How many cyberbullying(s)? A non-unitary perspective for offensive online behaviours.

Research has usually considered cyberbullying as a unitary phenomenon. Thus, it has been neglected to explore whether the specific online aggressive behaviours relate differentially to demographic features of the perpetrators of online aggressive actions, their personality characteristics, or to the ways in which they interact with the Internet. To bridge this gap, a study was conducted through a questionnaire administered online to 1228 Italian high-school students (Female: 61.1%; 14-15 yo: 48.%; 16-17 yo: 29.1%; 18-20 yo: 20.4%, 21-25 yo: 1.6%; Northern Italy: 4.1%; Central Italy: 59.2%; Southern Italy: 36.4%). The questionnaire, in addition to items about the use of social media, mechanisms of Moral Disengagement and personality characteristics of the participants in the study, also included a scale for the measurement of cyberbullying through the reference to six aggressive behaviours. The results indicate that cyberbullying can be considered as a non-unitary phenomenon in which the different aggressive behaviours can be related to different individual characteristics such as gender, personality traits and the different ways of interacting with social media. Moreover, the existence of two components of cyberbullying has been highlighted, one related to virtual offensive actions directly aimed at a victim, the other to indirect actions, more likely conducted involving bystanders. These findings open important perspectives for understanding, preventing, and mitigating cyberbullying among adolescents.

Clinical Implications of Multi-Drug Resistant Organisms' Gastrointestinal Colonization in an Internal Medicine Ward: The Pandora's Box.

Background: Multi-drug resistant organisms (MDRO) are an emerging health problem with an important impact on clinical outcome in Intensive Care Units (ICUs) and immunocompromised patients. Conversely, the role of MDRO colonization in Internal Medicine is less clear. The objective of our study is to evaluate the clinical impact (namely sepsis development, in-hospital and 30-days mortality, and re-hospitalization) of MDRO colonization in Internal Medicine. Methods: Patients admitted to our Internal Medicine Unit between January 2019 and March 2020 were potentially includible. Outcomes in patients with a positive rectal swab for MDRO (RS+) and in patients without a RS+ were compared. Results of the multivariate analyses were expressed as Odds Ratios (ORs) and the corresponding 95% Confidence Interval (CI). Results: In a cohort of 2147 patients, 77 patients with RS+ were consecutively identified; 377 patients with a rectal swab negative for MDRO were randomly selected from the same cohort (five for each patient with RS+). At the multivariate analysis, RS+ was associated with an increased risk of sepsis development during hospitalization (OR 4.18; 95% CI, 1.99-8.78) and with death or re-hospitalization at 30 days (OR 4.79; 95% CI, 2.79-8.23), whereas RS+ did not appear to be associated with death during hospitalization or need for ICU transfer. Conclusions: Our results suggest for the first time a prognostic role for RS+ in Internal Medicine. Thus, assessment of rectal swab at hospital admission appears useful even in this setting. However, larger prospective studies and a cost-benefit analysis are needed to confirm our preliminary findings.

Hospitalization and mortality for acute exacerbation of asthma: an Italian population-based study.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma.

University Teachers During the First Lockdown Due to SARS-CoV-2 in Italy: Stress, Issues and Perceptions of Misconduct.

With the spread of the pandemic and the introduction of measures aimed at its containment, it is necessary to understand in specific national contexts how home quarantine has affected the psychophysical well-being of academics, and their ability to maintain integrity. To this end we constructed an online questionnaire to investigate the levels of stress, well-being, and work-life balance in relationship with living and working conditions. Moreover, the questionnaire was designed to obtain information about the perceived occurrence, increase or decrease of misconduct in research (e.g., research misconduct by colleagues) and professional relationships (e.g., misbehaviors between colleagues, from students and toward students). The questionnaire was administered online by contacting faculty at three universities in Tuscany, Italy, asking them to relate their experience during the first lockdown (March-May 2020). Faculty members were invited to complete the questionnaire by their institutional e-mail account. The final sample consisted of 581 respondents. The results showed that inadequacies of the equipment, and particularly poor internet connection, were significantly correlated with main issues reported, such as relationships with students and research activities. Female teachers primarily suffered from stressful conditions, lacked well-being, and experienced work-life imbalance. Stress levels were related to perceptions of the frequency of misconduct and of an increase in their frequency during the period of home quarantine. Female professors, when compared to their male counterparts, perceived misconduct from students as increased and more frequent in the period of quarantine. Results point to a gender issue that is likely to arise from conditions of domestic activities imbalance and that increases stress and misconduct perception.

