Comparative evaluation of cigarette smoke and a heated tobacco product on microglial toxicity, oxidative stress and inflammatory response.

BACKGROUND: Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. METHODS: We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. RESULTS: Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho ß. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. CONCLUSION: These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit.

Fish Oil Containing Pro-Resolving Mediators Enhances the Antioxidant System and Ameliorates LPS-Induced Inflammation in Human Bronchial Epithelial Cells.

Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. This study investigates the cellular mechanisms of fish oil in an in vitro model of lung inflammation using lipopolysaccharide (LPS) on a healthy human bronchial epithelium cell line. LPS exposure for 24 h reduced cell viability, elevated reactive oxygen species (ROS), depleted glutathione (GSH), and induced mitochondrial depolarization, indicating oxidative stress and inflammation. Fish oil administration significantly mitigated ROS production, prevented GSH depletion, and reduced mitochondrial depolarization. This was associated with the upregulation of the endogenous antioxidant system, evidenced by restored GSH levels and the increased gene expression of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). Fish oil also suppressed IL-6 and IL-1ß expression and increased anti-inflammatory cytokine IL-10 expression. Furthermore, fish oil upregulated the expression of pro-resolving mediator receptors, suggesting a role in inflammation resolution. These findings highlight the potential of fish oil supplementation as a preventive measure against pulmonary diseases characterized by unresolved inflammation such as lung inflammation.

Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial.

BACKGROUND: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. METHODS: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A). CONCLUSIONS: First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.

Nursing Management in Pediatric Patients Undergoing Chimeric Antigen Receptor T (CAR-T) Cell Therapy: A Systematic Literature Review.

OBJECTIVES: This systematic review aims to describe an overview of the overall care, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing chimeric antigen receptor T (CAR-T) cell infusion in order to provide an updated summary of the approach to the management of these patients. CAR-T cellular therapy represents an innovation within pediatric hematology and oncology used to treat relapse and refractory leukemias, solid tumors, and lymphomas when standard therapy has not worked. However, this type of therapy could lead to the onset of some clinical complications that must be managed appropriately and promptly. Although their use is constantly increasing, the knowledge and resources in the literature are still limited. DATA SOURCES: The review was conducted from January 2022 to July 2022 in PubMed, CINAHL, Scopus, and Cochrane and produced 502 articles. Based on the selection criteria and after removing duplicate articles, 26 articles were included in the study. CONCLUSION: From these analyzed articles, it was possible to have an overview regarding the management, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing CAR-T cell infusion. IMPLICATIONS FOR NURSING PRACTICE: The management of hematology-oncology patients undergoing CAR-T cell therapy from a nursing perspective is not simple. We hope this review can be used as a tool to guide nursing staff. In this regard, we have developed a summary table with the actions to be taken in the case of assisting a pediatric patient being treated with CAR-T.

Predictive factors of sleep quality and burnout in nurses working in transplant units during the COVID-19 lockdown - A cross-sectional study.

Background: There is minimal information regarding sleep disturbance and burnout during COVID-19 in nurses working within haematology-oncology and hematopoietic stem cell transplantation (HSCT) settings.Aim: To identify socio-demographic and professional factors that predicted burnout and sleep disturbance during COVID-19 in nurses working in HSCT settings.Design/Methods: Data were collected using the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index. Descriptive statistics and linear regression examined relationships.Results: 308 responses were received. Nurses working in outpatient settings had greater emotional exhaustion (Rpartial = -0.12, n = 308, p = 0.03). Negative predictors for quality of sleep were transplant programme setting (Rpartial = -0.19, n = 308, p < 0.01) and years working in HSCT (Rpartial = -0.17, n = 308, p < 0.01). Other relationships were found on univariate analysis.Conclusion: Institutions must offer programmes for nurses to develop sleep strategies, self-care, and work-related stress management.

Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: Final Results From the Phase 2 METEORA-II Randomized Clinical Trial.

