Outcome of Hematopoietic Stem Cell Transplantation in 813 Pediatric Patients with Fanconi Anemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA) associated bone marrow failure (BMF)/aplastic anemia (AA) and hematological malignancy. We performed a retrospective multicenter study on 813 FA children undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years (interquartile range, 3.4-4.0). Median age at transplant was 8.8 years (6.5-18.1). Overall survival (OS), event-free survival (EFS) and GvHD-free, relapse-free survival (GRFS) at 5 years were 83% (80-86%), 78% (75-81%) and 70% (67-74%) respectively. OS was comparable between matched family donor (MFD, n=441, 88%) and matched unrelated donor (MUD, n=162, 86%) and was superior to that of mismatched family or unrelated donor (MMFD/MMUD, n=144, 72%) and haploidentical donor (HID) (n=66, 70%, p<0.001). In multivariable analysis, a transplant indication of acute myeloid leukaemia/myelodysplastic syndrome compared to AA/BMF, use of MMFD/MMUD and HID compared to MFD, Fludarabine-Cyclophosphamide (FluCy) + other conditioning compared to FluCy independently predicted inferior OS, while alemtuzumab compared to ATG was associated with better OS. Age  10 years was associated with worse EFS and GRFS. Cumulative incidences (CIN) of primary and secondary graft failure were 2% (1-3%) and 3% (2-4%) respectively. CIN of grade II-IV acute GvHD, grade III-IV acute GvHD and chronic GvHD were 23% (20-26%), 12% (10-15%) and 8% (6-10%) respectively. The 5-year CIN of secondary malignancy was 2% (1-3%). These data suggest that HSCT should be offered to Fanconi Anemia patients with AA/BMF at a younger age in the presence of a well-matched donor.

Subtypes and location of (juxta)cortical lesions relate to cognitive dysfunction in people with multiple sclerosis.

BACKGROUND: Cortical lesion subtypes' occurrence and distribution across networks may shed light on cognitive impairment (CI) in multiple sclerosis (MS). METHODS: In 332 people with MS, lesions were classified as intracortical, leukocortical or juxtacortical based on artificially generated double inversion-recovery images. RESULTS: CI-related leukocortical lesion count increases were greatest within sensorimotor and cognitive networks (p < 0.001). Only intracortical lesion count could distinguish between cognitive groups (p = 0.024). Effect sizes were two- to four-fold larger than differences between MS phenotypes. CONCLUSION: In CI-MS, leukocortical lesions predominate, whereas intracortical lesions distinguish cognitive groups. Lesions' grey matter (GM) involvement might be decisive for cognition in MS, surpassing overall disease burden.

Brief admission by self-referral as an add-on to usual care for individuals with self-harm at risk of suicide: cost-effectiveness and 4-year health-economic consequences after a Swedish randomized controlled trial.

BACKGROUND: Brief Admission by self-referral (BA) is a crisis-management intervention standardized for individuals with self-harm at risk of suicide. We analyzed its health-economic consequences. MATERIALS AND METHODS: BA plus treatment as usual (TAU) was compared with TAU alone in a 12-month randomized controlled trial with 117 participants regarding costs for hospital admissions, coercive measures, emergency care and health outcomes (quality-adjusted life years; QALYs). Participants were followed from 12 months before baseline to up to five years after. RESULTS: Over one year BA was associated with a mean annual cost reduction of 4800 or incremental cost of 4600 euros, depending on bed occupancy assumption. Cost-savings were greatest for individuals with >180 admission days in the year before baseline. In terms of health outcomes BA was associated with a QALY gain of 0.078. Uncertainty analyses indicated a significant QALY gain and ambiguity in costs, resulting in BA either dominating TAU or costing 59 000 euros per gained QALY. CONCLUSION: BA is likely to produce QALY gains for individuals living with self-harm and suicidality. Cost-effectiveness depends on targeting high-need individuals and comparable bed utilization between BA and other psychiatric admissions. Future research should elaborate the explanatory factors for individual variations in the usage and benefit of BA.

