Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile. Patients and methods: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with ≥2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography. Results: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) <0.1 times 109/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 × 109l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotox-icity. Antitumour activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30$), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months. Conclusions: The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimen

Effects of Direct-Acting Antiviral Agents on the Mental Health of Patients with Chronic Hepatitis C: A Prospective Observational Study

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited e cacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant di erence emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side e ects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life

Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study

Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62–10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19

Recommendations for neonatologists and pediatricians working in first level birthing centers on the first communication of genetic disease and malformation syndrome diagnosis: consensus issued by 6 Italian scientific societies and 4 parents’ associations

Background: Genetic diseases are chronic conditions with relevant impact on the lives of patients and their families. In USA and Europe it is estimated a prevalence of 60 million affected subjects, 75% of whom are in developmental age. A significant number of newborns are admitted in the Neonatal Intensive Care Units (NICU) for reasons different from prematurity, although the prevalence of those with genetic diseases is unknown. It is, then, common for the neonatologist to start a diagnostic process on suspicion of a genetic disease or malformation syndrome, or to make and communicate these diagnoses. Many surveys showed that the degree of parental satisfaction with the methods of communication of diagnosis is low. Poor communication may have short and long-term negative effects on health and psychological and social development of the child and his family. We draw up recommendations on this issue, shared by 6 Italian Scientific Societies and 4 Parents’ Associations, aimed at making the neonatologist’s task easier at the difficult time of communication to parents of a genetic disease/malformation syndrome diagnosis for their child. Methods: We used the method of the consensus paper. A multidisciplinary panel of experts was first established, based on the clinical and scientific sharing of the thematic area of present recommendations. They were suggested by the Boards of the six Scientific Societies that joined the initiative: Italian Societies of Pediatrics, Neonatology, Human Genetics, Perinatal Medicine, Obstetric and Gynecological Ultrasound and Biophysical Methodologies, and Pediatric Genetic Diseases and Congenital Disabilities. To obtain a deeper and global vision of the communication process, and to reach a better clinical management of patients and their families, representatives of four Parents’ Associations were also recruited: Italian Association of Down People, Cornelia de Lange National Volunteer Association, Italian Federation of Rare Diseases, and Williams Syndrome People Association. They worked from September 2019 to November 2020 to achieve a consensus on the recommendations for the communication of a new diagnosis of genetic disease. Results: The consensus of experts drafted a final document defining the recommendations, for the neonatologist and/or the pediatrician working in a fist level birthing center, on the first communication of genetic disease or malformation syndrome diagnosis. Although there is no universal communication technique to make the informative process effective, we tried to identify a few relevant strategic principles that the neonatologist/pediatrician may use in the relationship with the family. We also summarized basic principles and significant aspects relating to the modalities of interaction with families in a table, in order to create an easy tool for the neonatologist to be applied in the daily care practice. We finally obtained an intersociety document, now published on the websites of the Scientific Societies involved. Conclusions: The neonatologist/pediatrician is often the first to observe complex syndromic pictures, not always identified before birth, although today more frequently prenatally diagnosed. It is necessary for him to know the aspects of genetic diseases related to communication and bioethics, as well as the biological and clinical ones, which together outline the cornerstones of the multidisciplinary care of these patients. This consensus provide practical recommendations on how to make the first communication of a genetic disease /malformation syndrome diagnosis. The proposed goal is to make easier the informative process, and to implement the best practices in the relationship with the family. A better doctor-patient/family interaction may improve health outcomes of the child and his family, as well as reduce legal disputes with parents and the phenomenon of defensive medicine

Pre-operative radiochemotherapy with raltitrexed for resectable locally-advanced rectal cancer : a phase II study

Background: The aim of the study was to evaluate the response to and toxicity of pre-operative radiochemotherapy containing raltitrexed (Tomudex) for resectable rectal adenocarcinoma. Patients and Methods: From November 2000 to June 2002, 18 consecutive patients staged T3 N0/N+ were treated with pre-operative chemotherapy (3 mg/m 2 of raltitrexed on days 1, 19, 38) and concurrent radiotherapy (RT) (50.4 Gy) in 6 weeks, followed by radical surgery within 8 weeks. Results: The treatment compliance was high. No major acute toxicity was reported. Concerning late toxicity, genitourinary adverse effects were prevalent. A complete response was observed in one patient (6%), partial response in eight (47%), stable disease in seven (41%) and progression in one case. Three-year actuarial disease-free and overall survival rates were 37% and 87.5%, respectively. Conclusion: Raltitrexed did not increase the pathological response rate compared with the rates obtained with use of preoperative RT alone and reported in the literature. Acute morbidity was low and acceptable, while late toxicity was considerable, prevalently concerning sexual dysfunction and urinary complications

Fertility and digital technology: narratives of using smartphone app ‘Natural Cycles’ while trying to conceive

Fertility awareness apps, which help to identify the 'fertile window' when conception is most likely, have been hailed as 'revolutionising' women's reproductive health. Despite rapidly growing popularity, little research has explored how people use these apps when trying to conceive and what these apps mean to them. We draw on in-depth, qualitative interviews, adopting a critical digital health studies lens (a sub-field of science and technology studies), to explore the experiences of cisgender women and partners with one such app, Natural Cycles, in the context of their daily lives. We found that many women valued the technology as a 'natural', inobtrusive alternative to biomedical intervention, and a means of controlling and knowing their bodies, amid a dearth of fertility-related education and care. Yet this technology also intervened materially and affectively into the spaces of their lives and relationships and privileged disembodied metrics (temperature) over embodied knowledge. Meanwhile, app language, advertising and cost have contributed to characterising 'typical' users as white, heterosexual, affluent, cisgender women without disabilities. In the context of neoliberal shifts towards bodily self-tracking, technologies appealing as novel, liberating and 'natural' to individuals who can access them may nevertheless reproduce highly gendered reproductive responsibilities, anxieties and broader health and social inequalities

prognostic value of neutrophil lymphocite ratio in resected high risk colorectal cancer an analysis of adjuvant tosca trial

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p 291the distinctive study a biologically enriched phase ii study of second line folfiri aflibercept in prospectively stratified anti egfr resistant metastatic colorectal cancer patients with ras validated wild type status trial in progress

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From central to sentral (Serum angiogenesis central): Circulating predictive biomarkers to anti-VEGFR therapy

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels’ early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy

thromboembolic risk and survival with khorana score in resected colorectal cancer patients subgroup analysis from the adjuvant tosca trial

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