Importance: In spite of the effectiveness of endocrine therapy plus cyclin-dependent kinase (CDK) 4/6 inhibitors as the first-line treatment for estrogen receptor (ER)-positive, erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2/neu])-negative (ER+/ERBB2-) metastatic breast cancer (MBC), patients eventually develop resistance, and eventually most will receive chemotherapy. The METEORA-II trial compared a metronomic all-oral treatment with intravenous (IV) chemotherapy. Objective: To compare the efficacy of the oral vinorelbine plus cyclophosphamide plus capecitabine (VEX) regimen vs weekly IV paclitaxel among patients with ER+/ERBB2- MBC who are candidates for chemotherapy. Design, Setting, and Participants: This phase 2 randomized clinical trial including 140 women 18 years and older (randomized 1:1) with ER+/ERBB2- MBC was carried out from September 13, 2017, to January 14, 2021 at 15 centers in Italy. Eligible patients could have received 1 prior line of chemotherapy for MBC and/or 2 lines of endocrine therapy (including CDK4/6 inhibitors). Interventions: In 4-week cycles, patients received either metronomic oral VEX or weekly IV paclitaxel. Main Outcomes and Measures: The primary end point was investigator-assessed time to treatment failure (TTF) defined as the interval between the date of randomization to the end of treatment (because of disease progression or lack of tolerability or because further trial treatment was declined). Secondary end points included progression-free survival (PFS), overall survival (OS), and disease control rate (complete or partial response or stable disease lasting for at least 24 weeks). Results: In total, 133 patients received either VEX (n = 70) or paclitaxel (n = 63) in 4-weekly cycles. The median age was 61 (range, 30-80) years. The VEX treatment significantly prolonged TTF vs paclitaxel (hazard ratio [HR], 0.61; 95% CI, 0.42-0.88; P = .008), median TTF was 8.3 (95% CI, 5.6-11.1) months for VEX vs 5.7 (95% CI, 4.1-6.1) months for paclitaxel, and the 12-month TTF was 34.3% for VEX vs 8.6% for paclitaxel. The median PFS was 11.1 (95% CI, 8.3-13.8) months vs 6.9 (95% CI, 5.4-10.1) months favoring VEX (HR, 0.67; 95% CI, 0.46-0.96, P = .03). The 12-month PFS was 43.5% for VEX vs 21.9% for paclitaxel. No difference in OS was found. The TF event for 55.6% of patients was progression of disease; for 23% it was AEs. More patients assigned to VEX had at least 1 grade 3 or 4 targeted adverse event (VEX, 42.9%; 95% CI, 31.1%-55.3% vs paclitaxel, 28.6%; 95% CI, 17.9%-41.3%), but essentially no alopecia. Conclusion and Relevance: This randomized clinical trial found significantly prolonged TTF and PFS for oral VEX but no improvement in OS compared with intravenous paclitaxel, despite increased but still manageable toxic effects. The VEX regimen may provide more prolonged disease control than weekly paclitaxel for ER+/ERBB2- MBC. Trial Registration: ClinicalTrials.gov Identifier: NCT02954055.

IGFBP-6 Alters Mesenchymal Stromal Cell Phenotype Driving Dasatinib Resistance in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML), BCR-ABL1-positive, is classified as a myeloproliferative characterized by Philadelphia chromosome/translocation t(9;22) and proliferating granulocytes. Despite the clinical success of tyrosine kinase inhibitors (TKi) agents in the treatment of CML, most patients have minimal residual disease contained in the bone marrow microenvironment, within which stromal cells assume a pro-inflammatory phenotype that determines their transformation in cancer-associated fibroblasts (CAF) which, in turn can play a fundamental role in resistance to therapy. Insulin-like Growth Factor Binding Protein-6 (IGFBP-6) is expressed during tumor development, and is involved in immune-escape and inflammation as well, providing a potential additional target for CML therapy. Here, we aimed at investigating the role of IGFBP-6/SHH/TLR4 axis in TKi response. We used a CML cell line, LAMA84-s, and healthy bone marrow stromal cells, HS-5, in mono- or co-culture. The two cell lines were treated with Dasatinib and/or IGFBP-6, and the expression of inflammatory markers was tested by qRT-PCR; furthermore, expression of IGFBP-6, TLR4 and Gli1 were evaluated by Western blot analysis and immumocytochemistry. The results showed that both co-culture and Dasatinib exposure induce inflammation in stromal and cancer cells so that they modulate the expression of TLR4, and these effects were more marked following IGFBP-6 pre-treatment suggesting that this molecule may confer resistance through the inflammatory processes. This phenomenon was coupled with sonic hedgehog (SHH) signaling. Indeed, our data also demonstrate that HS-5 treatment with PMO (an inducer of SHH) induces significant modulation of TLR4 and overexpression of IGFPB-6 suggesting that the two pathways are interconnected with each other and with the TLR-4 pathway. Finally, we demonstrated that pretreatment with IGFBP-6 and/or PMO restored LAMA-84 cell viability after treatment with Dasatinib, suggesting that both IGFBP-6 and SHH are involved in the resistance mechanisms induced by the modulation of TLR-4, thus indicating that the two pathways may be considered as potential therapeutic targets.

