The superiority of total body irradiation (TBI)-based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)- or treosulfan (TREO)-based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TBI. This trial was registered at www.ClinicalTrials.gov as #NCT01949129.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * therapy mortality MeSH
- Busulfan * analogs & derivatives therapeutic use MeSH
- Child MeSH
- Transplantation, Homologous MeSH
- Humans MeSH
- Adolescent MeSH
- Graft vs Host Disease * etiology MeSH
- Child, Preschool MeSH
- Transplantation Conditioning * methods MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects MeSH
- Vidarabine analogs & derivatives therapeutic use administration & dosage MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- MeSH
- COVID-19 MeSH
- Pandemics prevention & control MeSH
- World Health Organization MeSH
- Vaccination MeSH
- Geographicals
- Slovakia MeSH
BACKGROUND: Globally, most people with head and neck cancers (HNCs) are diagnosed with advanced-stage disease. HNC diagnostic stage has multifactorial explanations, with the role of health system factors not yet fully investigated. METHODS: HNC centres (n = 18) from the HEADSpAcE Consortium were surveyed via a bespoke health system questionnaire covering a range of factors. Centres were compared using the least square means for the presence/absence of each health system factor to their proportion of advanced-stage HNC. RESULTS: Health system factors associated with lower proportion in advanced-stage diagnosis were formal referral triaging (14%, 95% CI-0.26, -0.03), routine monitoring of time from referral to diagnosis (16%, 95% CI-0.27, -0.05), and fully publicly funded systems (17%, 95% CI-0.29, -0.06). Several health systems factors had no routinely available data. CONCLUSIONS: Through identifying and monitoring health systems factors associated with lower proportions of advanced stage HNC, interventions could be developed, and systems redesigned, to improve early diagnosis.
- MeSH
- Benchmarking * MeSH
- Early Detection of Cancer MeSH
- Referral and Consultation statistics & numerical data MeSH
- Humans MeSH
- Head and Neck Neoplasms * pathology diagnosis MeSH
- Surveys and Questionnaires MeSH
- Neoplasm Staging MeSH
- Triage MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)-an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male-male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social-emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior. These findings advance our mechanistic understanding of the social difficulties characterizing autism.
- MeSH
- Autistic Disorder * physiopathology psychology diagnostic imaging MeSH
- Adult MeSH
- Emotions * physiology MeSH
- Interpersonal Relations * MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Young Adult MeSH
- Brain * physiopathology diagnostic imaging MeSH
- Social Behavior * MeSH
- Social Interaction * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
BackgroundThe prevalence of Alzheimer's disease (AD) is increasing, and with it comes the demand for specialized services. Current information on the institutionalization of patients with AD is limited.ObjectiveTo determine the level of institutionalization among AD patients in the facilities of the Czech Republic and the Slovak Republic.MethodsA survey of the rate of institutionalization in facilities in the Czech Republic and Slovak Republic. The survey collects data on the institutionalization of patients suffering from AD in relation to the capacity of the facilities and the prevalence of the disease. Data were collected by representative quantitative survey, during years 2019-2021.ResultsPatients with AD occupy approximately 25% of the total capacities of institutions in the Czech and Slovak Republics. The rate of institutionalization of patients with AD is estimated at 20.5% in the Czech Republic and 24% in the Slovak Republic. This is more than the estimated worldwide rate of institutionalization of people with AD (16%) but less than the estimated rate of institutionalization of these patients in high-income countries (31%).ConclusionsAs the prevalence of AD increases, so do the demands for care. If there is no increase in institutional capacity, this growth will put more pressure on home care. In order to provide specialized care to as many patients as possible, emphasis must be placed on increasing the capacity of institutions.
- MeSH
- Alzheimer Disease * epidemiology therapy MeSH
- Institutionalization * statistics & numerical data trends MeSH
- Humans MeSH
- Prevalence MeSH
- Surveys and Questionnaires MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
BACKGROUND: Pulmonary arterial hypertension (PAH) is a common complication among patients with congenital heart disease (CHD). Despite advances in PAH treatment, evidence for the benefits of PAH therapies in CHD-PAH is limited. OBJECTIVES: This analysis aimed to evaluate outcomes in patients with repaired PAH-CHD receiving an approved PAH drug. METHODS: This was a pooled analysis including CHD-PAH patients whose CHD was repaired ≥1 year prior from 3 randomized, placebo-controlled, event-driven studies: GRIPHON (NCT01106014), SERAPHIN (NCT00660179), and COMPASS-2 (NCT00303459). The primary endpoint was time to first confirmed morbidity/mortality (M/M) event. HRs with 95% CIs were determined with random effects models. RESULTS: The analysis included 1,982 patients with PAH, 177 (8.9%) with CHD-PAH. In the overall PAH cohort, the mean age was 48 and 49 years in treatment and placebo groups; 80% and 77% were female. In the CHD-PAH cohort, the mean age was 41 and 39 years; 70% and 66% were female. Overall, ≥98% in each group were World Health Organization functional class II and III at baseline. There was a significant reduction in risk of M/M events vs placebo in the overall PAH and CHD-PAH cohorts: 37% reduction in the overall PAH cohort (HR: 0.63; 95% CI: 0.52-0.77) and 50% reduction in the CHD-PAH population (HR: 0.50; 95% CI: 0.26-0.94). CONCLUSIONS: Treatment with approved PAH drugs provided a similar reduction in M/M risk in patients with repaired CHD-PAH when compared with the overall PAH population. This pooled analysis provides important evidence to guide medical management in this patient population.
