Aims
Multidrug‐resistant (MDR) bacteria are an emerging cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). The aim of the study was to analyse the incidence, ...clinical characteristics and survival from bacterial infections (BI) caused by MDR pathogens in paediatric HSCT recipients.
Methods and Results
Among 971 transplanted patients, BI were found in 416 children between the years 2012 and 2017. Overall, there were 883 bacterial episodes, which includes 85·8% after allo‐HSCT and 14·2% after auto‐HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections.
Conclusions
Regarding HSCT type, we did not find differences in the profile of MDR BI between allo‐ and auto‐HSCT recipients. However, survival in MDR and non‐MDR infections was comparable.
Significance and Impact of the Study
The large sample size enables unique analysis and makes our data more applicable to other paediatric HSCT centres. In the absence of local epidemiological data, presented clinical characteristics of MDR‐caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR aetiology and thus promptly initiate adequate antibiotic therapy and further improve patients’ outcome.
We analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, ...over a 2-year period.
Hospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI). The majority of patients (40/67; 59.7%) underwent HSCT from matched unrelated donors (MUD).
In total, 84 BI in 31 patients, 93 VI in 50 patients, and 27 FI in 22 patients were diagnosed. No differences were found in the frequency of occurrence of BI according to the type of transplant (P = .16); the occurrence of VI was statistically more frequent in MUD transplant recipients as compared with matched sibling donors (MSD) and mismatched related donors (MMFD; P = .001) and there was a trend in MUD patients for the higher occurrence of FI in comparison with MSD and MMFD transplants (P = .08). Regarding disease status, the occurrence of BI, VI, and FI was statistically more frequent in children who underwent transplantation in their first complete remission (CR1), rather than those who underwent transplantation in ≥CR2 (P < .05). In conclusion, infectious complications are an important cause of morbidity in children with ALL treated with allogeneic HSCT and the incidence of infections is high in this group of patients.
•We analyzed the incidence and profile of infections in children with ALL following HSCT.•No differences were found between the occurrence of BI and donor type.•Statistically there was a higher occurrence of VI in unrelated donor transplants.•There was a trend of higher occurrence of FI in unrelated donor transplants.•There was a more frequent occurrence of infectious complications in children who underwent transplantation in CR1.
Abstract Introduction Steroid-refractory graft-versus-host disease (GVHD) remains a challenging therapeutic problem after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this ...study was to evaluate the clinical effect of extracorporeal photopheresis (ECP), and its impact on intensivity of immunosuppresive therapy in allogeneic HSCT patients. Patients and Methods In this study 443 Therakos ECP procedures were performed in 21 patients after allogeneic HSCT with acute (aGVHD, 8 patients) or chronic (cGVHD, 13 patients) therapy-refractory GVHD. The median age at ECP onset was 20.5 years (range, 10–55). Venous access was provided by a nontunelized central venous catheter (12 patients) or 9.6-French portacath (9 patients). Results In the cGVHD group 9/13 patients were improved with a 4-year overall survival rate of 67.7%. ECP led to steroid discontinuation in 6 and substantial dose reduction in 5 patients. The prednisone dose equivalent per kilogram body weight decreased from 0.32 mg to 0.07 mg after therapy. Therapy of aGVHD led to complete or partial symptom remission in 3/9 subjects. The change in steroid dose in the aGVHD group was not significant, there were no long-term survivors. Portacath access was well tolerated and provided adequate blood flow rates. Conclusions The ECP therapy significantly reduced the rates of remissions with steroid discontinuation among cGVHD but not aGVHD patients. Rare ECP-related complications were either catheter related or anticoagulation induced during ECP procedures. Photopheresis was a safe, effective method to treat steroid-resistant cGVHD.
This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic ...SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n=24) or matched unrelated (MUD) (n=27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m(2) (n=21) or 36-42 g/m(2) (n=30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.
Background
Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo‐HSCT) because of delayed immune reconstitution ...and graft‐versus‐host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients.
Objective
The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012–2013.
Patients and methods
In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02–22 years (median age: 7 years), 92 after allo‐HSCT and 22 after autologous HSCT (auto‐HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug‐resistant organisms, and impact of underlying disease and of graft‐versus‐host disease on BI episodes.
Results
In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo‐HSCT and 36 after auto‐HSCT. Among allo‐HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor‐HSCT 0.3; matched donor‐HSCT 0.4; mismatched unrelated donor MMUD‐HSCT 0.8; P = 0.027) and after auto‐HSCT 0.3 per 1 transplanted patient. In patient after allo‐HSCT because of myelo‐ or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram‐positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto‐HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly.
Conclusions
The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD‐HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram‐negative bacteria predominated in patients with myelo‐ and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram‐positive strains were predominant.