How to manage falls in hospitalized patients: A single center experience in allogeneic stem cell transplantation setting.

ABSTRACT: In allogeneic hematopoietic stem cell transplantation (AHSCT), falls can lead to immediate and late consequences and in some cases to death. We analyzed risks and causes of falls with root cause analysis (RCA) based on which improvement interventions were implemented.A retrospective observational study was conducted to analyze with RCA data of incidence reports and medical records of patients admitted; an expert panel identified actions to prevent falls, which were collected in a checklist.Between December 2017 and November 2019, 214 patients were admitted to ordinary hospital stays for AHSCT or AHSCTrelated complications. In this period, 15 falls, involving 11 patients, occurred resulting in a 2.32 d/patient incidence. In 66.67% of cases minor head trauma occurred. Diuretic drugs (93.33%), induced hyper-diuresis in nonbladder catheter patients (93.33%) and antihypertensive drugs (93.33%) were reported as most common cause in our incident reports. The most frequent fall time slot was between 10 PM and 7 AM (60%). We determined with RCA diuretics and consequent induced hyper-diuresis (80%), self-insufficiency (40%), antihypertensive (33.3%) and noncompliance (33.3%) as the most common cause of falls. Finally, 16 actions, collected in a "safe comfort" checklist, were identified to prevent falls.Diuretic drugs inducing hyper-diuresis, self-insufficiency, poor patient compliance, orthostatic hypotension, fever, night-time and obstacles within inpatient units are the most common contributing factors. Therefore, administration of diuretic and antihypertensive drugs should be rescheduled and a multidimensional risk assessment scale integrated with a preventive action plan, such as the safe comfort checklist, should be implemented to reduce falls.

The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress.

Breast cancer is the most frequent tumor and the leading cause of cancer deaths in women. In recent years, lactate metabolism and, in particular, its receptor GPR81 have been shown to play a vital role in cancer biology. GPR81 is upregulated in breast cancer and promotes tumor growth by tumor cell-derived lactate. Therefore, the search for possible crosstalk and the involvement of new molecules capable of generating this pathology is always in continuous development. In this study, the relationship between GPR81 and IGFBP6 protein in tumor growth and oxidative stress in the human breast cancer cell line MDA-MB-231 was studied. Cells were treated with lactate or the GPR81 receptor agonist and antagonist 3,5-DHBA and 3-OBA, respectively. In addition, oxidative stress and proliferation were also evaluated in cells challenged with the recombinant IGFBP6 protein. Our data showed that lactate induced cell proliferation and wound healing of the MDA-231 breast cancer cell through the overexpression of both the lactate receptor GPR81 and IGFBP6. The increase in IGFBP6 was able, in turn, to improve the mitochondrial fitness and redox state, as suggested by the reduced levels of mitochondrial ROS production after IGFBP6 treatment, presumably mediated by the increase in the ROS detoxifying genes HMOX1, GSTK1 and NQO1. In conclusion, our data highlight a novel axis between GPR81 and IGFBP6 in MDA-231 cells able to modulate lactate metabolism and oxidative stress. This complex signaling may represent a new therapeutic target for breast cancer.