Mid-air haptics for shape recognition of virtual objects.

This paper presents an experiment in which participants had to discriminate three mid-air haptic shapes (circle, square, point) by reporting whether the haptic stimulus (e.g. circle on the palm of the hand) was compatible with an image (e.g. a circle) or a word (e.g. 'circle') displayed on a screen. Results indicate that only the 'point' stimulus was appreciably recognised and discriminated in terms of accuracy and time needed for the identification. Accuracy increased with repetition, and response time decreased, suggesting a learning effect. The comparison between visual and textual labels shows that for the haptic point stimulus there is no significant difference but a tendency to have greater accuracy with images than with texts, while the opposite result is found for the circle stimulus. This outcome suggests the need for new experiments focussed of the effect of visual/textual labels to make the recognition/discrimination tasks of haptic stimuli easier. Practitioner Summary: Three haptic shapes were presented with images or texts, matching or not the stimuli. The point was easy to recognise, while the circle and the square were difficult to discriminate against each other. Visual/textual labels bring contradictory results for different shapes. Abbreviations: 1D: one-dimensional; 2D: two-dimensional; 3D: three-dimensional; API: application programming interface; cm: centimeter; GLMM: generalised linear mixed-effect model; HCI: human-computer interaction; Hz: hertz; LMM: linear mixed-effect model; MCC: Matthews' correlation coefficient; mm: millimeter; ms: millisecond; QQ-plot: Quantile-Quantile plot; SD: standard deviation.

Ferritin as prognostic marker in COVID-19: the FerVid study.

BACKGROUND: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients. METHODS: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit. RESULTS: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count. CONCLUSION: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.

Flight flexibility in strategic traffic planning: visualisation and mitigation use case.

The concept of strategic traffic planning that takes into account changing airspace configurations, their capacity, and allows the quantification of flight flexibility is presented in this paper: the visualization of the results and an example of possible use. The concept is implemented through two deterministic optimization models. Here, we focus on the output of the models, which identifies the departure times, trajectories, flight flexibility and the list of saturated sector-hours throughout the day, based on the configurations used during the day. In order to make the output understandable to various stakeholders, we use a visualization tool and a set of performance indicators. The information on the saturated sectors, and their impact on flexibility (criticality index) is taken as an input in the example of mitigation action application by Air Navigation Service Providers, aimed at improving the situation. A mitigation strategy of increasing capacity of saturated airspace is implemented, and results show that the improvements in flexibility can be achieved.

Perception of Faces and Elaboration of Gender and Victim/Aggressor Stereotypes: The Influence of Internet Use and of the Perceiver's Personality.

The use of social media, particularly among youngsters, is characterized by simple and fast image exploration, mostly of people, particularly faces. The study presented here was conducted in order to investigate stereotypical judgments about men and women concerning past events of aggression-perpetrated or suffered-expressed on the basis of their faces, and gender-related differences in the judgments. To this aim, 185 participants answered a structured questionnaire online. The questionnaire contained 30 photos of young people's faces, 15 men and 15 women (Ma et al., 2015), selected on the basis of the neutrality of their expression, and participants were asked to rate each face with respect to masculinity/femininity, strength/weakness, and having a past of aggression, as a victim or as a perpetrator. Information about the empathic abilities and personality traits of participants were also collected. The results indicate that the stereotypes-both of gender and those of victims and perpetrators-emerge as a consequence of the visual exploration of faces that present no facial emotion. Some characteristics of the personality of the observers, such as neuroticism, extraversion, openness, conscientiousness, and affective empathy, have a role in facilitating or hindering stereotype processing, in different ways for male and female faces by male and female observers. In particular, both genders attribute their positive stereotypical attributes to same-gender faces: men see male faces as stronger, masculine, and more aggressive than women do, and women see female faces as more feminine, less weak, and less as victims than men do. Intensive use of social media emerges as a factor that could facilitate the expression of some stereotypes of violent experiences and considering female subjects as more aggressive. Findings in this study can contribute to research on aggressive behavior on the Internet and improve our understanding of the multiple factors involved in the elaboration of gender stereotypes relative to violent or victim behavior.

