To improve the outcome of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients, the AIEOP-BFM ALL 2009 trial modified T-ALL stratification and treatment based on AIEOP-BFM ALL 2000 and other pediatric ALL groups' results. This report aims to describe the outcome of T-ALL patients in trial AIEOP-BFM ALL 2009 and evaluate prognostic features defined within the end of induction (EOI) therapy, for future protocols stratification and interventions. From 06/2010 to 02/2017, 872 T-ALL patients, aged 1-17, were enrolled. High risk (HR) criteria were prednisone poor response (PPR), Day 15 flow cytometry minimal residual disease (MRD) ≥ 10%, no complete remission at EOI, or polymerase chain reaction (PCR)-MRD ≥ 5 × 10-4 at end of consolidation (EOC). Three Cox regression models on event-free survival (EFS) evaluated prognostic factors. Overall, 5-year EFS and survival were 79.9% ± 1.4% and 84.9% ± 1.2% with cumulative incidence of relapse (CIR) and death of 13.0% ± 1.2% and 5.9% ± 0.8%. Five-year EFS and CIR were 86.8% ± 1.6% and 8.7% ± 1.3% in non-HR patients (n = 470); 71.9% ± 2.3% and 18.0% ± 1.9% in HR patients (n = 402). High PCR-MRD levels at EOI and EOC were prognostic in all models, with EOC-MRD ≥ 5 × 10-3 related to a hazard ratio of 6.22 (P < 0.001). When a model considered factors identified at EOI only, central nervous system (CNS)3 (hazard ratio = 2.3, P < 0.001), PPR (hazard ratio = 1.74, P = 0.02), and high EOI-MRD (hazard ratio 4.71 for ≥5 × 10-2 vs. negative, P < 0.001) significantly impacted EFS. Results of T-ALL patients in AIEOP-BFM ALL 2009 were favorable. While EOC-MRD remained the strongest prognostic predictor, PPR, CNS3 disease, and EOI-MRD showed relevant prognostic value, with CNS3 and EOI-MRD ≥ 5 × 10-2 being candidate criteria for early stratification and intervention modifications.

• Publication type
• Journal Article MeSH

OBJECTIVES: There is a paucity of validated predictors of response to anti-tumor necrosis factor (TNF) in pediatric Crohn's disease (CD). We aimed to evaluate the predictive utility of intestinal gene expression to predict response to anti-TNF in children with CD. METHODS: We enrolled children with CD before initiating anti-TNF as part of the prospective biobank of the pediatric inflammatory bowel disease Porto group of ESPGHAN. Genes potentially associated with therapeutic response were first preselected from a systematic literature review. Ribonucleic acid was extracted and sequenced from inflamed ileal biopsies of 20 children before initiating anti-TNF (13 with steroid-free remission [SFR] at 12 months, and seven with primary nonresponse [PNR]). An external validation cohort including 22 children (21 SFR, 1 PNR) was enrolled from Germany and Canada. Using maximum relevance-minimum redundancy (mRMR) methods, we constructed a support vector machine-learning model evaluated via leave-one-out cross-validation and permutation testing. RESULTS: Of 1799 studies identified in the systematic review, 24 met the inclusion criteria, reporting on 150 genes possibly associated with anti-TNF response in children or adults. In the Porto group cohort, 30 genes were associated with treatment response, of which five (TREM1, IL23R, CCL7, IL17F, and YES1) were most frequently selected. A multivariable model of these genes achieved high predictive utility (area under receiver operating characteristic curve: 0.88 [95% confidence interval: 0.69-1.0], sensitivity/specificity/positive predictive value/negative predictive value: 92%/71%/86%/83%). The same genomic signature in external validation achieved accuracy of 82% (i.e., 18/22 samples were classified correctly, including the single PNR patient). CONCLUSION: Increased expression of five genes is associated with higher rate of anti-TNF response in pediatric CD. Prospective studies are now warranted to validate these genes as biomarkers for treatment selection.