Nurses' Physical and Psychological Symptoms During the first COVID-19 Lockdown in Italy: a Nationwide Cross-Sectional Study in Stem Cell Transplantation Setting.

BACKGROUND AND OBJECTIVE: Northern Italy was one of the first European territories to deal with the Coronavirus Disease 2019 (COVID-19) outbreak. Drastic emergency restrictions were introduced to contain the spread and limit pressure on healthcare facilities. However, nurses were at high risk of developing physical, mental, and working issues due to professional exposure. The aim of this cross-sectional study was to investigate these issues among nurses working in Italian hematopoietic stem cell transplant (HSCT) centers during the COVID-19 pandemic. METHODS: Data were collected online immediately after the first "lockdown" period in order to investigate the prevalence of physical issues, sleep disorders, and burnout symptoms and explore correlations with COVID-19 territorial incidence in Northern Italian regions versus Central and Southern Italian regions. RESULTS: Three hundred and eight nurses working in 61 Italian HSCT Units responded to the survey. Depression, cough, and fever were more frequently reported by nurses working in geographical areas less affected by the pandemic (p=0.0013, p<0.0001, and p=0.0005 respectively) as well as worst sleep quality (p=0.008). Moderate levels of emotional exhaustion (mean±SD -17.4±13.0), depersonalization (5.3±6.1), and personal accomplishment (33.2±10.7) were reported without significant differences between territories. CONCLUSIONS: different COVID-19 incidence among territories did not influence nurses' burden of symptoms in the HSCT setting. However, burnout and insomnia levels should be considered by health care facilities in order to improve preventive strategies.

Lactate Rewrites the Metabolic Reprogramming of Uveal Melanoma Cells and Induces Quiescence Phenotype.

Uveal melanoma (UM), the most common primary intraocular cancer in adults, is among the tumors with poorer prognosis. Recently, the role of the oncometabolite lactate has become attractive due to its role as hydroxycarboxylic acid receptor 1 (HCAR1) activator, as an epigenetic modulator inducing lysine residues lactylation and, of course, as a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. The aim of the present study was to dissect in UM cell line (92.1) the role of lactate as either a metabolite or a signaling molecule, using the known modulators of HCAR1 and of lactate transporters. Our results show that lactate (20 mM) resulted in a significant decrease in cell proliferation and migration, acting and switching cell metabolism toward oxidative phosphorylation. These results were coupled with increased euchromatin content and quiescence in UM cells. We further showed, in a clinical setting, that an increase in lactate transporters MCT4 and HCAR1 is associated with a spindle-shape histological type in UM. In conclusion, our results suggest that lactate metabolism may serve as a prognostic marker of UM progression and may be exploited as a potential therapeutic target.

Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial.

BACKGROUND: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2- metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. METHODS: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). RESULTS: In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1-13.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7-10.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47-1.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0-47.8) in the combination arm versus 33.5 (95% CI 26.4-42.7) in the AI alone arm (HR 1.0, 95% CI 0.61-1.62). CONCLUSIONS: EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard. TRIAL REGISTRATION: EudraCT: 2013-004153-24.

Management of Pain and Anxiety during Bone Marrow Aspiration: An Italian National Survey.

BACKGROUND: Bone marrow aspiration (BMA) or biopsy is a necessary and frequent procedure for diagnosis and monitoring of hematological diseases. Pharmacological pain management approaches exist; however, previous experience and psychological preparation for BMA may impact pain perception. AIMS: This study aimed to explore current practices in procedural pain management for BMA or biopsy. DESIGN/SETTING/PARTICIPANTS: A cross-sectional internet-based survey was performed by the Nurses Group of the Italian Transplant Group (GITMO). Participants were nurses working in bone marrow transplant centers regularly performing BMA/biopsies. RESULTS: Sixty out of 94 centers receiving the survey responded (63.8%), 47 adult and 13 pediatric centers. The majority of them (75%) provided only verbal information for patient preparation before BMA. . Injected local anesthetics were used in 55.4% of centers, and combined with topical anesthetics in 33.9% of centers. Use of oral anesthetics was rare; however, anxiolytics and benzodiazepines were occasionally used (18.3%, 18.3% respectively). All pediatric centers used deep sedation for the procedure (p < .001), but drug choice depended on anesthetist preference. Ice packs (35.0%) and oral analgesia as required (40.0%) were used for postprocedural pain. Nurses perceived their patients' pain scores as relatively low (3.5 on scale 0-10), but recognized that it was a painful procedure provoking anxiety, and that pain management could be improved. CONCLUSIONS: Results revealed the lack of a standardized approach to procedural pain management for BMA in this study sample. Assessing a patient's pain experience is a key component to identifying effective pain management for BMA.