Allelic HLA Matching and Pair Origin Are Favorable Prognostic Factors for Unrelated Hematopoietic Stem Cell Transplantation in Neoplastic Hematologic Diseases: An Italian Analysis by the Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti.

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence.

Speed Overestimation of the Moving Away Object in the Intentional Reaction Causal Effect.

We describe a new illusory speed effect arising in visual events developed by Michotte (1946/1963) in studies of causal perception and, more specifically, within the so-called intentional reaction effect: When an Object B is seen intentionally escaping from another Object A, its perceived speed is overestimated. In Experiment 1, we used two-alternative forced choice comparisons to estimate perceived speed scale values for a small square moving either alone or in different contexts known to elicit different impressions of animacy (Parovel et al., 2018). The results showed that B's speed was overestimated only in the condition in which it moved away from another approaching square moving in a nonrigid way, like a caterpillar. In Experiment 2, we psychophysically measured the magnitude of speed overestimation in that condition and tested whether it could be affected by further animacy cues related to the escaping object (the actual velocity of the square) and to the approaching square (its type of motion: caterpillar or linear). Results confirmed that B's speed was overestimated up to 10% and that the degree of overestimation was affected by both experimental factors, being greater at higher speeds and when the chasing object moved in an animate fashion. This speed bias might be related to a higher sensitivity of the visual processes to threat-related events such as fighting and chasing, leading to evolutionary adaptive behaviours such as speedy flight from predators, but also empathy and emotion understanding.

Perceptions of Work-Related Stress and Ethical Misconduct Amongst Non-tenured Researchers in Italy.

The relationship between stress and unethical behaviour amongst non-tenured research staff in academia is a relatively unexplored phenomenon. The research reported herein was therefore carried out with the aim of exploring the relationship(s) between stress, the socio-organisational factors which contribute to it, job satisfaction, perceptions of job instability, and the occurrence of unethical behaviour in research. 793 Italian researchers participated in the research-all of whom were working on fixed-term contracts-after being individually requested to complete an online questionnaire. The data indicate that unethical behaviours occur with alarming frequency. The stress level reported is quite high, as is the level of perceived job insecurity, both of which impact upon levels of job satisfaction. Perceived stress levels also seem to play a role in the commission of unethical behaviours, but this relationship is irrelevant when one considers the role of social and organisational factors that are known to induce it. Indeed, it seems that there are various socio-organisational determinants of stress that have an obvious direct negative influence on the commission of unethical behaviours more than the stress level per se. This research paints a worrying picture in relation to the psycho-physical state of non-tenured researchers as a result of the working conditions in which they find themselves in Italian universities.

Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission: final results of quality of life and long-term outcome analysis of a phase 3 randomised study.