The Interaction of Cannabis Consumption with Heavy Episodic Drinking and Alcohol-induced Blackouts in Relation to Cannabis Use Consequences Among Recent Undergraduate College Cannabis Users.

Introduction: Risky alcohol use patterns, characterized by heavy episodic drinking (HED) and alcohol-induced blackout, are prevalent in college students. However, it is not clear if experiencing HED and blackout among college-attending cannabis users heightens risk for adverse cannabis use consequences. The purpose of this study was to examine whether heavy episodic drinking and blackout episodes moderate the relationship between cannabis consumption and cannabis use consequences among college students. Methods: Undergraduate college students (n = 4331) were recruited from a Midwest University in 2021. This analysis used a subset of data from past 6-month cannabis users (n= 772; 17.8% of the full sample). Among cannabis users, 64.5% identified as female and 87.8% were White with an average age of 19.99 (SD=2.88). A linear regression was conducted with two two-way interactions of cannabis consumption and HED frequency as well as cannabis consumption and alcohol-induced blackout episodes. Results: Results showed a statistically significant positive association between cannabis consumption and cannabis use consequences (B=0.73, p<.001), adjusting for the other variables in the model. Blackout, but not HED, was a significant moderator (B=0.19, p=.003). Discussion: The findings of this study indicate that blackout experiences amplify the relationship between cannabis use and cannabis-related consequences among college students. This underscores that blackouts not only signal a risk of problematic drinking but also exacerbate the association between cannabis use and its negative consequences. Conclusion: Findings may inform college campus interventions targeting cannabis and alcohol concurrent-users who experience alcohol-induced blackouts to reduce their additional risk for cannabis-related consequences.

Abolishing UCHL1's hydrolase activity exacerbates ischemia-induced axonal injury and functional deficits in mice.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a neuronal protein important in maintaining axonal integrity and motor function and may be important in the pathogenesis of many neurological disorders. UCHL1 may ameliorate acute injury and improve recovery after cerebral ischemia. In the current study, the hypothesis that UCHL1's hydrolase activity underlies its effect in maintaining axonal integrity and function is tested after ischemic injury. Hydrolase activity was inhibited by treatment with a UCHL1 hydrolase inhibitor or by employing knockin mice bearing a mutation in the hydrolase active site (C90A). Ischemic injury was induced by oxygen-glucose deprivation (OGD) in brain slice preparations and by transient middle cerebral artery occlusion (tMCAO) surgery in mice. Hydrolase activity inhibition increased restoration time and decreased the amplitude of evoked axonal responses in the corpus callosum after OGD. Mutation of the hydrolase active site exacerbated white matter injury as detected by SMI32 immunohistochemistry, and motor deficits as detected by beam balance and cylinder testing after tMCAO. These results demonstrate that UCHL1 hydrolase activity ameliorates white matter injury and functional deficits after acute ischemic injury and support the hypothesis that UCHL1 activity plays a significant role in preserving white matter integrity and recovery of function after cerebral ischemia.

Effects of Patient-Initiated Brief Admissions on Psychiatric Care Consumption in Borderline Personality Disorder: ARegister-Based Study.

