Search

The endothelial activation and stress index (EASIX) score, calculated as [lactate dehydrogenase (LDH; U/L) × serum creatinine (mg/dL)]/platelets (10e9/L)], has been shown to be predictive of nonrelapse mortality (NRM) and endothelial complications in adults receiving allogeneic stem cell transplantation (allo-HSCT); however, definitive results are lacking for children. We retrospectively evaluated consecutive paediatric allo-HSCT recipients and calculated the log2 EASIX score every day from admission to day +35. In 167 allo-HSCT recipients, the EASIX score increased from before conditioning (-0.79) to a maximum score on day +20 (2.23). In multivariate analysis, the EASIX score at day +7 was an independent predictor of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) (OR 1.52; 95% CI, 1.08-2.13; p = 0.017) and NRM (OR 1.68; 95% CI 1.16-2.42; p = 0.006). At several time points between day +0 and day +14, the EASIX score was independently associated with NRM, with the strongest predictive power being observed on day +12 (OR 3.05; 95% CI, 1.53-6.10; p = 0.002). Age correlated linearly with the EASIX score at all analysed time points, but score prediction was confirmed even when age was added to the multivariate model, indicating that age was not a confounding factor in the observed associations. The EASIX score determined shortly after transplantation can be further explored as a predictor of SOS/VOD and NRM in paediatric allo-HSCT recipients., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT., Methods: This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up., Results: Ninety-four patients (63 males, 31 females, median age 10 years, range 1-21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87-68.97)., Conclusions: A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT., Competing Interests: Declaration of competing interest The Authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Steroid-refractory graft-versus-host disease (SR-GvHD) represents a major complication of pediatric allogenic hematopoietic stem cell transplantation. Ruxolitinib, a selective JAK 1-2 inhibitor, showed promising results in the treatment of SR-GvHD in adult trial, including patients >12 years old. This systematic review aims to evaluate ruxolitinib use for SR-GvHD in the pediatric population. Among the 12 studies included, ruxolitinib administration presented slight differences. Overall response rate (ORR) ranged from 45% to 100% in both acute and chronic GvHD. Complete response rates (CR) varied from 9% to 67% and from 0% to 28% in aGvHD and cGvHD, respectively. Individual-patient meta-analysis from 108 children under 12 years showed an ORR and CR for aGvHD of 74% and 56%, respectively, while in cGvHD ORR was 78% but with only 11% achieving CR. Treatment-related toxicities were observed in 20% of patients, including cytopenia, liver toxicity, and infections. Age, weight, graft source, previous lines of therapy, and dose did not significantly predict response, while a higher rate of toxicities was observed in aGvHD patients. In conclusion, ruxolitinib shows promising results in the treatment of SR-GvHD in children, including those under 12 years. Specific pediatric perspective trials are currently ongoing to definitely assess its efficacy and safety., (© 2024. The Author(s).)

Nutritional status plays a crucial role in the mortality rates of the pediatric oncology patients. However, there is a lack of systematic approaches for nutritional assessment in this population. This study aims to assess the current practice for nutritional assessment and care of pediatric cancer patients in Italy. A 25-items web-based, nation-wide questionnaire was circulated as of January 9, 2023 among physicians within the AIEOP network, composed of 49 national centers, out of which 21 routinely perform HCT. This survey examined the practices of 21 Italian pediatric oncology centers, revealing significant heterogeneity in nutritional practices. Only half of the centers routinely assessed all patients, utilizing different clinical and biochemical parameters. The use of neutropenic diets remained prevalent after chemotherapy or stem cell transplantation., Conclusion: This study underscores the pressing need for unified recommendations to improve nutritional care and potentially enhance outcomes for pediatric cancer patients., What Is Known: • The assessment and support of nutrition are gaining interest in the overall care of children with cancer. • The assessment and management of nutritional needs in pediatric cancer patients, including those undergoing hematopoietic cell transplantation, currently lack a systematic approach., What Is New: • There is considerable variability in the nutritional assessment and support among Italian centers treating pediatric patients with cancer. • To enhance nutritional assessment and support for pediatric cancer patients, it is essential to establish shared national and international guidelines., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report an unusual and confirmed case of invasive amebiasis in a non-endemic area where the source of infection remains unknown. During her admission, the patient developed amebic colitis and extraintestinal liver abscess with a favorable outcome following the antiparasitic therapy., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Systemic steroids are still the first-line approach in acute graft-versus-host disease (aGvHD), and the backbone of chronic GvHD management. Refractoriness to steroid represent a major cause of morbidity and non-relapse mortality after hematopoietic stem cell transplantation (HSCT). In both backgrounds, several second-line immunosuppressive agents have been tested with variable results in terms of efficacy and toxicity. Solid evidence regarding these approaches is still lacking in the pediatric setting where results are mainly derived from adult experiences. Furthermore, the number of treated patients is limited and the incidence of acute and chronic GvHD is lower, resulting in a very heterogeneous approach to this complication by pediatric hematologists. Some conventional therapies and anti-cytokine monoclonal antibodies used in the adult setting have been evaluated in children. In recent years, the increasing understanding of the biological mechanisms underpinning the pathogenesis of GvHD justified the efforts toward the adoption of targeted therapies and non-pharmacologic approaches, with higher response rates and lower immunosuppressive effects. Moreover, many questions regarding the precise timing and setting in which to integrate these new approaches remain unanswered. This Review aims to critically explore the current evidence regarding novel approaches to treat SR-GvHD in pediatric HSCT recipients., Competing Interests: The author (RM) declared that he was an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gottardi, Leardini, Muratore, Baccelli, Cerasi, Venturelli, Zanaroli, Belotti, Prete and Masetti.)