• Keywords
• RNA expression, biologics, inflammatory bowel disease,
• Publication type
• Journal Article MeSH

A metabolic disease resulting in elevated blood glucose levels, type-2 diabetes affects approximately 462 million people globally. Although its prevalence appears to be increasing, type-2 diabetes has been associated with various potentially preventable risk factors, including infectious diseases. The protozoal infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with type-2 diabetes in two previous meta-analyses. Since the publication of the last meta-analysis supporting an association between type-2 diabetes and T. gondii, several new primary studies have investigated this association. In this meta-analysis, we sought to further characterise the association between type-2 diabetes and T. gondii. We identified primary studies using PubMed, Embase, Scopus and Web of Science. Twenty-five studies met our inclusion criteria for a total of 4,639 patients with type-2 diabetes and 3,492 controls. Eighteen primary studies found a positive association between type-2 diabetes and T. gondii, whereas seven did not. Using a frequentist random-effects meta-analysis model, we found an overall summary odds ratio of 2.77 (95-percent confidence interval: 2.03-3.76), suggesting that the odds people will have type-2 diabetes is 2.7 times higher for people seropositive for T. gondii. Future studies should investigate this association in additional geographical regions and explore whether this association is due to the immunosuppressive effects of type-2 diabetes or whether T. gondii directly or indirectly affects glucose metabolism, or both.

• Keywords
• diabetes mellitus, insulin-resistant diabetes, metabolic disorder, protozoal infection, toxoplasmosis,
• MeSH
• Diabetes Mellitus, Type 2 * complications   parasitology   MeSH
• Humans MeSH
• Risk Factors MeSH
• Toxoplasma * immunology   MeSH
• Toxoplasmosis * complications   epidemiology   parasitology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

This study aimed to adapt the Burn-Specific Pain Anxiety Scale (BSPAS) for use in the Czech language and evaluate its validity and reliability. Conducted across three university hospitals in the Czech Republic-Prague, Brno, and Ostrava-from September 2022 to February 2024, the study involved 203 inpatients and outpatients from burn units who met inclusion criteria and consented to participate. The adaptation process included rigorous analysis of validity and reliability, employing language, content, and construct validity assessments. Language validity was ensured through back translation, whereas content validity was confirmed through expert evaluations. Exploratory factor analysis revealed at least a two-factor structure with satisfactory factor loading. Loading of factors to questions was consistent between BSPAS-9 and BSPAS-5. Confirmatory factor analysis further substantiated the model fit for both five- and nine-item versions (RMSEA 0.06 and 0.1 respectively). Internal consistency was assessed using item-total correlation, yielding acceptable results (range 0.63-0.82 for nine items and 0.71-0.82 for five items). Cronbach's alpha coefficients were 0.94 for the nine-item version and 0.91 for the five-item version. These findings indicate that the Czech version of the BSPAS is a valid and reliable tool for assessing pain-related anxiety in patients with burns. Additionally, we show that in our population, the information from the nine-item version is well captured by the five-item version and pain alone explains most of the variance in BSPAS scores.

