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.

(+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis. RESULTS: Treatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 µM and 5 µM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers ß-galactosidase, γH2Ax and Klotho-beta. CONCLUSIONS: In conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects.

(+)-Lipoic Acid Reduces Lipotoxicity and Regulates Mitochondrial Homeostasis and Energy Balance in an In Vitro Model of Liver Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipids within hepatocytes, which compromises liver functionality following mitochondrial dysfunction and increased production of reactive oxygen species (ROS). Lipoic acid is one of the prosthetic groups of the pyruvate dehydrogenase complex also known for its ability to confer protection from oxidative damage because of its antioxidant properties. In this study, we aimed to investigate the effects of lipoic acid on lipotoxicity and mitochondrial dynamics in an in vitro model of liver steatosis. HepG2 cells were treated with palmitic acid and oleic acid (1:2) to induce steatosis, without and with 1 and 5 µM lipoic acid. Following treatments, cell proliferation and lipid droplets accumulation were evaluated. Mitochondrial functions were assessed through the evaluation of membrane potential, MitoTracker Red staining, expression of genes of the mitochondrial quality control, and analysis of energy metabolism by HPLC and Seahorse. We showed that lipoic acid treatment restored membrane potential to values comparable to control cells, as well as protected cells from mitochondrial fragmentation following PA:OA treatment. Furthermore, our data showed that lipoic acid was able to determine an increase in the expression of mitochondrial fusion genes and a decrease in mitochondrial fission genes, as well as to restore the bioenergetics of cells after treatment with palmitic acid and oleic acid. In conclusion, our data suggest that lipoic acid reduces lipotoxicity and improves mitochondrial functions in an in vitro model of steatosis, thus providing a potentially valuable pharmacological tool for NAFLD treatment.

Dietary patterns and internalizing symptoms in children and adolescents: A meta-analysis.

CONTEXT: Studies of child and adolescent internalizing symptoms and dietary pattern have produced mixed results. OBJECTIVES: To quantify the association between dietary patterns and internalizing symptoms, including depression, in children and adolescents. DATA SOURCES: Embase, PsycINFO, MEDLINE, Web of Science and Cochrane up to March 2021. STUDY SELECTION: Observational studies and randomized controlled trials with mean age ⩽ 18 years, reporting associations between diet patterns and internalizing symptoms. DATA EXTRACTION: Mean effect sizes and 95% confidence intervals were determined under a random-effects model. RESULTS: Twenty-six studies were cross-sectional, 12 were prospective, and 1 used a case-control design. The total number of participants enrolled ranged from 73,726 to 116,546. Healthy dietary patterns were negatively associated with internalizing (r = -0.07, p < 0.001, 95% confidence interval [-0.12, 0.06]) and depressive symptoms (r = -0.10, p < 0.001, 95% confidence interval [-0.18, -0.08]). Effect sizes were larger for studies of healthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures, as well as in cross-sectional studies of healthy dietary patterns and depression compared to prospective studies. Unhealthy dietary patterns were positively associated with internalizing (r = 0.09, p < 0.001, 95% confidence interval [0.06, 0.14]) and depressive symptoms (r = 0.10, p < 0.01, 95% CI [0.05, 0.17]). Larger effect sizes were observed for studies of unhealthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures. LIMITATIONS: A lack of studies including clinical samples and/or physician diagnosis, and a paucity of studies in which anxiety symptoms were the primary mental health outcome. CONCLUSION: Greater depression and internalizing symptoms are associated with greater unhealthy dietary patterns and with lower healthy dietary intake among children and adolescents.

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.

The Regeneración Urbana, Calidad de Vida y Salud - RUCAS project: a Chilean multi-methods study to evaluate the impact of urban regeneration on resident health and wellbeing.

BACKGROUND: The available evidence of the health effects of urban regeneration is scarce In Latin America, and there are no studies focused on formal housing that longitudinally evaluate the impact of housing and neighborhood interventions on health. The "Regeneración Urbana, Calidad de Vida y Salud" (Urban Regeneration, Quality of Life, and Health) or RUCAS project is a longitudinal, multi-method study that will evaluate the impact of an intervention focused on dwellings, built environment and community on the health and wellbeing of the population in two social housing neighborhoods in Chile. METHODS: RUCAS consists of a longitudinal study where inhabitants exposed and unexposed to the intervention will be compared over time within the study neighborhoods (cohorts), capitalizing on interventions as a natural experiment. Researchers have developed a specific conceptual framework and identified potential causal mechanisms. Proximal and more distal intervention effects will be measured with five instruments, implemented pre- and post-interventions between 2018 and 2021: a household survey, an observation tool to evaluate dwelling conditions, hygrochrons for measuring temperature and humidity inside dwellings, systematic observation of recreational areas, and qualitative interviews. Survey baseline data (956 households, 3130 individuals) is presented to describe sociodemographics, housing and health characteristics of both cohorts, noting that neighborhoods studied show worse conditions than the Chilean population. DISCUSSION: RUCAS' design allows for a comprehensive evaluation of the effects that the intervention could have on various dimensions of health and health determinants. RUCAS will face some challenges, like changes in the intervention process due to adjustments of the master plan, exogenous factors -including COVID-19 pandemic and associated lockdowns- and lost to follow-up. Given the stepped wedge design, that the study capitalizes on within household changes over time, the possibility of adjusting data collection process and complementarity of methods, RUCAS has the flexibility to adapt to these circumstances. Also, RUCAS' outreach and retention strategy has led to high retention rates. RUCAS will provide evidence to inform regeneration processes, highlighting the need to consider potential health effects of regeneration in designing such interventions and, more broadly, health as a key priority in urban and housing policies.