BACKGROUND: We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS). The aim of an extended follow-up study was the assessment of long-term outcomes, which are, in this context, scarcely reported in the literature. We report unpublished data on quality of life (QoL) from the original study and the results of a follow-up extension. METHODS: In the original open-label study, patients with acute myeloid and lymphoblastic leukaemia in first or subsequent remission, having sibling HLA-identical allogeneic peripheral blood stem-cell transplantation, were randomly assigned (1:1) to receive ATLG plus standard GVHD prophylaxis with ciclosporin and short-term methotrexate (ATLG group) or standard GVHD prophylaxis without ATLG (non-ATLG group). Conditioning regimens were cyclophosphamide 120 mg/kg with either total body irradiation (12 Gy) or busulfan (12·8 mg/kg intravenously or 16 mg/kg orally), with or without etoposide (30-60 mg/kg). Randomisation was stratified according to centre and disease risk. The primary endpoint was cumulative incidence of cGVHD at 2 years. The primary and secondary endpoints, excluding QoL, have been published. QoL, assessed using European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-HDC29 questionnaires, was an unpublished secondary endpoint, which we now report here. A follow-up extension was then done, with the primary endpoint cumulative incidence of cGVHD. Enrolment has been completed for both studies. The original trial (number, NCT00678275) and follow-up extension (number, NCT03042676) are registered at ClinicalTrials.gov. FINDINGS: In the original study, from Dec 14, 2006, to Feb 2, 2012, 161 patients were enrolled and 155 were randomly assigned to either the ATLG group (n=83) or to the non-ATLG group (n=72). In the follow-up study, which started on Feb 7, 2017, and was completed on June 30, 2017, 61 patients were included in the ATLG group and 53 were included in the non-ATLG group. Global health status showed a more favourable time course in the ATLG group compared with the non-ATLG group (p=0·02; treatment by visit interaction). ATLG was descriptively superior to non-ATLG at 24 months for physical function (points estimate -14·8 [95% CI -26·4 to -3·1]; p=0·014) and social function (-19·1 [-38·0 to -0·2]; p=0·047), gastrointestinal side-effects (8·8 [2·5-15·1]; p=0·008) and effect on family (13·5 [1·2-25·8]; p=0·032). Extended follow-up (median 5·9 years [IQR 1·7-7·9]) confirmed a lower 5-year cGVHD incidence (30·0% [95% CI 21·4-41·9] vs 69·1% [59·1-80·1]; analysis for entire follow-up, p<0·001), no increase in relapses (35·4% [26·4-47·5] vs 22·5% [14·6-34·7]; p=0·09), improved cGRFS (34·3% [24·2-44·5] vs 13·9% [7·1-22·9]; p=0·005), and fewer patients still in immunosuppression (9·6% vs 28·3%; p=0·017) in the ATLG group compared with the non-ATLG group. 5-year overall survival, relapse-free survival, and non-relapse mortality did not differ significantly between groups. INTERPRETATION: The addition of ATLG to standard GVHD prophylaxis improves the probability of surviving without disease relapse and cGVHD after myeloablative peripheral blood stem-cell transplantation from an HLA-identical sibling donor for patients with acute leukaemia in remission. Further additional benefits are better QoL and shorter immunosuppressive treatment compared with standard GVHD prophylaxis without ATLG. Therefore, in this setting, ATLG plus standard GVHD prophylaxis should be preferred over the standard GVHD prophylaxis alone. FUNDING: Neovii Biotech.

Complexity in internal medicine wards: A novel screening method and implications for management.

RATIONALE: Complexity is increasingly recognized as a critical variable in health care. However, there is still lack of practical tools to assess it and tackle the challenges that stem from it, particularly within hospitals. AIMS AND OBJECTIVE: To validate a simple novel screening method based on both objective and subjective criteria to identify patients with clinically complex hospitalization events. To evaluate the prevalence of patients with complex events, identify their features, and compare them with those of the other patients and to those of patients with multimorbidities. METHOD: We monitored the level of complexity of the hospitalization events of 240 patients admitted to an internal medicine ward in Tuscany over the course of 56 days. We compared the demographic features, the length of stay, and the prognosis of patients with and without complex events. RESULTS: Sixty-nine patients (28.8% of the sample) had a complex episode during their stay, and 115 (47.9%) had phases of low complexity. Patients with complex episodes were younger and more comorbid than patients without. They stayed longer in-hospital (+4.5 days; 95% CI: 2.5-6.5) and had higher mortality (OR: 24.93; 95% CI: 6.97-171.63) and a lower probability of home discharge (OR: 0.25; 95% CI: 0.13-0.48). CONCLUSIONS: The results show that using a simple screening method is possible to identify complex patients within IM wards and that every day, about one-third of the patients are complex. The results are discussed in implications for the dynamic management of patients with complex and simple phases during hospitalization.

Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases with Atypical Clinical Features Successfully Treated with Defibrotide.

Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both patients showed only a mild elevation in total serum bilirubin level. Most importantly, the two patients developed clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the diagnosis of VOD. Intravenous defibrotide was promptly started leading to a marked clinical improvement. Based on our experience, liver biopsy may represent a useful diagnostic tool when the clinical features of VOD are ambiguous. Early therapeutic intervention with defibrotide represents a crucial issue for the successful outcome of patients with VOD.