• Keywords
• Anxiety, Burn-Specific Pain Anxiety Scale, Dressing changes, Pain management, Patient with burn injuries,
• MeSH
• Pain * psychology   MeSH
• Adult MeSH
• Factor Analysis, Statistical MeSH
• Middle Aged MeSH
• Humans MeSH
• Pain Measurement MeSH
• Adolescent MeSH
• Young Adult MeSH
• Burns * psychology   complications   MeSH
• Translations MeSH
• Surveys and Questionnaires MeSH
• Psychometrics MeSH
• Reproducibility of Results MeSH
• Aged MeSH
• Anxiety * diagnosis   psychology   etiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: While risk factors for children's internalizing and externalizing symptom trajectories have been widely studied, their association with parental depressive symptom trajectories has yet to be explored. METHODS: We used data from a prospective birth cohort of 2,542 Czech children and their parents. Children reported internalizing and externalizing symptoms at ages 11, 15, and 18 years. Parental depressive symptoms were assessed eight times from the prenatal period to the child's age of 11 years. Latent Class Growth Mixture Modeling identified parallel trajectories of children's symptoms. Five parental depressive symptom trajectories were adopted from previous research. RESULTS: We identified four distinct classes of children's symptom trajectories: (1) low internalizing and low externalizing (64%), (2) low internalizing and high externalizing (8%), (3) elevated internalizing and elevated externalizing (19%), and (4) high internalizing and elevated externalizing symptoms (9%). Children were more likely to experience any symptoms if their mothers had elevated depressive symptoms. High maternal and paternal depressive symptoms were associated with high internalizing and elevated externalizing symptoms in children. Constantly depressed mothers with elevated depressive symptoms in fathers had a high likelihood of any symptom trajectories in children. Other strong predictors of children's symptom trajectories included parental relationship status (e.g., divorce), prior abortion, as well as children's sex, urban versus rural residence, stressful life events, and self-esteem. CONCLUSIONS: Parents' and children's mental health trajectories are interconnected. Given the strong influence of parental relationship dynamics on both parental and child mental health, interventions should prioritize mitigating relationship strains to support family well-being.

• Keywords
• latent trajectories, mental health, parallel processes, relationship maintenance,
• MeSH
• Behavioral Symptoms * epidemiology   MeSH
• Depression * psychology   epidemiology   MeSH
• Child of Impaired Parents * psychology   statistics & numerical data   MeSH
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Prospective Studies MeSH
• Risk Factors MeSH
• Parents * psychology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH

The UPPS-P Impulsive Behavior Model and the various psychometric instruments developed and validated based on this model are well established in clinical and research settings. However, evidence regarding the psychometric validity, reliability, and equivalence across multiple countries of residence, languages, or gender identities, including gender-diverse individuals, is lacking to date. Using data from the International Sex Survey (N = 82,243), confirmatory factor analyses and measurement invariance analyses were performed on the preestablished five-factor structure of the 20-item short version of the UPPS-P Impulsive Behavior Scale to examine whether (a) psychometric validity and reliability and (b) psychometric equivalence hold across 34 country-of-residence-related, 22 language-related, and three gender-identity-related groups. The results of the present study extend the latter psychometric instrument's well-established relevance to 26 countries, 13 languages, and three gender identities. Most notably, psychometric validity and reliability were evidenced across nine novel translations included in the present study (i.e., Croatian, English, German, Hebrew, Korean, Macedonian, Polish, Portuguese-Portugal, and Spanish-Latin American) and psychometric equivalence was evidenced across all three gender identities included in the present study (i.e., women, men, and gender-diverse individuals).

• Keywords
• International Sex Survey, UPPS-P Impulsive Behavior Scale, confirmatory factor analysis, impulsive behaviors, measurement invariance analysis,
• MeSH
• Adult MeSH
• Factor Analysis, Statistical MeSH
• Gender Identity * MeSH
• Impulsive Behavior * MeSH
• Language MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Surveys and Questionnaires MeSH
• Psychometrics MeSH
• Reproducibility of Results MeSH
• Cross-Cultural Comparison MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Validation Study MeSH

