upgrading (ie, finding of GS > 3 + 3 at a follow-up biopsy) within 2 yr, and a potentially indolent population, consisting of 27 patients in AS for 654 yr without any evidence of reclassification. Outcome measurements and statistical analysis: The genomic alteration landscape of core biopsies was analyzed using an integrated computational pipeline and correlated with patient reclassification due to upgrading. Results and limitations: Of all the GS = 3 + 3 biopsies of the study cohort, 34% showed clear evidence of somatic copy number aberrations along the genome. Of these, 39% came from the potentially indolent and 61% from the nonindolent population. Single-nucleotide variants demonstrated low allelic fractions and included a common F133C mutation in the SPOP gene. The minimally altered genomic landscape of the study cohort presented a distinct set of monoallelic deletions, including on 8p, 13q, 16q, and 21q, and rare amplifications of 8q, which were observed in both AS patient populations. Concerning lesions typically associated with adverse outcome, PTEN deletions and MYC amplification, though observed in a small number of cases, were detected exclusively or preferentially, respectively, in nonindolent patients. Such molecular findings were confirmed by immunohistochemistry on the same tissue blocks. The small sample size and the retrospective nature of the analysis represent the main study limitations. Conclusions: Genomic features enriched in aggressive tumors can be detected in GS = 3 + 3 core biopsies of AS patients. Patient summary: PTEN and MYC alterations at the time of diagnosis would deserve investigation in larger cohorts of AS patients to assess their potential as biomarkers for a more precise/earlier identification of patients at risk of reclassification. The presence of adverse outcome-related genomic lesions, such as PTEN deletion and MYC amplification, in GPS = 3 + 3 diagnostic core biopsies of prostate cancer patients could be considered for a more precise/earlier selection of patients not suitable for active surveillance

Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients : a feasibility study

Background: Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300\uc2\ua0mmHg. In all patients, under constant tidal volume (6\ue2\u80\u938\uc2\ua0ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10\uc2\ua0min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2\uc2\ua0cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT). Results: The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13\uc2\ua0\uc2\ub1\uc2\ua03 vs. 9\uc2\ua0\uc2\ub1\uc2\ua02\uc2\ua0cmH2O, p\uc2\ua0<\uc2\ua00.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers. Conclusions: In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment

The dramatic COVID-19 outbreak in italy is responsible of a huge drop in urological surgical activity: A multicenter observational study

OBJECTIVE: Italy is facing the COVID-19 outbreak with an abrupt reorganization of its national health-system, in order to augment care provision to symptomatic patients. The sudden shift of personnel and resources towards COVID-19 care has led to the reduction of surgery, with possible severe drawbacks. The aim of the study is to describe the trend in surgical volume in urology, in Italy. MATERIALS AND METHODS: Thirty-three urological units with physicians affiliated to the AGILE consortium were involved in a survey. Urologists were asked to report the amount of surgical elective procedures week-by-week, from the beginning of the emergency to the following month. RESULTS: The 33 hospitals involved in the study account, globally, for 22,945 beds and are distributed in 13/20 Italian regions. Before the outbreak, the involved urology units performed an overall amount of 1,213 procedures per week, half of which were oncological. One month later, the amount of surgery declined by 78%. Lombardy, the first region with positive-cases, experienced a 94% reduction. The decrease in oncological and non-oncological surgical activity was 35,9% and 89%, respectively. The trend of the decline showed a delay of roughly 2 weeks for the other regions. CONCLUSION: Italy, the country with the highest fatality rate from COVID-19, is experiencing a sudden decline in surgical activity. It is inversely related to the increase in COVID-19 care, with potential harm particularly in the oncological field. The Italian experience can be helpful for future surgical pre-planning in other countries not so hardly hit by the disease yet

FuturAP - Rapporto sul Futuro e l'innovazione dell'Amministrazione Pubblica

Il volume raccoglie e analizza i principali fattori di cambiamento e innovazione dell'Amministrazione Pubblica italiana attorno a 5 macro-tematiche: Etica, trasparenza e protezione dati; innovazione resiliente; performance e capitale umano; enti locali e sfide globali; welfare sostenibil

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Probing athletics tracks degradation using a microscratch technique

Continuous outdoor exposure of athletics tracks can lead to an important degradation of their mechanical and aesthetical properties. In this work, flat laboratory samples prepared from rubber blends of different colours were subjected to natural and artificial ageing, to investigate their effect on the surface properties. Compositional variations demonstrated a generalized oxidization of the outer (top) material layer, together with surfacing of inorganic additives; a small increase of the degradation temperature of the natural rubber component was reported, similar to the one previously observed on bulk track samples. The smooth surface of the present samples allowed their testing using a microscratching technique, able to mechanically probe the material within a few hundred microns below the top surface. The formation of a significantly harder outer crust layer was reported, potentially impacting the track performance since it is exactly the locus of interaction between the athlete and the sport surface. In particular, the increase in scratch hardness is accompanied by a significant reduction in the apparent friction coefficient. These surface modifications, previously unreported in the literature, are independent phenomena with respect to generalized bulk ageing. Microscratch data supported by microscopy evidenced a significantly varying sensitivity to ageing for the different colours (red, blue, green, neutral). Moreover, this sensitivity appeared strongly dependent on the applied ageing protocol (natural vs. artificial). In view of these results, care must be taken when accelerated artificial weathering is used to simulate long-term natural ageing of these materials

Teoría crítica, izquierda y políticas públicas de Comunicación: el caso de América Latina y los gobiernos progresistas

Este trabajo analiza la evolución de las políticas de Comunicación en la agenda pública latinoamericana. Se focaliza en el estudio de países cuyos gobiernos se han proclamado a sí mismos como de izquierda o progresistas, en un intento por encontrar tendencias comunes en los procesos de implementación de sus políticas públicas. This paper points to identify the emergence of communication policies as a relevant item on the public agenda of Latin America. We focus on those countries whose governments have proclaimed themselves to be leftist or progressive, in an attempt to map common trends, objectives and implementations of public communication policies