Access to alternative donor hematopoietic search and transplantation for acute leukemia in different macro-regions of Italy. A GITMO/IBMDR study.

Hematopoietic Stem Cell Transplantation activity levels vary across European countries. No data are available on the homogeneity of access to the transplant procedure for patient with leukaemia, within any European country. We measured homogeneity of the rate of alternative donor search in patients affected by acute leukaemia resident in each Italian region and macro-region during years 2010-2013. A total of 2747 alternative donor searches were studied. Twenty-one percent of all donor searches were made through extra-regional migration. Rate of alternative donor searches varied among the country's regions and macro-regions. The rate of donor searches was 38% lower in South Italy than in North Italy, and the rate of alternative donor transplantations performed was 45% lower. A reduced rate of alternative donor search in South macro-region was observed in all age cohorts. Despite the overall allogeneic transplant rate in Italy is relatively high, there are wide regional differences in access to transplant from alternative donor. Extra-regional migration cannot completely compensate for the lower access to transplant of acute leukaemia patients living in those regions where transplant activity is low.

Different contexts change the impression of animacy.

The aim of this research was to explore the effect of different spatiotemporal contexts on the perceptual saliency of animacy, and the extent of the relationship between animacy and other related properties such as emotions and intentionality. Paired-comparisons and ratings were used to compare the impressions of animacy elicited by a small square moving on the screen, either alone or in the context of a second square. The context element was either static or moving showing an animate-like or a physical-like trajectory, and the target object moved either toward it or away from it. The movement of the target could also include animacy cues (caterpillar-like expanding/contracting phases). To determine the effect of different contexts on the emergence of emotions and intentions, we also recorded and analysed the phenomenological reports of participants. The results show that the context significantly influences the perception of animacy, which is stronger in dynamic contexts than in static ones, and also when the target is moving away from the context element than when it is approaching it. The free reports reveal different proportions in emotional or intentional attributions in the different conditions: in particular, the "moving away" condition is related to negative emotions, while the "approaching" condition evokes positive emotions. Overall, the results suggest that animacy is a graded concept that can be articulated in more general characteristics, like simple aliveness, and more specific ones, like intentions or emotions, and that the spatiotemporal contingencies of the context play a crucial role in making them evident.

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey.

BACKGROUND: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. METHODS: We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. RESULTS: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). CONCLUSIONS: Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. CLINICAL TRIALS REGISTRATION: NCT02088840.

Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).

Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Fully automated, clinical-grade bone marrow processing: a single-centre experience.

BACKGROUND: Clinical grade processing of harvested bone marrow is required in various clinical situations, particularly in the management of ABO mismatching in allogeneic haematopoietic stem cell transplantation (HSCT) and in regenerative medicine. MATERIAL AND METHODS: We report a single-centre experience using a fully automated, clinical grade, closed system (Sepax, Biosafe, Switzerland). From 2003 to 2015, 125 procedures were performed in our laboratory, including buffy-coat production for HSCT (n=58), regenerative medicine in an orthopaedic setting (n=54) and density-gradient separation in a trial for treatment of critical limb ischaemia (n=13). RESULTS: Buffy coat separation resulted in a median volume reduction of 85% (range, 75-87%), providing satisfactory red blood cell depletion (69%, range 30-88%) and a median recovery of CD34 cells of 96% (range, 81-134%) in the setting of allogeneic HSCT. Significantly greater volume reduction (90%; range, 90-92%) and red blood cell depletion (88%; range, 80-93%) were achieved by the new SmartRedux software released for Sepax2, validated in the last eight allogeneic HSCT. The density gradient separation programme resulted in complete red blood cell depletion associated with high CD34 recovery (69%; range, 36-124%). No reactions related to the quality of the product were reported. Time to engraftment following allogeneic HSCT was in the normal range. No cases of microbiological contamination related to the manipulation were reported. DISCUSSION: Clinical grade, automated bone marrow manipulation with Sepax was shown to be effective, giving operator-independent results and could be used for a broad range of clinical applications.