218 research outputs found
G-CSFâstimulated Neutrophils Are a Prominent Source of Functional BLyS
B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNÎł, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSFâstimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by antiâG-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis
Transapical off-pump echo-guided mitral valve repair with neochordae implantation mid-term outcomes
Background: The NeoChord echo-guided transapical beating heart repair is a promising early-stage
minimally invasive surgical procedure for degenerative mitral valve (MV) regurgitation (DMR) correction.
The technique has been improved since its inception following procedure standardization, patient selection
optimization, and learning curve stabilization. We hereby present the mid-term clinical results through three
years of our large single center experience.
Methods: All consecutive patients with severe symptomatic DMR due to prolapse or flail of one or both
mitral leaflets that underwent the NeoChord procedure between November 2013 and June 2019 were
included. Patients were categorized according to MV anatomy; Type A isolated central posterior leaflet
prolapse and/or flail, Type B posterior multi-segment prolapse and/or flail, Type C anterior and/or bi-leaflet
prolapse or flail, Type D paracommissural prolapse and/or flail and/or significant leaflet and/or annular
calcifications. Patients underwent clinical and echocardiographic follow-up at one, three, six, twelve months
and yearly thereafter. Clinical outcomes and the composite primary endpoint (patient success) were defined
according to Mitral Valve Academic Research Consortium (MVARC) criteria. Mitral regurgitation (MR)
severity was graded as absent, mild, moderate and severe according to American Society of Echocardiography
(ASE) and European Society of Cardiology (ESC) guidelines.
Results: Two hundred and three patients were included; median follow-up was 24 months [interquartile
range (IQR), 9â36]. Median age was 64 years (IQR, 54â74 years), median Society of Thoracic Surgeons
(STS) Predicted Risk of Mortality (PROM) was 0.60% (IQR, 0.32â1.44%). There were 106 Type A patients
(52.2%), 68 Type B (33.5%), 16 Type C (7.9%), and 13 Type D (6.4%). Kaplan-Meier estimate of survival
was 99.0%±0.7% at one and two years and 94.0%±2.9% at three years. At one-year follow-up patient success
was 91.2%±2.0% and 111 patients (74%) presented a residual MR mild or less (1+). At three-year follow-up
patient success was 81.2%±3.8% and 32 patients (64%) had a residual MR mild or less (1+). Patient success
was significantly different according to anatomical type (P=0.001). Echocardiographic analysis showed a
significant acute left ventricle and left atrial reverse remodeling that was maintained up to three years.
Conclusions: The NeoChord echo-guided transapical beating heart repair procedure demonstrated good
clinical outcomes and echocardiographic results up to three-year follow-up
Business and Information Technology Alignment Measurement -- a recent Literature Review
Since technology has been involved in the business context, Business and
Information Technology Alignment (BITA) has been one of the main concerns of IT
and Business executives and directors due to its importance to overall company
performance, especially today in the age of digital transformation. Several
models and frameworks have been developed for BITA implementation and for
measuring their level of success, each one with a different approach to this
desired state. The BITA measurement is one of the main decision-making tools in
the strategic domain of companies. In general, the classical-internal alignment
is the most measured domain and the external environment evolution alignment is
the least measured. This literature review aims to characterize and analyze
current research on BITA measurement with a comprehensive view of the works
published over the last 15 years to identify potential gaps and future areas of
research in the field.Comment: 12 pages, Preprint version, BIS 2018 International Workshops, Berlin,
Germany, July 18 to 20, 2018, Revised Paper
Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey.
OBJECTIVES:
To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis.
METHODS:
From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925.
RESULTS:
In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, âŒ30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities.
CONCLUSIONS:
This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used
Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorfism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation
BACKGROUND: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. PATIENTS AND METHODS: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. RESULTS: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. CONCLUSION: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients
Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study
We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib
'Real-life' analysis of the role of antifungal prophylaxis in preventing invasive aspergillosis in AML patients undergoing consolidation therapy: Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM) 2016 study.
Febrile events in acute lymphoblastic leukemia: a prospective observational multicentric SEIFEM study (SEIFEM-2012/B ALL).
Changes in the incidence of candidemia and related mortality in patients with hematologic malignancies in the last ten years. A SEIFEM 2015-B report
Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper
The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections
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