EFFECT: a randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer.

BACKGROUND: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. METHODS: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). CONCLUSION: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. TRIAL REGISTRATION: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.

Metronomic oral chemotherapy with cyclophosphamide plus capecitabine combined with trastuzumab (HEX) as first line therapy of HER-2 positive advanced breast cancer: A phase II trial of the Gruppo Oncologico Italia Meridionale (GOIM).

BACKGROUND: The combination of chemotherapy plus anti HER-2 agents is the mainstay of HER-2 positive advanced breast cancer (ABC) therapy. We conducted a phase II trial testing activity and safety of trastuzumab and metronomic capecitabine/cyclophosphamide (HEX) as first-line therapy in HER-2 positive ABC.Methods. Patients at first relapse or with synchronous metastasis were treated with trastuzumab (4 mg/kg, biweekly) plus oral capecitabine (1500 mg/daily) and cyclophosphamide (50 mg/daily). Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival (PFS), clinical benefit rate (CBR; PR + CR + SD for ≥ 24 weeks) and tolerability. Optimal two-stage design was applied. RESULTS: Sixty patients with measurable ABC, tumors scored as +3 for HER-2 or FISH +, untreated for advanced disease were enrolled. Median age was 62.5 years, visceral metastases were present in most patients (57.9%). Median number of cycles was 16 (range 1-98). ORR was 56.7% (95% CI, 44.1-68.4%), with 5 CR (8.3%) and 29 PR (48.3%). Fifteen patients had SD (25%). The CBR was 78.2%. Nine progressions were observed (15%). Median PFS was 11 months. One year PFS was 47.7%. Median OS was 45.9 months. Worst toxicities were grade 3 hand-foot syndrome in 2 pts (3.3%), grade 3 anaemia in 2 pts (3.3%), grade 2 nausea in 2 pts (3.3%) and grade 3-4 diarrhea in 2 pts (3.3%). Cardiac toxicity grade 1 was reported in 1 pt. CONCLUSIONS: Combination of trastuzumab and metronomic oral chemotherapy has clinical activity. The tolerability was excellent and allowed the prolonged delivery of treatment.

[Relevance of NANDA-I Diagnosis in Hematopoietic stem cell transplantation patients]. / Rilevanza delle diagnosi NANDA-I nei pazienti sottoposti a Trapianto di Cellule Staminali Emopoietiche (TCSE).

INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) has become the standard of care for many haematological diseases unresponsive to traditional treatments; pretransplant therapy still causes high mortality and morbidity today. Due to the high risk, patient care requires careful assessment and often complex, intensive and non-risk free interventions; the NANDA-I classification provides a way to classify and standardise areas of nursing interest. In 2011, Speksnijder, using the Delphi technique, identified 68 diagnoses relevant to identify health problems in the field of oncohaematology. AIM: Based on Speksnijder's contribution, the study tries to identify which of these diagnoses were relevant in identifying health problems in HSCT patients. METHOD: A quantitative-descriptive study was carried out; a structured questionnaire on a 4-point Likert scale was used to build consensus, involving 57 expert nurses enrolled in the Italian GITMO Centres. RESULTS: Of the 68 NANDA-I diagnoses defined as relevant by Speksnijder in the oncohaematological field, this study identified 37 as relevant in detecting health problems in patients undergoing HSCT (34 in Round 1, 3 in Round 2) and also defined 12 as important diagnoses having obtained an absolute consensus. DISCUSSION: Using the NANDA-I diagnoses to identify, from a panel of experts, the most important and relevant health problems associated with the toxicity of pre-TCSE treatment, allows to focus attention on expected and known outcomes in order to be able to intervene with performances aimed at reducing specific risks and complications.