- Publication type
- Journal Article MeSH
Background: The intermediate filament nestin was first described in stem and progenitor cells of neural and mesenchymal origin. Additionally, it is expressed in endothelial cells during wound healing and tumorigenesis. Thus, nestin is widely regarded as a marker for proliferative endothelium. However, little is known about its role in lymphatic endothelium. Methods: Here, we analyzed the expression of nestin in the endothelium of ten human haemangiomas and ten lymphangiomas in situ by immunohistochemistry. This study aimed to investigate the expression of nestin in haemangiomas and lymphangiomas to determine its potential role as a vascular marker. Specifically, we aimed to assess whether nestin expression is restricted to proliferating endothelial cells or also present in non-proliferative blood vessels. Results: Immunohistochemically, haemangiomas were positive for CD31 but negative for D2-40. The endothelial cells within these lesions showed a homogeneous expression of nestin. In contrast, the endothelium of lymphangiomas reacted positively for D2-40 and CD31 but did not show any nestin expression. Additionally, only a few endothelial cells of capillary haemangiomas showed a Ki-67 positivity. Conclusions: The differential expression of nestin in haemangiomas and lymphangiomas indicates a specificity of nestin for the endothelium of blood vessels. The Ki-67 negativity in the majority of the endothelial cells reveals the proliferative quiescence of these cells. These findings indicate that nestin could be used as a marker to differentiate between blood and lymphatic vessels.
- Publication type
- Journal Article MeSH
Offspring of parents with severe mental illness are at increased risk of developing psychopathology. Identifying endophenotypic markers in high-familial-risk individuals can aid in early detection and inform development of prevention strategies. Using generalized additive mixed models, we compared age trajectories of gyrification index (GI) and sulcal morphometric measures (i.e., sulcal depth, length and width) between individuals at familial risk for bipolar disorder or schizophrenia and controls. 300 T1-weighted MRI scans were obtained of 187 individuals (53 % female, age range: 8-23 years) at familial risk for bipolar disorder (n = 80, n families=55) or schizophrenia (n = 53, n families=36) and controls (n = 54, n families=33). 113 individuals underwent two scans. Globally, GI, sulcal depth and sulcal length decreased significantly with age, and sulcal width increased significantly with age in a (near-)linear manner. There were no differences between groups in age trajectories or mean values of gyrification or any of the sulcal measures. These findings suggest that, on average, young individuals at familial risk for bipolar disorder or schizophrenia have preserved developmental patterns of gyrification and sulcal morphometrics during childhood and adolescence.
- MeSH
- Bipolar Disorder * pathology MeSH
- Child MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Adolescent MeSH
- Young Adult MeSH
- Cerebral Cortex growth & development diagnostic imaging pathology anatomy & histology MeSH
- Schizophrenia * pathology diagnostic imaging genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: To evaluate the role of an anti-reflux diet in the treatment of patients with chronic cough caused by laryngopharyngeal reflux (LPR). METHODS: This prospective observational study included patients with chronic cough (lasting over 3 months) and laryngopharyngeal reflux (LPR) confirmed by hypopharyngeal-esophageal 24-h multichannel intraluminal impedance-pH monitoring (HEMII-pH), according to Dubai criteria. Participants were categorized based on cough severity using a visual analog scale (VAS) from 1 to 10. A VAS < 5 was considered to indicate mild cough, whereas a VAS ≥ 5 were considered to indicate severe cough. Patients with mild cough were treated by anti-reflux diet only, while those with severe cough received additional treatment with proton pump inhibitors (PPIs) and alginates. After 3 months, treatment effectiveness was evaluated by assessing the reduction in cough severity. RESULTS: In patients with mild cough, anti-reflux diet alone proved to be effective, yielding improvement in 83.3% of cases. Among patients with severe cough, a combination of anti-reflux diet, proton pump inhibitors (PPIs), and alginates proved was effective in 81.8% of cases. CONCLUSION: Diet alone is an effective and sufficient treatment for mild chronic cough in patients with LPR. For patients with severe chronic cough with LPT, combined anti-reflux measures are effective.
- MeSH
- Alginates therapeutic use MeSH
- Chronic Disease MeSH
- Chronic Cough MeSH
- Adult MeSH
- Proton Pump Inhibitors * therapeutic use MeSH
- Cough * etiology drug therapy MeSH
- Laryngopharyngeal Reflux * complications diet therapy drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Esophageal pH Monitoring MeSH
- Prospective Studies MeSH
- Aged MeSH
- Severity of Illness Index MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