Abstract Late-onset hemorrhagic cystitis (HC) caused by adenovirus (AdV) infection is a common complication in hematopoietic stem cell transplantation (HSCT) recipients. However, limited information ...exists regarding adenovirus-associated HC. We report a retrospective study of 84 hematopoietic stem cell transplant recipients that evaluated the incidence and risk factors for AdV-induced HC. The development of HC was strongly related to adenoviral infection ( P = .004). Among 13 patients who developed late-onset HC, AdVs were identified as a causative agent in 10 cases. AdV preferentially affected younger ( P = .013) and male patients. Affected subjects had been transplanted for either malignant (7/10) or nonmalignant disorders (3/10). Most cases of AdV-hematuria were self-limited single or recurrent mild hemorrhagic episodes ( P = .000), occuring at a median of 41 days after transplantation and lasting an average of 4 days. Viral load in patients with AdV-induced HC was similar to infected subjects who did not develop HC (2.5 × 103 vs 3.4 × 103 copies/mL). We HC occurring before 200 days was associated with a greater risk of a fatal outcome ( P = .002) but occurrence of AdV infection did not affect a patient's survival. Our study confirmed the suggestion that non-AdV coinfections may worsen the course of AdV-HC.
Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NFκB) in maternal ...and placental cells. Although the role of NFκB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NFκB activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NFκB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NFκB activation. One such pathway depends on the activation of NFκB by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNFκB Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNFκB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53/RSK1 complex might play a critical role in the activation of NFκB in trophoblastic cells and preeclamptic placentas.
Brown bears (Ursus arctos L., 1758) damage trees (mainly the cambium) during feeding and marking. It is thought that their stripping of bark and their subsequent foraging on sapwood can lead to ...substantial economic losses. However, the part played by this process in the ecosystem is still unknown. We hypothesize that brown bear foraging makes resources and habitats available to other species. We anticipated that wounds perpetrated by bears during foraging would attract saproxylic insects and consequently insectivorous birds. Bear wounds were searched for on trees in the Bieszczady Mountains (Polish Eastern Carpathians) from 2008 to 2011. We analyzed 278 wounds in silver firs (Abies alba Mill.) of different age classes: 43% of them had holes made by wood-boring insects and 33% had signs of woodpecker feeding. The presence of insect holes and woodpecker marks in the wound was found to depend on wound area, wound age, and tree circumference (insects only). In particular, the oldest wound age class (>5 years old) was associated with a high probability of occurrence of insects and woodpeckers. Insects were attracted by wounds of smaller area than woodpeckers. The density of insect holes (number of wood-boring insects) depended on the wound age and tree circumference. Insect densities in fresh wounds (<1 year old) were significantly lower than in the older age classes. The results show that bear-made wounds provide breeding and feeding sites for both insects and birds. Especially for woodpeckers (forest indicator species) and for saproxylic insects (mainly endangered species), brown bears may play an important role as niche constructors and ecological engineers. Therefore, it would be advisable to leave a considerable number of bear-wounded trees in the forest ecosystems for conservation purposes.
•Six tree species: fir, larch, spruce, pine, beech, and ash – were damaged by bears.•Conifers tree species were more frequently damaged than deciduous.•Mean forage ratio was higher for larch than for ...fir, spruce and pine.•The improvement in fir condition and the bear numbers had influence on damage scale.•Tree damage by bears is not a substantial problem for forest management in Poland.
We present a long-term quantitative analysis of forest damage caused by the brown bear (Ursus arctos) in the biggest refuge of this species in Poland. Based on questionnaires distributed to the relevant authorities we estimated the number of trees damaged by bears in 1991–2013, changes in the tree species composition and large-scale factors potentially affecting the extent of damage. We also discuss the importance of bear tree damage to forest management. Throughout the 23years of the study we recorded 6937 trees damaged by bears: a clearly increasing trend and distinct fluctuations in tree numbers and species composition were discernible. Conifers (91.7% – fir 70.0%, larch 11.3%, spruce 9.5%, pine 0.9%) were more frequently damaged than deciduous species (2.9%). Larch and spruce were preferentially affected during the whole study period, and the preference for larch was distinct when collated with its availability in forest stands – a forage ratio of 0.50 compared to 0.35 for fir, 0.17 for spruce and 0.13 for pine. In 2003, however, bears suddenly switched to fir and it is this species that now predominates among the damaged trees, reaching 96.5% in 2013.
Two models based on minimum AICc values were best explaining damage to trees. The most parsimonious model contained one explanatory variable: brown bear population size. The second best model included both bear population size and the average fir tree-ring width. Neither fluctuations in daily temperatures nor the number of days with snow cover had any influence on the scale of damage. Our findings suggest that damage caused by bears is not to be regarded as a serious problem by forest management in Poland and it is unlikely to reach a level of economic significance in the short term.
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