Purpose
Bloodstream infections (BSIs) are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to identify predictors of mortality after BSI in ...patients who undergo HSCT.
Methods
Patients who underwent HSCT between 1 January 2004 and 31 January 2008 and developed BSI during the first year post-transplantation were included. Variables influencing overall mortality at 7 and 30 days after BSI were analysed.
Results
BSIs developed in 149 patients, within a median of 9 days after undergoing HSCT. Early and late mortality were 15 and 27%, respectively. Of the BSI, 54% were due to Gram-positive microorganisms, 33% were due to Gram-negative microogranisms, 10% were polymicrobial and 3% were fungal. The associated 7-and 30-day mortality was respectively 10 and 24% (Gram positive), 22 and 31% (Gram negative;
Pseudomonas aeruginosa
mortality 67%, all within 7 days), 13 and 27% (polymicrobial) and 40% (fungal, all within 7 days). Early mortality was higher in relapsed disease at HSCT (25.9%,
p
= 0.01), but lower in early (i.e. within 20 days of HSCT) BSI (11.7%,
p
= 0.03) and BSI due to Gram-positive infective agents (10%,
p
= 0.05). Multivariate analysis confirmed a higher mortality in late BSI odds ratio (OR) 3.29,
p
= 0.03 and relapsed disease at HSCT (OR 2.2,
p
= 0.04). Late mortality was associated with the type of underlying disease (OR 0.44 for diseases other than acute leukaemia,
p
= 0.05) and its status (OR 6.04 for relapse at HSCT,
p
= 0.001). Appropriate empirical therapy was associated with lower early and late mortality in single Gram-negative BSI (16 vs. 45% for 7-day mortality,
p
= 0.09; 21 vs. 64% for 30-day mortality,
p
= 0.02).
Conclusions
BSIs are frequent during the first year after HSCT and are associated with a high mortality rate. The aetiology influenced early mortality, while the type and phase of the underlying disease played a pivotal role in late mortality. Appropriate empirical therapy is crucial in BSI due to Gram-negative infective agents.
•A novel image pre-processing algorithm is proposed for PIV.•The method is based on Proper Orthogonal Decomposition.•Theoretical background and validation are presented.•Background noise with large ...intensity, gradients, and time oscillation is eliminated.
State-of-art preprocessing methods for Particle Image Velocimetry (PIV) are severely challenged by time-dependent light reflections and strongly non-uniform background. In this work, a novel image preprocessing method is proposed. The method is based on the Proper Orthogonal Decomposition (POD) of the image recording sequence and exploits the different spatial and temporal coherence of background and particles. After describing the theoretical framework, the method is tested on synthetic and experimental images, and compared with well-known pre-processing techniques in terms of image quality enhancement, improvements in the PIV interrogation and computational cost. The results show that, unlike existing techniques, the proposed method is robust in the presence of significant background noise intensity, gradients, and temporal oscillations. Moreover, the computational cost is one to two orders of magnitude lower than conventional image normalization methods. A downloadable version of the preprocessing toolbox has been made available at http://seis.bris.ac.uk/~aexrt/PIVPODPreprocessing/.
Pectin methylesterase inhibitor Giovane, A.; Servillo, L.; Balestrieri, C. ...
BBA - Proteins and Proteomics,
02/2004, Letnik:
1696, Številka:
2
Book Review, Journal Article
Recenzirano
Pectin methylesterase (PME) is the first enzyme acting on pectin, a major component of plant cell wall. PME action produces pectin with different structural and functional properties, having an ...important role in plant physiology. Regulation of plant PME activity is obtained by the differential expression of several isoforms in different tissues and developmental stages and by subtle modifications of cell wall local pH. Inhibitory activities from various plant sources have also been reported. A proteinaceous inhibitor of PME (PMEI) has been purified from kiwi fruit. The kiwi PMEI is active against plant PMEs, forming a 1:1 non-covalent complex. The polypeptide chain comprises 152 amino acid residues and contains five Cys residues, four of which are connected by disulfide bridges, first to second and third to fourth. The sequence shows significant similarity with the N-terminal pro-peptides of plant PME, and with plant invertase inhibitors. In particular, the four Cys residues involved in disulfide bridges are conserved. On the basis of amino acid sequence similarity and Cys residues conservation, a large protein family including PMEI, invertase inhibitors and related proteins of unknown function has been identified. The presence of at least two sequences in the
Arabidopsis genome having high similarity with kiwi PMEI suggests the ubiquitous presence of this inhibitor. PMEI has an interest in food industry as inhibitor of endogenous PME, responsible for phase separation and cloud loss in fruit juice manufacturing. Affinity chromatography on resin-bound PMEI can also be used to concentrate and detect residual PME activity in fruit and vegetable products.
M. Mikulska, V. Del Bono, R. Prinapori, L. Boni, A.M. Raiola, F. Gualandi, M.T. Van Lint, A. Dominietto, T. Lamparelli, P. Cappellano, A. Bacigalupo, C. Viscoli. Risk factors for enterococcal ...bacteremia in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2010: 12: 505–512. All rights reserved
: Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case–control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2–24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65–48.99 and OR=7.52, 95% CI, 1.56–36.31, respectively, P=0.047); severe (grades 3–4) mucositis (OR=9.04, 95% CI, 1.97–41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11–18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93–18.66 for 1–7 days of therapy, and OR=7.31, 95% CI, 1.78–30.12 for 8–23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06–0.97, P=0.045 and OR=0.11, 95% CI, 0.02–0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.
