Bevacizumab for advanced ovarian cancer treatment. A GRADE based approach

Background: in advanced ovarian cancer, over the last 10 years no studies have demonstrated more appropriate therapeutic options compared to the current standard Carboplatin-Paclitaxel (Cb-P) regimen. Two phase III randomized studies (GOG-218 36 and ICON-7 37) have recently demonstrated the efficacy of bevacizumab (recombinant monoclonal antibody that binds with a high affinity to VEGF-A) in adjunct to Cb-P, with 12-15 months maintenance treatment. Methods: the quality of evidence provided was assessed by the use of the GRADE method. Each outcome (deemed to be essential for the purpose of evaluation of the intervention) was assessed to express the degree of confidence in the entity of the beneficial and/or harmful effects of the intervention. Thus, limitations in the quality of conducting the studies (risk of bias), direct applicability/relevance of results to the target population, and precision of results were taken into account. Results: the GOG-218 and the ICON7 study (high-risk subgroup) demonstrated with MODERATE confidence an improvement in critical outcomes PFS and OS, with an absolute reduction of 96 (GOG-218) – 103 (ICON-7) episodes of progression, and 40 (GOG-218) – 135 (ICON-7) deaths per 1 000 patients. A marked increase in risk of hypertension of Grade ≥3 was observed, with an absolute increase of 59 episodes per 1 000 patients in the ICON-7 study, and 157 episodes in the GOG-218 study, respectively, the majority of which were controlled by means of appropriate treatment. The increased risk of other adverse events considered was negligible. Conclusions: the positive effects produced should be viewed as taking prevalence over the negative effects (FAVOURABLE benefit/harm ratio)

Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer

To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test and correlated them for each patient with time-to-progression (TTP) and overall survival (OS). We obtained values of HER2/chromosome 17 centromere (CEP17) ratio ranging from 2.5 to 21 (median 7.2). At the Cox model there is indication that patients whose tumors have high-level HER2/CEP17 ratio have shorter TTP and OS than those with lower ratio, when treated with a trastuzumab-based regimen. Correlations do not reach the limits of statistical significance but no formal sample size calculation was performed due to the explorative nature of the study. If confirmed in larger cohorts of patients, HER2/CEP17 ratio could represent a reliable and economical predictor of response to trastuzumab-based therapy in MBC

Gender influence on professional satisfaction and gender issue perception among young oncologists. A survey of the Young Oncologists Working Group of the Italian Association of Medical Oncology (AIOM)

Background: The professional gender gap is increasingly recognised in oncology. We explored gender issues perception and gender influence on professional satisfaction/gratification among young Italian oncologists. Methods: Italian oncologists aged 6440 years and members of the Italian Association of Medical Oncology were invited to participate in an online survey addressing workload/burnout, satisfaction in professional abilities and relations, relevant factors for professional gratification, and gender barriers. \u3c72 test for general association or \u3c72 test for trend was used to analyse the data. Results: 201 young oncologists participated in the survey: 67% female, 71% aged 30-40 years, 41% still in training and 82% without children. Women and men were equally poorly satisfied by the relations with people occupying superior hierarchical positions. There was heterogeneity between women and men in current (p=0.011) and expected future (p=0.007) satisfaction in professional abilities: women were more satisfied by current empathy and relations with colleagues and were more confident in their future managerial and team leader skills. The most important elements for professional gratification indicated by all participants were, in general, work-life balance (36%) and intellectual stimulation/research (32%); specifically for women, work-life balance (48%) and intellectual stimulation/research (20%); and specifically for men, career (29%) and social prestige/recognition (26%). Heterogeneity within the same gender emerged. For example, the elements indicated by men as the most important were intellectual stimulation/research (39%) and work-life balance (21%) in general, versus social prestige/recognition (24%) and career (24%), respectively, specifically for men (p<0.0001). More women versus men perceived gender issue as an actual problem (60% vs 38%, p=0.03); men underestimated gender barriers to women's career (p=0.011). Conclusions: Satisfaction in professional abilities varied by gender. Work-life balance is important for both women and men. Stereotypes about gender issues may be present. Gender issue is an actual problem for young oncologists, mostly perceived by women

Visual field loss and vision-related quality of life in the Italian Primary Open Angle Glaucoma Study.