People with dementia have an increased risk of contracting severe forms of COVID-19. Although in worldwide vaccination programs priority has been given to older people, having taken the vaccine does not totally eliminate the risk of contracting COVID-19 when one is in close contact with unvaccinated people. Thus, family caregivers' choices to remain unvaccinated against COVID-19 could have potentially lethal consequences for their relatives. To our knowledge, this study represents the first attempt within the international literature to analyze COVID-19 vaccine uptake among family caregivers of people with dementia and to identify some of the psychological factors, related to COVID-19 and vaccination behavior, that could facilitate or hinder vaccine uptake. Contact information for family caregivers was obtained from five different centers and associations throughout the Italian territory. Data were collected from 179 respondents during July-September 2021 using a cross-sectional web-based survey design. More than 75% of the respondents indicated that had been vaccinated against COVID-19 and reported receiving vaccine information mainly from print or electronic newspapers (86%), followed by TV (81%) and families (64.2%). In multivariable logistic regression analyses, worries about unforeseen future effects was significantly related to COVID-19 vaccine uptake, indicating that family caregivers concerned about potential side effects of vaccines were less likely to have been vaccinated against COVID-19 (OR = 0.60, CI = 0.40-0.89). Openness to experience was also related to COVID-19 vaccine uptake, with family caregivers higher on this trait being less likely to have been vaccinated against COVID-19 (OR = 0.83, CI = 0.71-0.98). Implications for targeting of vaccine-related messages are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruno, Malvaso, Chiesi, Laganà, Servidio, Isella, Ferrarese, Gottardi, Stella, Agosta, Filippi, Lorenzo, Martin, Bruni and Maletta.)

Treatment of refractory autoimmune cytopenias (AICs) and Evans syndrome (ES) represent a great challenge in pediatric setting, where an underlying primary immunodeficiency is recurrent. Frequently, second or third line treatments are employed, with an increased risk of toxicity and infections. The advent of novel drugs is the object of research in order to modify the management of these patients.We report a case of successful use of bortezomib in a child with 22q11.2 deletion syndrome and CVID-like phenotype with a multi-refractory severe ES. Last flares were prolonged and dominated by severe and symptomatic ITP, refractory to different courses of high dose steroid and IVIG, mofetil mycophenolate, thrombopoietin receptor agonists, sirolimus, and rituximab. Persistence of AICs in subjects with depletion of CD20 + B-cells and IgG strengthens the hypothesis about the production of autoantibodies by terminally differentiated plasma-cells, not targetable from immunosuppressants and rituximab.In the attempt to enhance plasma-cells inhibition, the child was addressed to bortezomib, with a good response at 6 month follow-up without side effects. Nowadays, the use of bortezomib in ES/AICs is based only on small retrospective studies and case reports. Despite the lack of long term follow-up, our work highlights the potential role of bortezomib in the management of pediatric patients with multi-resistant AICs secondary to immune-system impairment.

Febrile neutropenia (FN) is a common complication in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella , Megasphaera , Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called "healthy" GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications.