Nursing role in the assessment and care of hepatic sinusoidal obstruction syndrome patients: a consensus paper by the "Gruppo Italiano Trapianto di Midollo Osseo".

PURPOSE: Sinusoidal obstruction syndrome (SOS) is one of the most serious complications post haematopoietic stem cell transplantation (HSCT). The diagnosis of SOS is clinical, but nurses should be involved in the pre-transplant risk assessment period and play a crucial role in the early detection of signs and symptoms during and after hospitalization. The aim of this work is to achieve a consensus on nurses' behaviour in caring for SOS. METHODS: On behalf of the Italian Group for Bone and Marrow Transplantation (GITMO), a promoter committee was established to put in place a consensus conference approach. A multidisciplinary group of GITMO together with four nurses, three haematology physicians and one patient representative acted as jury, who reviewed the reports and wrote recommendations and suggestions. Recommendations gaining 100% of consensus were considered 'Golden Points of Care'; if a consensus was achieved by ≥ 75% of the jury's members, those recommendations were defined as 'Good Practices'. RESULTS: Eighteen papers written by nurses as first authors have been identified. Golden Points of Care and Good Practices were worked out for the following topics: nurses' role in general, nurses' role in pre-transplant assessment, pre-transplant risk assessment and risk stratification, baseline monitoring, suspected mild or moderate SOS, suspected severe or very severe SOS and late-onset cases. CONCLUSION: SOS is relatively rare; therefore, a holistic approach to the patients' needs considering nursing role as essential may result in better care outcomes.

Eribulin plus trastuzumab in pretreated HER2-positive advanced breast cancer patients: safety and efficacy. An Italian experience.

BACKGROUND: Chemotherapy plus targeted therapy is the established treatment for human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer (BC). Limited data regarding the safety and activity of the combination of eribulin and trastuzumab (E/T) in pretreated HER2-positive advanced BC (ABC) are available. The aim of this observational, retrospective, multicenter study was to examine the tolerability and the clinical activity of E/T in this setting. METHODS: Patients treated with eribulin mesylate plus standard dose of trastuzumab were included. Data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were reported. RESULTS: Between October 2012 and November 2015, 24 consecutive patients with HER2-positive ABC were included. All patients were heavily pretreated: the median number of prior chemotherapy regimens for ABC was 3 (range 2-9). The median number of cycles with E/T was 11.5 (range 2-26). The ORR was 41.7%. Median PFS was 5.4 months, median postprogression survival was 5.4 months, and median OS was 8 months. Neutropenia was the most common grade 3/4 clinical adverse event (16.7%). CONCLUSIONS: Tolerability and clinical activity of the E/T combination schedule are encouraging. The results of this study indicate that this combination might be considered for treatment of pretreated HER2 ABC.

Final results of a prospective study of scalp cooling in preventing chemotherapy-induced alopecia.

Aim: Alopecia is a distressing effect of cancer treatments. Our study examined efficacy and safety of scalp cooling to prevent chemotherapy-induced alopecia. Materials & methods: Early breast cancer patients candidate to anthracycline and/or taxane were eligible. Dean's alopecia scale was used to classify alopecia. Results: From February 2016 to November 2018, 127 women were enrolled; 55 (43.3%) received epirubicin/cyclophosphamide (4 EC 3 weeks) followed by paclitaxel (12 P weeks); 50 (39.4%) received 4 EC 3 weeks; 20 (15.7%) received 12 P weeks/trastuzumab and 2 docetaxel/cyclophosphamide (4 TC 3 weeks). The success rate was 71.7% (G0 21.3%, G1 31.5%, G2 18.9%). Frequent side effects were: coldness, headache, scalp pain and head heaviness. Conclusion: In our study, scalp cooling can prevent alopecia thus supporting the wider use in early breast cancer.