Previous studies have reported that patients with borderline personality disorder (BPD) often have negative experiences in psychiatric inpatient care. To address this issue, a novel intervention known as patient-initiated brief admission (PIBA) has been developed. PIBA offers a constructive approach to crisis management in situations of heightened anxiety, as well as during instances of self-harm and suicidal ideation. The intervention allows patients to directly contact the psychiatric ward to initiate a brief admission lasting 1-3 days. This easily accessible care option during a crisis has the potential to prevent harm to the patient and reduce the need for prolonged hospital stays. The aim of the present study is to investigate the effects of PIBA on psychiatric care consumption among patients diagnosed with BPD. This retrospective register-based study includes data from both inpatient and outpatient care registries for patients diagnosed with BPD. Data were extracted from the National Board of Health and Welfare in Sweden. The study period encompasses 2013-2020, with the PIBA intervention occurring between 2016 and 2019. The sample included 107 patients in the PIBA group and 5659 matched controls. Data were analysed using a difference-in-differences (DiD) approach through ordinary least squares (OLS) regression and ordinal logistic regression. Throughout the 3-year follow-up, both groups exhibited a reduction in the number of days of utilisation of psychiatric inpatient care services. The DiD analysis indicated an additional decrease of 1.5 days at the 6-month mark for the PIBA group (ß = -1.436, SE = 1.531), expanding to 3 days fewer at the 12-month follow-up (ß = -3.590, SE = 3.546), although not statistically significant. For outpatient care, the PIBA group displayed an increase in the number of visits, averaging to half a visit more every 6 months (ß = 0.503, SE = 0.263) compared with the controls. Statistically significant differences were observed for two out of six measurements at the 12-month (ß = 0.960, SE = 0.456) and 18-month follow-up period (ß = 0.436, SE = 0.219). The PIBA group had a statistically significant lower odds of experiencing extended lengths of inpatient care days after the index date than the controls (OR 0.56, 95% CI: 0.44-0.72). In conclusion, PIBA was associated with a significant reduction in the length of individual hospital stays, but not in the overall number of inpatient care days. PIBA may be linked to a shift from longer inpatient care utilisation to outpatient care utilisation. These findings suggest that PIBA may reduce the risk of prolonged hospitalisations for patients who have access to the intervention. Future research should explore the impact of PIBA on healthcare costs and cost-effectiveness, both in relation to health care for the individual and cost-effectiveness in relation to recovery and health.

Alcohol's Role in Sexual Decision Making in First-Year College Women: An Event-Level Assessment.

Sexual decision making is often grounded in social scripts that can be detrimental to women's healthy relationship and sexual development during the transition to college. Little is known about the malleable decision-making processes and drinking behaviors that influence sexual behaviors from day-to-day. We examined whether women were more likely to engage in sexual behaviors on days they had higher intentions and willingness to engage in sex or drink alcohol. We also explored interactions between sex- and alcohol-related decision constructs. Eighty-two first-year college women completed 14-days of ecological momentary assessment, reporting on alcohol- and sex-related intentions and willingness (3x daily) and daily drinking and sexual behaviors. We found partial support for our hypotheses: intentions and willingness to have sex were positively associated with sex behaviors, but willingness to drink was negatively associated with sex behaviors. Heavy drinking was associated with sexual behavior, even when women indicated no prior willingness to engage in sexual behavior on those days. Findings highlight the need to address event-level variability in sexual decision making, with a particular focus on how alcohol impacts these processes. Further, the robust association between sexual intentions and behavior suggests intention setting may be a particularly useful sexual empowerment education tool.

[The shared educational assessment in the smoking cessation process]. / Le bilan éducatif partagé dans le processus de sevrage tabagique.

In the context of smoking cessation, the shared educational assessment (BEP) enables us to assess the smoker's needs, define specific objectives and set up appropriate educational workshops. This multidisciplinary approach helps smokers to maintain their smoking cessation. The BEP is the first step in the educational process, exploring the various classic dimensions of therapeutic patient education (TPE) and then defining an action plan based on the priorities identified.

Cost-effectiveness of the FindMyApps eHealth intervention vs. digital care as usual: results from a randomised controlled trial.