The aim of this study was to examine the relationship between visual field (VF) loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a large cohort of primary open angle glaucoma (POAG) patients. POAG patients with or without VF defects or "glaucoma suspect" patients were considered eligible. QoL was assessed using the validated versions of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis. 13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores than VFD-2 both in Func-4 (p &lt; 0.001) and Symp-6 domains (p = 0.035). Regarding the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated with vision-related QoL deterioration, irrespective of visual acuity

Factors Affecting Mortality in 1022 COVID-19 Patients Referred to an Emergency Department in Bergamo during the Peak of the Pandemic

The unexpected outbreak of COVID-19 in the area of Bergamo and the general crisis of personnel and devices has been managed as well as possible during the maximum peak of epidemic; Humanitas Gavazzeni Hospital implemented its facilities and organization in order to optimize the treatment of patients. The number of beds in the Intensive Care Unit (ICU) was doubled (from 16 to 33), and more than 220 beds were dedicated to the COVID-19 patients. This paper analyzes the factors affecting mortality in 1022 COVID-19 patients who referred to Humanitas Gavazzeni between February 25 and March 26, 2020. A total of 274 (34.9%) fatal events were registered: 202 among those admitted to the Intensive Care Unit (ICU) and COVID department and 72 among those treated in Acute Admission Unit Level II (AAUl-2) who died before hospital admission. This paper studies 274 dead cases by analyzing patient's characteristics, physiological and laboratory parameters, symptoms, and the scores of severity of the disease. Patients who had fatal events in the AAUL-2 showed the worst parameters of risk. The most important differences regarded the Apache II score, Glasgow Coma Score (GCS), CRP (C-reactive protein), pH, creatinine, RR (respiratory rate), and asthenia

Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

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Diagnostic and prognostic values of PBMC proteins in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which there are no validated biomarkers. Previous exploratory studies have identified a panel of candidate protein biomarkers in peripheral blood mononuclear cells (PBMCs) that include peptidyl-prolyl cis-trans isomerase A (PPIA), heat shock cognate protein 71 kDa (HSC70), heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) and TDP-43. It has also been found that PPIA plays a key role in the assembly and dynamics of ribonucleoprotein (RNP) complexes and interacts with TDP-43. Its absence accelerates disease progression in a SOD1 mouse model of ALS, and low levels of PPIA in PBMCs are associated with early-onset ALS. However, the diagnostic and prognostic values of PPIA and the other candidate protein biomarkers have not been established. We analyzed the PBMC proteins in a well-characterized cohort of ALS patients (n=93), healthy individuals (n=104) and disease controls (n=111). We used a highly controlled sample processing procedure that implies two-step differential detergent fractionation. We found that the levels of the selected PBMC proteins in the soluble and insoluble fraction, combined, have a high discriminatory power for distinguishing ALS from controls, with PPIA, hnRNPA2B1 and TDP-43 being the proteins most closely associated with ALS. We also found a shift toward increased protein partitioning in the insoluble fraction in ALS and this correlated with a worse disease phenotype. In particular, low PPIA soluble levels were associated with six months earlier death. In conclusion, PPIA is a disease modifier with prognostic potential. PBMC proteins indicative of alterations in protein and RNA homeostasis are promising biomarkers of ALS, for diagnosis, prognosis and patient stratification

Latanoprost and Dorzolamide for the Treatment of Pediatric Glaucoma: The Glaucoma Italian Pediatric Study (Gipsy), Design and Baseline Characteristics

INTRODUCTION: To investigate the efficacy of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. METHODS: Single arm, prospective, interventional multicenter study. Primary pediatric glaucoma patients younger than 13 years after a single surgical procedure with IOP between 22 and 26 mmHg were considered eligible. At baseline, patients were allocated to latanoprost monotherapy once daily. Depending on intraocular pressure (IOP) reduction at first visit, the patients were allocated to one of three groups: continuation of latanoprost monotherapy, addition of dorzolamide twice daily, or switch to dorzolamide three times daily. The same approach for allocation in medication groups was used in all subsequent visits. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered non-responders and withdrawn. Study treatment and patient follow-up will continue for 3 years or until treatment failure. The primary endpoint is the percentage of responders. Secondary endpoints are time to treatment failure and frequency of adverse events. RESULTS: A total of 37 patients (69 eyes) were enrolled. The mean age was 4.0 ± 3.8 years, the female/male ratio was 1/1.7, and the majority of patients were Caucasian. Eighty percent of patients had bilateral glaucoma. Goniotomy was the most frequently performed surgery (38.6%), followed by trabeculotomy (22.8%), trabeculectomy (21.1%), and trabeculectomy plus trabeculotomy (17.5%). The baseline IOP was 23.6 ± 1.5 mmHg. CONCLUSION: The study population is representative of patients frequently encountered after the first surgery for primary pediatric glaucoma. The study will produce evidence on the medium-term efficacy of a defined pharmacological approach