Saffron is one of the most adulterated food products all over the world because of its high market prize. Therefore, a non-targeted approach based on the combination of headspace flash gas-chromatography with flame ionization detection (HS-GC-FID) and chemometrics was tested and evaluated to check adulteration of this spice with two of the principal plant-derived adulterants: turmeric ( Curcuma longa L.) and marigold ( Calendula officinalis L.). Chemometric models were carried out through both linear discriminant analysis (LDA) and partial least squares discriminant analysis (PLS-DA) from the gas-chromatographic data. These models were also validated by cross validation (CV) and external validation, which were performed by testing both models on pure spices and artificial mixtures capable of simulating adulterations of saffron with the two adulterants examined. These models gave back satisfactory results. Indeed, both models showed functional internal and external prediction ability. The achieved results point out that the method based on a combination of chemometrics with gas-chromatography may provide a rapid and low-cost screening method for the authentication of saffron.

Objective: Stroke is an important risk factor for dementia, but the exact mechanism involved in cognitive decline remains unclear., Methods: Patients were divided into 2 groups: poststroke dementia group (PSD) and poststroke nondementia group (PSND). Variables and neuroradiological hallmarks were compared between 2 groups at 3 months (114 subjects) and 1 year (105 subjects) after stroke., Results: Older age (OR 1.11, 95% CI 1.0-1.2; P < .05), education (OR .6, 95% CI .4-.8; P < .05), prestroke IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly; OR .78, 95% CI .1-5.9; P < .05), premorbid apathy (OR 2.03, 95% CI 1.1-3.7; P < .05), and medial temporal lobe atrophy (MTLA) (OR 6.14, 95% CI 1.4-26.2; P < .05) were independently associated with PSD at 3 months after a cerebrovascular event, whereas at 1-year follow-up older age (OR 1.1, 95% CI 1.0-1.2; P < .05), prestroke IQCODE (OR .05, 95% CI .0-.9; P < .05), MTLA (OR 1.3, 95% CI 1.0-1.6; P < .05), and APACHE II (Acute Physiology and Chronic Health Evaluation; OR .6, 95% CI .4-.9; P < .05) were independently associated with PSD., Conclusions: Acute cerebrovascular disease could not be the only one mechanism explaining PSD. Neurodegenerative pathology must be taken into account., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: In current Alzheimer disease (AD) research there is growing asymmetry between the modest benefits of the currently available treatments, in contrast to the possibility to diagnose AD early in its natural history. This complex situation brings along a number of important ethical issues about diagnosis disclosure and end-of-life decisions that need to be addressed. The principal aim of the study was to investigate the attitudes towards disclosure of a diagnosis of AD and disposition towards completion of advance care planning, in a sample of Italian citizens., Methods: A convenience sample of 1,111 Italian citizens recruited from a community hospital in Brescia were interviewed using a structured questionnaire with both yes/no and multiple choice format questions about AD., Results: The majority of the sample (83 %) wanted disclosure for themselves. Women and caregivers were significantly less likely to agree that their hypothetically afflicted relative should be informed of a diagnosis of AD. The majority of the sample (81 %) was in favor of advance care planning completion, most of all younger participants and non-caregivers. Less than a third of the sample (24 %) was aware of the existence a judicially appointed guardian for patients affected by dementia., Conclusion: The majority of the participants wanted a potential diagnosis of AD to be disclosed to them and to their relatives if they were to be afflicted. The utility of completion of advance care planning and designation of a judicially appointed guardian is frequently endorsed by the sample.

Objective: To examine the usefulness of specific neurocognitive tests for predicting the crash involvement in ultra-octogenarian population., Methods: A total of 800 subjects (mean age 82.4 + 3.1 years) underwent a battery of neuropsychological tests. Global intellectual functioning was assessed using the Mini Mental State Examination, mental flexibility and information processing speed were assessed using the Trail Making Test parts A and B (TMT-A and TMT-B), long-term memory was evaluated with the short story, and visuo-spatial skills were tested with Clock Drawing Test. One year after this evaluation, 343 (43%) participants have been interviewed by a telephone call to know if they were currently driving and if they had a car crash during this period., Results: Two hundred ninety-seven subjects had their driving license renewed and completed the follow-up 1 year after. Data shows that less than 11% of this group had a car crash during the first year of observation (Crash Involved). Older subjects involved in a car crash showed significant worse performances on TMT-B (TMT-B pathological Crash Involved vs. Noncrash Involved 47% vs. 27%; p = 0.02) and on short story (short story pathological Crash Involved vs. Noncrash Involved 19% vs. 5%; p = 0.02)., Conclusions: Trail Making test B and short story have been demonstrated to provide a predictive value of driving performance of older people. Therefore, we suggest that a simple and standardized battery of neuropsychological tests, lasting about 30 min and administered by an experienced staff, is a good diagnostic instrument for risk prevention of driving activity of older drivers., (Copyright © 2012 John Wiley & Sons, Ltd.)