OBJECTIVES: Despite growing interest, the cost-effectiveness of eHealth interventions for supporting quality of life of people with dementia and their caregivers remains unclear. This study evaluated the cost-effectiveness of the FindMyApps intervention, compared to digital care-as-usual. FindMyApps aims to help people with dementia and their caregivers find and learn to use tablet apps that may support social participation and self-management of people with dementia and sense of competence of caregivers. METHOD: A randomised controlled trial (Netherlands Trial Register NL8157) was conducted, including people with mild cognitive impairment (MCI) or mild dementia and their informal caregivers (FindMyApps n = 76, digital care-as-usual n = 74). Outcomes for people with MCI/dementia were Quality-Adjusted Life-Years (QALYs), calculated from EQ-5D-5L data and the Dutch tariff for utility scores, social participation (Maastricht Social Participation Profile) and quality of life (Adult Social Care Outcomes Toolkit), and for caregivers, QALYs and sense of competence (Short Sense of Competence Questionnaire). Societal costs were calculated using data collected with the RUD-lite instrument and the Dutch costing guideline. Multiple imputation was employed to fill in missing cost and effect data. Bootstrapped multilevel models were used to estimate incremental total societal costs and incremental effects between groups which were then used to calculate Incremental Cost-Effectiveness Ratios (ICERs). Cost-effectiveness acceptability curves were estimated. RESULTS: In the FindMyApps group, caregiver SSCQ scores were significantly higher compared to care-as-usual, n = 150, mean difference = 0.75, 95% CI [0.14, 1.38]. Other outcomes did not significantly differ between groups. Total societal costs for people with dementia were not significantly different, n = 150, mean difference = €-774, 95%CI [-2.643, .,079]. Total societal costs for caregivers were significantly lower in the FindMyApps group compared to care-as-usual, n = 150, mean difference = € -392, 95% CI [-1.254, -26], largely due to lower supportive care costs, mean difference = €-252, 95% CI [-1.009, 42]. For all outcomes, the probability that FindMyApps was cost-effective at a willingness-to-pay threshold of €0 per point of improvement was 0.72 for people with dementia and 0.93 for caregivers. CONCLUSION: FindMyApps is a cost-effective intervention for supporting caregivers' sense of competence. Further implementation of FindMyApps is warranted.

Brief admission by self-referral for individuals with self-harm and suicidal ideation: a qualitative study based on focus groups exploring relatives' experiences.

PURPOSE: Brief Admission by self-referral (BA) is a standardized crisis-management intervention for individuals with self-harm and risk for suicide. This study explored relatives' experiences of BA. Relatives' perspectives may contribute to an increased understanding of the effects of BA given the relatives' role as support and informal caregivers as well as being co-sufferers. METHODS: Fourteen relatives to adults with access to BA within one Swedish region participated in focus groups analysed with reflexive thematic analysis. RESULTS: We generated themes evolving around three meaning-based concepts: access (A low threshold to a safe back-up is crucial and obstacles may easily break faith), independence (Trust in their ability with care and respect), and recovery (The rest and relational recovery we all get are needed and invaluable). CONCLUSIONS: BA brings considerable value to users and relatives, by supporting them to take care of themselves and each other. Communication and involvement of relatives may enhance users' ability to overcome obstacles to accessing BA. Implementation and adherence may be strengthened by supervision of BA staff and education of emergency care staff. Resources are needed to improve access. Mapping hurdles to BA, support through peers and targeted psychoeducation may improve recovery for BA users and their relatives.

Working through multiple crises: the experience of psychotherapists and psychoanalysts in Lebanon.

INTRODUCTION: This research explores the impact of the COVID-19 pandemic on psychotherapists' practices and their ability to maintain a framework despite a shared reality with their patients. The specific focus in this article is on the Lebanese context, which is characterized by a series of crises including economic collapse, the COVID-19 pandemic, and the Beirut blast. The objective of this study was to examine how the destabilization of the meta-frame due to crises necessitates adaptations in theoretical knowledge, practice, and setting. METHODS: We conducted a qualitative study among a population consisting of mental health professionals, which were recruited in Lebanon through associations and societies of psychologists, psychotherapists, and psychoanalysts. Data was collected using semi-structured individual interviews. The interviews were analyzed using interpretative phenomenological analysis (IPA), which allowed for a dynamic exploration of the participants' experiences. RESULTS: Our study revealed four superordinate themes: (1) The strained frontiers; (2) The cumulative traumatic reality and its impact; (3) A challenged professional identity; (4) The creativity stemming from collective trauma. CONCLUSIONS: Our results highlight the insecurity caused by external reality infiltrating the therapeutic setting. Online therapy allowed for continued work, but uncertainty about the online environment's impact on therapeutic relationships was observed. The study underscores the importance of adaptability, containment, and support for therapists navigating crises, particularly in the online setting.