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.

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.

[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.

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.

[Relevance of NANDA-I diagnoses in patients undergoing haematopoietic stem cell transplantation: a Delphi study]. / Rilevanza delle diagnosi NANDA-I nei pazienti sottoposti a Trapianto di Cellule Staminali Emopoietiche: uno studio Delphi.

INTRODUCTION: Haematopoietic Stem Cell Transplantation ( HSCT) has become the standard of care for some haematological diseases that do not respond to traditional treatments: pre-transplant therapy still causes high mortality and morbidity today. Due to the high risk, patient care requires careful evalua- tion and often complex, intensive and non-risk free interventions; the NANDA-I classification provides a way to classify and standardise areas of nursing interest. A previous consensus among experts had iden- tified 61 diagnoses, according to the classification NANDA-I 2018-2020, relevant in onco-haematolo- gical field. OBJECTIVE: The aim of the study was to identify which of the 61 diagnoses were relevant for patients undergoing HSCT. METHOD: A Delphi study was conducted in two rounds; a structured questionnaire on a 4 point Likert scale was used to build consensus, involving 57 experienced nurse enrolled in Italian GITMO Centres. RESULTS: The present study has identified 34 relevant NANDA-I diagnoses in patients undergoing HSCT; it also defined 11 as important diagnoses having obtained absolute consensus. DISCUSSION: Use the NANDA-I diagnoses to know, from a panel of experts, the most important and relevant health problems associated with the toxicity of pre- HCSE treatment, it can direct assistance and resources towards expercied and known outcomes so as to be able to intervene effectively with performances aimed at reducing risks and specific complications.

BMI variation increases recurrence risk in women with early-stage breast cancer.

AIMS: The prognostic role of BMI variation during and/or after treatments for early-stage breast cancer is still unknown. PATIENTS & METHODS: The χ(2) test was conducted to explore the correlation between breast cancer recurrence and BMI changes in 520 early-stage breast cancer patients. Cox proportional hazard models were used to analyze the association of BMI changes, baseline BMI, known prognostic factors and recurrences. RESULTS: BMI gain was significant determinant of recurrences (p = 0.0008). In multivariate analyses, BMI variation more than 5.71% was associated with higher rates of recurrences, as well as age less than 55 years, stage disease and molecular subtype. CONCLUSION: Women who experience BMI gain after breast cancer may be at increased risk of poor outcomes.

Biweekly combination of trastuzumab, docetaxel and gemcitabine for HER2-positive metastatic breast cancer: results of a Phase II GOIM study.

AIMS: Clinical activity of chemotherapy plus trastuzumab in HER2 overexpressing advanced breast cancer has been documented. We report the activity and safety results of biweekly combination of trastuzumab, docetaxel and gemcitabine as first-line therapy in HER2-positive advanced breast cancer. PATIENTS & METHODS: Patients were biweekly treated with trastuzumab (4 mg/kg), gemcitabine (1000 mg/m(2)) and docetaxel (50 mg/m(2)). The primary end point was overall response rate, secondary time to progression, clinical benefit rate (partial response plus complete response plus stable disease for ≥ 24 weeks) and tolerability. RESULTS: A total of 65 patients with HER2-positive advanced breast cancer have been enrolled. In total, 47 patients responded (73%; 95% CI, 60-84), 11 achieved complete response (17%; 95% CI: 8.9-28.7), 36 achieved partial response (56%; 95% CI: 43-68.6). The clinical benefit rate was 87.5% (95% CI: 77-94). Three patients (4.7%) experienced progressive disease. The median time to progression was 14.2 months (95% CI: 10.6-17.8), the median overall survival was 39.3 months and the 36-month survival rate was 55.5% (95% CI: 58-73). The worst toxicities were grade 3 neutropenia (12%), thrombocytopenia (6%) and diarrhea (6%). No cardiac toxicity was reported. CONCLUSION: As first-line therapy, this combination allowed the delivery of polychemotherapy in association to targeted therapy, with clinical activity and mild toxicity. The promising results should be further explored in Phase III randomized clinical trials.

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.

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.

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.