Climate change is accelerating the melting of glaciers to create new habitats colonized by pioneer organisms. Lichens are adapted to extreme conditions and, together with cyanobacteria and algae, are generally among the first organisms to appear in primary succession. The exact mechanism of lichen community formation and the factors influencing species turnover are still poorly understood. The aim was to determine the time zones of succession of terricolous and saxicolous species after glacier retreat, and to identify common ecological traits among pioneer species, including thallus type. Additionally, lichen species were categorized into time periods based on their colonization rates. Finally, differences among dated plots in the glacier forelands of Midtdalsbreen (Norway) and Storglaciären (Sweden) were compared. Taxon: Lichens. Location: Arctic. A total of 27 plots (135 subplots) were delineated across five successional age classes (9-264 years postglaciation). Lichen abundances and environmental variables (e.g., orientation, substrate composition) were recorded. Canonical correspondence analysis (CCA) and detrended correspondence analysis (DCA) were used to analyze species composition gradients and the effect of successional age. Monte Carlo permutation tests were performed to determine statistical significance (499 permutations). Lichen species richness increased rapidly in the early succession (15-25 years), but stagnated or slightly declined in older stages (> 100 years), probably due to competitive displacement. Early successional pioneer species included Stereocaulon alpinum, Cetraria islandica, and Flavocetraria nivalis-fruticose lichens that disperse easily by wind through thallus fragments. Late successional species, such as Arctoparmelia centrifuga and Fuscidea kochiana, thrived under stabilized and nutrient-enriched conditions. CCA showed that successional age explained 12.9% of the variability in species composition, whereas geographic differences contributed 7.9%. Species turnover was influenced by substrate characteristics (fine-particle sediment vs. coarse rocky substrate), competition, and erosion, which was still shaped by environmental stability. Lichen succession follows the expected pattern, primarily shaped by terrain microtopography, climate, and substrate type. To refine the successional dynamics of lichen communities and other groups of organisms involved in the colonization of newly deglaciated habitats, more long-term studies from different regions will be needed.

• Keywords
• Arctic, Scandinavia, biocrust, climate warming, glaciers, lichen, species distribution model, succession, tundra,
• Publication type
• Journal Article MeSH

BACKGROUND: There is a paucity of data on treatment outcomes following stereotactic radiosurgery (SRS) for brain metastases from sarcoma primaries. METHODS: The International Radiosurgery Research Foundation member-sites were queried for patients with brain metastases from sarcoma primaries treated with SRS. Overall survival (OS) and local control (LC) were calculated via Kaplan-Meier analysis. Univariate analyses examined prognostic factors associated with LC and OS via log-rank t-tests and multivariate analyses (MVA) via Cox proportional hazards model. RESULTS: A total of 146 patients with 309 brain metastases were identified. Two-hundred and thirty lesions were treated with single-fraction SRS with a median dose of 20 Gy (15-24 Gy). Ninety-five patients had extracranial metastases, including 75 oligometastatic patients. One- and 2-year OS and LC rates were 47.7% and 37.3%, and 78.3% and 62.2%, respectively. On univariate analyses, superior 1-year OS was noted among leiomyosarcomas (69.7% vs. 42.6%; p = .02) with poorer outcomes among pleomorphic histologies (10.5% vs. 50.7%; p = .002). Pleomorphic histologies were associated with poorer OS on MVA (hazard ratio [HR], 3.13; p = .006). On MVA, LC was inferior among patients of age ≥45 years (HR, 3.78; p < .001) and superior among leiomyosarcomas (HR, 0.31; p = .03). OS was prognosticated based on adverse factors (ie, nonleiomyosarcoma histology and progressive extracranial metastases). Two-year OS for patients with and without adverse features were 78.6% and 31.5%, respectively. CONCLUSIONS: LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age <45 years. OS was driven by nonleiomyosarcoma histology and the presence of progressive extracranial disease.

• Keywords
• brain metastases, local control, overall survival, sarcoma primary, stereotactic radiosurgery,
• MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Brain Neoplasms * secondary   radiotherapy   mortality   surgery   MeSH
• Prognosis MeSH
• Radiosurgery * methods   MeSH
• Retrospective Studies MeSH
• Sarcoma * pathology   mortality   radiotherapy   secondary   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