Post-transplant cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil compared to anti-thymocyte globulin, calcineurin inhibitor, and methotrexate combinations as graft-versus-host disease prophylaxis post allogeneic stem cell transplantation from sibling and unrelated donors in patients with acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX. Patients in the PTCy-based group were younger (48.7 vs. 51.5 years, p = 0.024) and there was a higher frequency of patient cytomegalovirus seropositivity and female donor to male patient combination in this group (77.8% vs. 71.8%, p = 0.009 and 18.4% vs. 14.4%, p = 0.029, respectively). More patients in the PTCy-based group received reduced-intensity conditioning (51.5% vs. 41%, p < 0.0001). No differences were observed in the incidence of acute GVHD grade II-IV and III-IV (21.2% vs. 20.4%, p = 0.92 and 8.1% vs. 6%, p = 0.1) or 2-year total and extensive chronic GVHD (33.7% vs. 30%, p = 0.09 and 10.7% vs. 11.2%, p = 0.81) between the groups. In the multivariate analysis, all transplant outcomes did not differ between the groups. PTCy/CNI/MMF and ATG/CNI/MTX are alternative regimens for GVHD prophylaxis in AML patients.

Mismatched related donor allogeneic haematopoietic cell transplantation compared to other donor types for Ph+ chronic myeloid leukaemia: A retrospective analysis from the Chronic Malignancies Working Party of the EBMT.

Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.

Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation.

Lower relapse incidence with haploidentical versus matched sibling or unrelated donor hematopoietic cell transplantation for core-binding factor AML patients in CR2: A study from the Global Committee and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for core-binding factor mutated (CBF) AML patients achieving second complete remission (CR2). However, approximately 20% of patients may relapse after transplant and donor preference remains unclear. We compared in this EBMT global multicenter registry-based analysis the allo-HCT outcomes using either haploidentical (Haplo), matched siblings donors (MSD), or 10/10 matched unrelated donors (MUD). Data from 865 de novo adult CBF AML patients in CR2 receiving allo-HCT in 227 EBMT centers from 2010 to 2022 were analyzed, in which 329 MSD, 374 MUD, and 162 Haplo-HCTs were included. For the entire cohort, 503 (58%) patients were inv(16)/CBFB-MYH11 and 362 patients (42%) were t(8;21)/RUNX1-RUNX1T1 AML. On multivariate analysis, Haplo-HCT was associated with a lower Relapse Incidence (RI) compared to either MSD (hazard ratio [HR] = 0.56, 95% CI 0.32-0.97; p < .05) or MUD (HR = 0.57, 95% CI: 0.33-0.99, p < .05). No significant difference was observed among the 3 types of donors on LFS, OS and GRFS. CBF-AML with t(8;21) was associated with both higher RI (HR = 1.79, 95% CI 1.3-2.47; p < .01) and higher NRM (HR = 1.58, 95% CI 1.1-2.27; p < .01) than CBF-AML with inv(16), which led to worse LFS, OS and GRFS. To conclude, for CBF-AML patients in CR2, Haplo-HCTs were associated with a lower RI compared to MSD and MUD allo-HCTs. There was no difference on LFS, OS or GRFS. CBF AML patients with inv(16) had a better progonosis than those with t(8;21) after allo-HCT in CR2.

Revisiting the IOM Reports and Envisioning a Promising Future for Public Health.

Two public health reports from the National Academies of Sciences, Engineering, and Medicine published in 1988 and 2003 by the Institute of Medicine continue to resonate. The COVID-19 pandemic highlighted the need for a robust and adequately funded public health system that has political and public support as well as strong connections to health care and other sectors. However, a spate of recent assessments of the nation's public health infrastructure shows continuing gaps in funding, workforce, capacity, and other dimensions. There are reasons for optimism and opportunities for progress in public health in the third decade of the 21st century. There is great promise in cross-sector partnerships and in embracing the "public" in public health by building power with communities in health improvement efforts and in decision-making. (Am J Public Health. 2024;114(5):495-500. https://doi.org/10.2105/AJPH.2024.307584).