Retinal vein occlusions (RVOs) are rare in the younger population. Hematological pro-thrombotic factors are thought to be important in a minority, amplifying an atherosclerotic anatomical ...predisposition.
Anotherwise healthy 13-year-old girl presented two episodes of sudden decreased vision in few months.Ophthalmological exams pointed out post-thrombotic intra-retinal hemorrhage. All investigations were normal, thrombophilia screen showed factor XII deficiency and genetic mutations of methylenetetrahydrofolate reductase (MTHFR), angiotesin convertin enzyme (ACE) and angiotensinogen (AGT). Two intravitreal injection of bevacizumab was administered with improving visual acuity; subsequently the patient did not report further episodes.
In addition to traditional factors with procoagulant activity, factor XII deficiency plays an important role in thrombosis's mechanism. Its deficiency causes a marked prolongation of the activated partial thromboplastin time in the laboratory examination. Moreover also MTHFR, ACE and AGT could have been involved in this case, so it is important to evaluate these parameters in the differential diagnosis of RVOs.
Transplant‐related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning ...in 33 patients with a median age of 52 years (range 43–60) transplanted from human leucocyte antigen (HLA)‐identical siblings. The underlying disease was chronic myeloid leukaemia (n = 15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The regimen consisted of thiotepa (THIO; 10 mg/kg) on day −5 and cyclophosphamide (CY; 50 mg/kg) on days −3 and −2 (total dose 100 mg/kg). The source was bone marrow (BM) (n = 17) or granulocyte colony‐stimulating factor (G‐CSF)‐mobilized peripheral blood (PB) (n = 16), which were infused without manipulation. Graft‐versus‐host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a short course of methotrexate. Mean time to achieve a neutrophil count of 0·5 × 109/l was 17 d (range 11–23) and full donor chimaerism was detected in 79% of patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients. Chronic GVHD was seen in 45% of patients, with a significant difference for PB (69%) compared with BM transplants (23%) (P = 0·009). For BM grafts, the actuarial 2‐year TRM was 6%, the relapse 56% and survival 87%; for PB grafts, these figures were, respectively, 27%, 33% and 68%. Twenty‐five patients are alive at a median follow‐up of 762 d (range 216–1615) and 20 patients (60%) remain free of disease. Thirteen patients (39%) received donor lymphocyte infusion (DLI) either for persisting or relapsing disease and six patients had complete remission. In conclusion: (i) patients up to the age of 60 years can be allografted with reduced intensity conditioning; (ii) the procedure was associated with a low transplant‐related mortality, particularly for bone marrow grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required after transplant in half the patients for persisting disease or relapse.
We assessed the outcome of 170 patients with AML in first complete remission, aged 1-47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all ...patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.
Platelet recovery after allogeneic haemopoietic stem cell transplant (HSCT) and predictive factors were analysed in 342 patients with haematological malignancies. All patients were prepared with ...cyclophosphamide plus total body irradiation, and received an unmanipulated HSCT from an HLA‐identical sibling (n = 270), a matched unrelated donor (n = 67) or an identical twin (n = 5). The source of stem cells was peripheral blood (n = 15) or bone marrow (n = 327). Graft‐vs.‐host disease (GvHD) prophylaxis consisted of cyclosporin A with or without methotrexate. The proportion of patients with < 50 × 109/l platelets on d +50, d +100, d +200 and d +365 after HSCT was 26%, 27%, 14% and 11% respectively. Thrombocytopenia was independent of the degree of complete donor chimaerism. Four variables were predictive of platelet recovery: donor type, acute GvHD, cytomegalovirus (CMV) infection and number of cells infused at transplant. Recipients of an unrelated graft had lower platelet counts (49 × 109/l) on d +50 than identical sibling grafts (108 × 109/l) (P < 0·001) and twin grafts (149 × 109/l) (P < 0·001). Patients with GvHD grades 0, I, II, III and IV had significantly different platelet counts on d +50 (153 × 109/l, 102 × 109/l, 85 × 109/l, 32 × 109/l and 22 × 109/l; P < 0·001) and thereafter. Thrombocytopenia was more frequent in patients with high‐level CMV antigenaemia (> four positive cells/2 × 105) (P < 0·0001) and in patients who received a low cell dose at transplant (≤ 4·1 × 108/kg) (P = 0·009). Platelet counts predicted transplant‐related mortality (TRM) and were higher at all time intervals in patients surviving the transplant. Patients with grade II GvHD and > 50 × 109/l platelets had a lower TRM than patients with grade II GvHD and ≤ 50 × 109/l platelets (14% vs. 40%, P < 0·0001).
In conclusion, (i) a significant proportion of allogeneic HSCT recipients are thrombocytopenic long‐term, irrespective of complete donor chimaerism, (ii) thrombocytopenia identifies patients at greater risk of lethal complications, and (iii) platelet recovery is influenced by GvHD, donor type, CMV infections and cell dose, not by stem cell source or other patient–disease‐related variables.
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