PURPOSE: Revision total hip arthroplasty (rTHA) is an increasingly common procedure due to the growing number of primary total hip arthroplasties (THAs) performed worldwide. This study evaluates the long-term implant survival, functional outcomes, and radiographic performance of cemented femoral stem (Beznoska s.r.o., Kladno, Czechia) in rTHA. METHODS: A retrospective analysis was conducted on 183 patients who underwent rTHA with cemented stem between March 2012 and December 2023. The mean follow-up duration was 71.26(± 39.31) months. Implant survival was analyzed using Kaplan-Meier survival estimates, and failure modes were assessed. Radiographic changes were classified using the Gruen Zones system. Functional outcomes were evaluated using the Harris Hip Score (HHS). Cox proportional hazard models were applied to identify prognostic factors influencing implant survival. RESULTS: The five-year implant survival rate was 98.1%, declining to 83.9% at twelve years. The overall failure rate was 3.83%, with periprosthetic infection (4 cases) being the most common cause, followed by aseptic loosening (2 cases). Radiographic changes were observed in 24.03% of cases, predominantly in Gruen Zones 2, 6, and 1. Functional outcomes were favorable, with a mean HHS of 81.28(± 5.74), comparable to outcomes reported for uncemented revision stems. Age, stem diameter, and stem length did not significantly impact implant survival. CONCLUSION: The cemented stem demonstrated favourable long-term survival, with high implant retention rates. Functional outcomes indicated overall satisfactory performance. Radiographic evaluation revealed localized changes around the implant, predominantly in Gruen Zones 2, 6, and 1. Implant failure was relatively rare, with periprosthetic infection being the most common cause.

• Keywords
• Cemented femoral stem, Harris hip score, Implant survival, Radiographic assessment, Revision total hip arthroplasty,
• MeSH
• Cementation MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Bone Cements MeSH
• Hip Joint diagnostic imaging   surgery   MeSH
• Hip Prosthesis * adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Arthroplasty, Replacement, Hip * methods   instrumentation   adverse effects   MeSH
• Prosthesis Design MeSH
• Radiography MeSH
• Reoperation * MeSH
• Retrospective Studies MeSH
• Prosthesis Failure * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bone Cements MeSH

PURPOSE: Mutations or silencing of the von Hippel-Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in the oncogenesis of ∼50% of patients with clear-cell renal cell carcinoma (ccRCC) but has been considered "undruggable." DFF332, an orally administered novel allosteric inhibitor of HIF-2α, showed dose-dependent antitumor efficacy in preclinical models of ccRCC. PATIENTS AND METHODS: This first-in-human study evaluated the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of DFF332 in patients with heavily pretreated advanced ccRCC. Preliminary data from the dose escalation of DFF332 monotherapy, administered orally at 50 or 100 mg weekly or 25, 50, 100, or 150 mg once daily in 28-day treatment cycles, are reported. RESULTS: As of January 15, 2024, 40 patients (median age, 62.5 years) received DFF332 for a median duration of 12.1 weeks. Overall, two patients (5%) achieved a partial response, and 19 (48%) achieved stable disease as the best overall response. DFF332 showed a favorable safety profile, with treatment-related adverse events occurring in 25 patients (63%). Only five patients (13%) experienced treatment-related anemia, and no hypoxia was observed. The only serious treatment-related adverse event, hypertension, was reported in one patient. The maximum tolerated dose was not reached. CONCLUSIONS: Although clinical responses were limited in the doses evaluated, dose exploration halted prematurely, making it difficult to draw definitive conclusions about the efficacy of DFF332. Further investigation is required to establish a recommended dose regimen, assess its efficacy and safety, and evaluate its full potential as a partner in combination studies.

• MeSH
• Adult MeSH
• Carcinoma, Renal Cell * drug therapy   pathology   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Maximum Tolerated Dose MeSH
• Kidney Neoplasms * drug therapy   pathology   MeSH
• Antineoplastic Agents * administration & dosage   adverse effects   pharmacokinetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Basic Helix-Loop-Helix Transcription Factors * antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase I MeSH
• Names of Substances
• endothelial PAS domain-containing protein 1 MeSH Browser
• Antineoplastic Agents * MeSH
• Basic Helix-Loop-Helix Transcription Factors * MeSH