Outcomes of allogeneic haematopoietic cell transplantation for myelofibrosis in children and adolescents: the retrospective study of the EBMT Paediatric Diseases WP.

This retrospective study evaluated 35 children (median age 5.2 years; range 0.4-18) with myelofibrosis (MF), including 33 with primary myelofibrosis and 2 with secondary myelofibrosis transplanted from matched sibling donor (MSD) (n = 17) or non-MSD (n = 18) between 2000 and 2022. Conditioning was usually chemotherapy-based (n = 33) and myeloablative (n = 32). Fifteen patients received bone marrow (BM), 14 haematopoietic cells (HC) from peripheral blood (PB), and 6 from cord blood (CB). Day +100 acute GvHD II-IV incidence was significantly lower after MSD-haematopoietic cell transplantation (MSD-HCT) than after non-MSD-HCT [18.8% (4.3-41.1) vs 58.8% (31-78.6); p = 0.01]. Six-year non-relapse mortality (NRM) was 18% (7.1-32.8), relapse incidence was 15.9% (5.6-30.9), progression-free survival (PFS) was 66.1% (47-79.7), GvHD-free relapse-free survival was 50% (30.6-66.7), and overall survival (OS) was 71.1% (51.4-84). Six-year PFS and OS were significantly higher after BM transplantation compared to HCT from other sources [85.1% (52.3-96.1) vs 50.8% (26.3-71), p = 0.03, and 90.9% (50.8-98.7) vs 54% (28.1-74.2), p = 0.01, respectively], whereas NRM was significantly lower [0% vs 32% (12.3-53.9); p = 0.02]. This first multicentre study on outcomes of allogeneic HCT in children with myelofibrosis proves feasibility and curative effect of transplantation in these children, suggests that bone marrow transplantation is associated with better outcomes, and indicates the need for further studies.

Histological characterization of liver involvement in systemic mastocytosis.

BACKGROUND AND AIMS: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.

Evaluation of the applicability of GARDskin to predict skin sensitizers in extracts from medical device materials.

Biocompatibility testing of medical devices is governed by the ISO 10993 series of standards and includes evaluation of skin sensitization potential of the final product. A majority of all medical devices are tested using in vivo methods, largely due to the lack of in vitro methods validated within the applicability domain of solid materials. The GARDskin method for assessment of chemical skin sensitizers is a validated method included in the OECD Test Guideline 442E, based on evaluation of transcriptional patterns of an endpoint-specific genomic biomarker signature in a dendritic cell-like cell, following test chemical exposure. The current study aimed to evaluate the applicability of GARDskin for the purpose of testing solid materials by incorporation of extraction procedures described in ISO 10993-12:2021, as well as to demonstrate the functionality of the proposed protocols, by testing of custom-made materials spiked with sensitizing agents. It was shown that GARDskin is compatible with both polar and non-polar extraction vehicles frequently used for the purpose of medical device biological testing. Further, exploring three different material types spiked with up to four different sensitizing agents, as well as three unspiked control materials and commercial reference products, it was shown that the method correctly classified all evaluated test materials. Taken together, the data presented suggest that GARDskin may constitute a valid alternative to in vivo experimentation for the purpose of skin sensitization assessment of medical devices.

Title: Sarcopenia assessed by DXA and hand-grip dynamometer: a potential marker of damage, disability and myokines imbalance in inflammatory myopathies.

OBJECTIVES: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). METHODS: . Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors of the damage were measured. RESULTS: DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30% respectively) with a dispersion that varied widely (IQR -24.3% to + 7.8% and -51.3% to -18.9% respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, p= 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains), and blood-levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, functions impairment, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (AUC 0.71 and 0.80, respectively). CONCLUSION: DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis.